Trial Outcomes & Findings for Quad Shot Radiotherapy in Combination With Immune Checkpoint Inhibition (NCT NCT04454489)
NCT ID: NCT04454489
Last Updated: 2025-11-19
Results Overview
Overall response will be measured according to RECIST 1.1 criteria to determine the percentage of participants with either a partial or complete response and the corresponding 95% Clopper-Pearson exact confidence interval. The best overall response is the best response recorded from the start of the treatment across all time points. COMPLETE RESPONSE: Disappearance (or decrease to the point at which measurement is not possible) of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (the sum may not be "0" if there are target nodes) PARTIAL RESPONSE: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
Up to 2 years
Results posted on
2025-11-19
Participant Flow
Participant milestones
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
2
|
|
Overall Study
NOT COMPLETED
|
18
|
Reasons for withdrawal
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Overall Study
Disease progression
|
12
|
|
Overall Study
Death
|
4
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Quad Shot Radiotherapy in Combination With Immune Checkpoint Inhibition
Baseline characteristics by cohort
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=21 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=39 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=39 Participants
|
|
Age, Continuous
|
64 years
n=39 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Caucasian (White)
|
16 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · African American (Black)
|
4 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Hispanic
|
1 Participants
n=39 Participants
|
|
Region of Enrollment
United States
|
21 participants
n=39 Participants
|
|
Primary Cancer Site
Pharynx
|
7 Participants
n=39 Participants
|
|
Primary Cancer Site
Larynx
|
6 Participants
n=39 Participants
|
|
Primary Cancer Site
Oral Cavity
|
7 Participants
n=39 Participants
|
|
Primary Cancer Site
R Temporal Fossa
|
1 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Up to 2 yearsPopulation: Five of the patients who started treatment were not evaluable for response. The number entered below is the percentage with a complete or partial response. A 95% Clopper Pearson exact confidence interval on the rate is reported.
Overall response will be measured according to RECIST 1.1 criteria to determine the percentage of participants with either a partial or complete response and the corresponding 95% Clopper-Pearson exact confidence interval. The best overall response is the best response recorded from the start of the treatment across all time points. COMPLETE RESPONSE: Disappearance (or decrease to the point at which measurement is not possible) of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (the sum may not be "0" if there are target nodes) PARTIAL RESPONSE: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=15 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Overall Response -
|
40.0 percentage of participants
Interval 16.3 to 67.7
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Five of the patients who started treatment were not evaluable for response. The number entered below is the percentage with a complete or partial response. A 95% Clopper Pearson exact confidence interval on the rate is reported.
Response rate will be measured as the following: Complete: Disappearance (or decrease to the point at which measurement is not possible) of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial: At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease: Greater than 20% increase in the sum of the longest diameters (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir. When sum becomes very small, increases within measurement error (2-3 mm) can lead to 20% increase. Stable Disease: Greater than 20% increase in the sum of the longest diameters (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir. When sum becomes very small, increases within measurement error (2-3 mm) can lead to 20% increase.
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=15 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Response Rate in the Target Lesions
|
40.0 percentage of evaluable patients
Interval 16.3 to 67.7
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Five of the patients who started treatment were not evaluable for response. The number entered below is the percentage with a complete or partial response. A 95% Clopper Pearson exact confidence interval on the rate is reported.
Response rate will be measured using RECIST 1.1: Complete: Disappearance (or decrease to the point at which measurement is not possible) of all non-target lesions. All lymph nodes must be non-pathological in size (\< 10 mm short axis). Partial: Non-complete response/Non-progressive disease: Persistence of 1 or more non-target lesion(s). Progressive Disease: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Stable Disease: Greater than 20% increase in the sum of the longest diameters (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir. When sum becomes very small, increases within measurement error (2-3 mm) can lead to 20% increase.
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=15 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Response Rate in the Non-Target Lesions
|
10 percentage of evaluable patients
Interval 0.3 to 44.5
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Six patients had either a complete or partial response.
For the duration of response, among participants investigators will estimate both the mean duration and the corresponding 95% confidence intervals for the mean and inter-quartile range for the median. The duration of response at the target lesion will be defined as the duration from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date of recurrent or progressive disease.
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=6 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Duration of Response at the Target Lesions - Mean Measurement
|
11.6 months
Interval 3.89 to 19.31
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Six evaluable patients had a complete or partial response.
The duration of response at the target lesion(s) will be defined as the duration from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date of recurrent or progressive disease. For the duration of response, among participants investigators will estimate the median duration and the corresponding 95% confidence intervals for the mean and inter-quartile range for the median. Target Lesions: COMPLETE RESPONSE: Disappearance (or decrease to the point at which measurement is not possible) of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (the sum may not be "0" if there are target nodes) PARTIAL RESPONSE: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=6 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Duration of Response at the Target Lesions - Median Measurement
|
9.44 months
Interval 4.37 to 22.98
|
SECONDARY outcome
Timeframe: Up to 2 years.Population: 20 patients received at least one cycle of therapy.
For progression-free survival investigators will estimate Kaplan Meier survival curves and the median time to progression-free survival, as well as survival rates at 6 months and 1 year post treatment. Progression-Free Survival is defined as the duration of time from registration to the time of progression, death, or date of last contact; those lost to follow-up will be censored.
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=20 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Progression-Free Survival
|
9.2 months
Interval 3.4 to 17.2
|
SECONDARY outcome
Timeframe: Up to 2 years.Population: 20 patients received at least one cycle of therapy.
For progression-free survival investigators will estimate Kaplan Meier survival curves and the median time to progression-free survival, as well as survival rates at 6 months and 1 year post treatment. Progression-Free Survival is defined as the duration of time from registration to the time of progression, death, or date of last contact; those lost to follow-up will be censored.
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=20 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Progression-Free Survival - Survival Rate Percentages
12 months survival
|
7 Participants
|
|
Progression-Free Survival - Survival Rate Percentages
6 months survival
|
12 Participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: 20 patients received at least one cycle of therapy.
For time to event measure of overall survival investigators will estimate Kaplan Meier survival curves and the median time to overall survival, as well as survival rates at 6 months and 1 year post treatment. Overall Survival is defined as the duration of time from registration to date of death or date of last contact; those lost to follow-up will be censored.
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=20 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Overall Survival - Months
|
14.9 months
Interval 4.9 to 25.8
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: 20 patients received at least one cycle of therapy.The 6-month survival rate was 69.6%; the 12-month survival rate was 51.4%
For time to event measure of overall survival investigators will estimate Kaplan Meier survival curves and the median time to overall survival, as well as survival rates at 6 months and 1 year post treatment. Overall Survival is defined as the duration of time from registration to date of death or date of last contact; those lost to follow-up will be censored.
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=20 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Overall Survival - Survival Rate Percentages
6 months
|
14 Participants
|
|
Overall Survival - Survival Rate Percentages
12 months
|
10 Participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: For evaluable patients, the percentage of patients with the listed adverse event is given below with a 95% exact confidence interval.
Tolerability of intervention will be assessed using Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Event (PRO CTCAE). Investigators will estimate the percentage of patients with different adverse events using a 95% Clopper Pearson exact confidence level. Listed adverse events were grade 3+ and deemed at least possibly related to therapy.
Outcome measures
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=15 Participants
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Weight Loss
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Leukocytosis
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Dysphagia
|
27 percentage of evaluable patients
Interval 8.0 to 55.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Abdominal Pain
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Dry Mouth
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Nausea
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Fatigue
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Infection
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Injury or poisoning
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Bullous Pemphigoid
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Pruritus
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
|
Tolerability - Adverse Events Assessed Using PRO-CTCAE Version 5.0
Rash Maculo-papular
|
7 percentage of evaluable patients
Interval 0.0 to 32.0
|
Adverse Events
Quad-shot Palliative Radiotherapy and Immunotherapy
Serious events: 15 serious events
Other events: 20 other events
Deaths: 13 deaths
Serious adverse events
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=20 participants at risk
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Eye disorders
Floaters
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Abdominal Pain
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Colonic perforation
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Dysphagia
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Oral hemorrhage
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
General disorders
Death
|
15.0%
3/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
General disorders
Disease progression
|
15.0%
3/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Infections and infestations
Infections and Infestations
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Injury, poisoning and procedural complications
Tracheostomy site bleeding
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
Weight Loss
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor Hemorrhage
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Nervous system disorders
Facial muscle weakness
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Nervous system disorders
Paresthesia
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Nervous system disorders
Stroke
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Nervous system disorders
Vasovagal Reaction
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Aspiration
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Skin and subcutaneous tissue disorders
Bullous (Dermatitis) Pemphigoid
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Vascular disorders
Thromboembolic Event
|
5.0%
1/20 • Number of events 1 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
Other adverse events
| Measure |
Quad-shot Palliative Radiotherapy and Immunotherapy
n=20 participants at risk
Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
Pembrolizumab (immunotherapy): Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
Quad-shot palliative radiotherapy: - Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days.
* All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3.
* Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist.
Therefore, the total prescription dose will be:
* 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle)
* 19.6 Gy in 8 fractions for those that complete 2 cycles
* 44.4 Gy in 12 fractions for those that complete 3 cycles
|
|---|---|
|
Cardiac disorders
Bradycardia
|
10.0%
2/20 • Number of events 4 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Cardiac disorders
Tachycardia
|
25.0%
5/20 • Number of events 7 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Ear and labyrinth disorders
Ear pain
|
15.0%
3/20 • Number of events 8 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Ear and labyrinth disorders
Hearing impairment
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Endocrine disorders
Hypothyroidism
|
25.0%
5/20 • Number of events 7 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Eye disorders
Dry eye
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
4/20 • Number of events 7 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Constipation
|
10.0%
2/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
5/20 • Number of events 7 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Dry mouth
|
75.0%
15/20 • Number of events 24 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Dysphagia
|
50.0%
10/20 • Number of events 14 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
GERD
|
20.0%
4/20 • Number of events 5 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Mucositis
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Nausea
|
25.0%
5/20 • Number of events 13 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Oral pain
|
20.0%
4/20 • Number of events 4 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Swallowing difficulties
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Gastrointestinal disorders
Vomiting
|
15.0%
3/20 • Number of events 5 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
General disorders
Edema of limbs
|
30.0%
6/20 • Number of events 8 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
General disorders
Fatigue
|
80.0%
16/20 • Number of events 30 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Infections and infestations
Thrush
|
15.0%
3/20 • Number of events 4 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
ALT increase
|
10.0%
2/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
AST increase
|
15.0%
3/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
Alkaline Phosphatase increase
|
20.0%
4/20 • Number of events 5 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
Creatinine increase
|
10.0%
2/20 • Number of events 7 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
Lipase increase
|
20.0%
4/20 • Number of events 7 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
Lymphocyte count decrease
|
80.0%
16/20 • Number of events 37 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
Serum amylase increased
|
20.0%
4/20 • Number of events 5 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
TSH increase
|
35.0%
7/20 • Number of events 7 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
WBC decrease
|
10.0%
2/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Investigations
Weight loss
|
45.0%
9/20 • Number of events 14 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Anorexia
|
20.0%
4/20 • Number of events 4 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
70.0%
14/20 • Number of events 27 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
20.0%
4/20 • Number of events 10 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
35.0%
7/20 • Number of events 13 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
10.0%
2/20 • Number of events 7 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
25.0%
5/20 • Number of events 10 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
15.0%
3/20 • Number of events 8 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
55.0%
11/20 • Number of events 16 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
15.0%
3/20 • Number of events 6 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
2/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
10.0%
2/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
15.0%
3/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
15.0%
3/20 • Number of events 4 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
15.0%
3/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Blood and lymphatic system disorders
Eosinophilia
|
25.0%
5/20 • Number of events 10 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Blood and lymphatic system disorders
Leukocytosis
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Blood and lymphatic system disorders
Low Hemoglobin
|
15.0%
3/20 • Number of events 5 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Blood and lymphatic system disorders
Anemia
|
65.0%
13/20 • Number of events 24 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Parethesia
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
45.0%
9/20 • Number of events 15 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Nervous system disorders
Dizziness
|
10.0%
2/20 • Number of events 4 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Nervous system disorders
Dysgeusia
|
30.0%
6/20 • Number of events 11 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Nervous system disorders
Dysphasia
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Nervous system disorders
Headaches
|
15.0%
3/20 • Number of events 4 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Psychiatric disorders
Depression
|
15.0%
3/20 • Number of events 5 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Psychiatric disorders
Insomnia
|
15.0%
3/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Renal and urinary disorders
Chronis Kidney disease
|
15.0%
3/20 • Number of events 5 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
4/20 • Number of events 7 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
15.0%
3/20 • Number of events 5 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
35.0%
7/20 • Number of events 9 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
20.0%
4/20 • Number of events 5 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
25.0%
5/20 • Number of events 6 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
15.0%
3/20 • Number of events 4 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Skin and subcutaneous tissue disorders
Macupapular rash
|
15.0%
3/20 • Number of events 12 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
50.0%
10/20 • Number of events 18 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Vascular disorders
Hot flashes
|
10.0%
2/20 • Number of events 2 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Vascular disorders
Hypertension
|
60.0%
12/20 • Number of events 37 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Vascular disorders
Hypotension
|
15.0%
3/20 • Number of events 4 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
|
Vascular disorders
Lymphedema
|
10.0%
2/20 • Number of events 3 • Adverse events were recorded with each treatment cycle, up to 2 years.
|
Additional Information
Principal Investigator
Wake Forest Baptist Comprehensive Cancer Center
Phone: 336 -713-5440
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place