Trial Outcomes & Findings for Study of Combined Ionizing Radiation and Ipilimumab in Metastatic Non-small Cell Lung Cancer (NSCLC) (NCT NCT02221739)
NCT ID: NCT02221739
Last Updated: 2020-05-11
Results Overview
Tumor Response will be evaluated using the irRC best response (Partial Response (PR) + Complete Response (CR)). Modified WHO criteria will be used for measurement of tumors. The irradiated lesion will be excluded from the assessment of response.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
39 participants
Primary outcome timeframe
3 weeks - 6 months post treatment
Results posted on
2020-05-11
Participant Flow
Participant milestones
| Measure |
Ipilimumab + Radiotherapy
Patients receive ipilimumab (Ipi) 3mg/kg i.v. over 90 minutes, within 24 hours of starting radiotherapy (RT) to the biopsied lesion, 6 Gy x5, later changed to 9.5 Gy x3 (conformally or by intensity modulated RT (IMRT) with image guidance to maximally spare normal tissue). Ipilimumab is repeated on days 22, 43 (for patients who consent to the first biopsy), and 64. Repeat biopsy is performed between day 22-29, and patients are re-imaged between day 81-88 and evaluated for response (defined as an objective response by irRC of the measurable metastatic sites outside the radiation field).
Ipilimumab
Radiotherapy (IMRT or 3-D CRT)
|
|---|---|
|
Overall Study
STARTED
|
39
|
|
Overall Study
COMPLETED
|
21
|
|
Overall Study
NOT COMPLETED
|
18
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Ipilimumab + Radiotherapy
n=39 Participants
Patients receive ipilimumab (Ipi) 3mg/kg i.v. over 90 minutes, within 24 hours of starting radiotherapy (RT) to the biopsied lesion, 6 Gy x5, later changed to 9.5 Gy x3 (conformally or by intensity modulated RT (IMRT) with image guidance to maximally spare normal tissue). Ipilimumab is repeated on days 22, 43 (for patients who consent to the first biopsy), and 64. Repeat biopsy is performed between day 22-29, and patients are re-imaged between day 81-88 and evaluated for response (defined as an objective response by irRC of the measurable metastatic sites outside the radiation field).
Ipilimumab
Radiotherapy (IMRT or 3-D CRT)
|
|---|---|
|
Age, Customized
Age
|
68 years
n=39 Participants
|
|
Sex: Female, Male
Gender · Female
|
23 Participants
n=39 Participants
|
|
Sex: Female, Male
Gender · Male
|
16 Participants
n=39 Participants
|
|
Region of Enrollment
United States
|
39 Participants
n=39 Participants
|
|
Histology
Adenocarcinoma
|
34 Participants
n=39 Participants
|
|
Histology
Squamous Cell Carcinoma
|
3 Participants
n=39 Participants
|
|
Histology
Sarcomatoid
|
1 Participants
n=39 Participants
|
|
Histology
Neuroendocrine
|
1 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: 3 weeks - 6 months post treatmentTumor Response will be evaluated using the irRC best response (Partial Response (PR) + Complete Response (CR)). Modified WHO criteria will be used for measurement of tumors. The irradiated lesion will be excluded from the assessment of response.
Outcome measures
| Measure |
Ipilimumab + Radiotherapy
n=21 Participants
Patients receive ipilimumab (Ipi) 3mg/kg i.v. over 90 minutes, within 24 hours of starting radiotherapy (RT) to the biopsied lesion, 6 Gy x5, later changed to 9.5 Gy x3 (conformally or by intensity modulated RT (IMRT) with image guidance to maximally spare normal tissue). Ipilimumab is repeated on days 22, 43 (for patients who consent to the first biopsy), and 64. Repeat biopsy is performed between day 22-29, and patients are re-imaged between day 81-88 and evaluated for response (defined as an objective response by irRC of the measurable metastatic sites outside the radiation field).
Ipilimumab
Radiotherapy (IMRT or 3-D CRT)
|
|---|---|
|
Therapeutic Efficacy of Anti-CTLA-4 mAb and Concurrent Local RT in NSCLC Patients With Metastatic Disease.
|
7 Participants
|
SECONDARY outcome
Timeframe: 3 weeks - 6 months post-treatmentThe study uses a comprehensive approach to analyze immunological changes that reflect both local and systemic responses, and investigate both general immune activation as well as tumor antigen-specific T- and B-cell responses. The activity of anti-CTLA-1 mAb is thought to be mainly dependent on modulating the quantity and quality of T-cells in cancer patients. A highly extensive analysis of the Cluster of differentiation 4 + (CD4+) and cluster of differentiation 8 + (CD8+) T-cell subsets will be characterized by multi-color flow Cytometry. To facilitate these analyses, serial blood samples will be collected for serum and peripheral blood mononuclear cells (PBMC) at different time points, where, a part of these samples will be used for DNA/RNA extraction. Optional tissue biopsies will be obtained from consenting patients.Tumor tissue will be tested for expression of seven antigens frequently expressed in NSCLC.
Outcome measures
| Measure |
Ipilimumab + Radiotherapy
n=21 Participants
Patients receive ipilimumab (Ipi) 3mg/kg i.v. over 90 minutes, within 24 hours of starting radiotherapy (RT) to the biopsied lesion, 6 Gy x5, later changed to 9.5 Gy x3 (conformally or by intensity modulated RT (IMRT) with image guidance to maximally spare normal tissue). Ipilimumab is repeated on days 22, 43 (for patients who consent to the first biopsy), and 64. Repeat biopsy is performed between day 22-29, and patients are re-imaged between day 81-88 and evaluated for response (defined as an objective response by irRC of the measurable metastatic sites outside the radiation field).
Ipilimumab
Radiotherapy (IMRT or 3-D CRT)
|
|---|---|
|
Number pf Patients With Objective Radioactive Responses to Measure the Effects of RT and Anti-CTLA-4 mAb on Development of Anti-tumor Immunity Measured by T Cell Clone Frequency
Objective Radiographic Responses
|
7 Participants
|
|
Number pf Patients With Objective Radioactive Responses to Measure the Effects of RT and Anti-CTLA-4 mAb on Development of Anti-tumor Immunity Measured by T Cell Clone Frequency
Complete Responses (CR)
|
2 Participants
|
|
Number pf Patients With Objective Radioactive Responses to Measure the Effects of RT and Anti-CTLA-4 mAb on Development of Anti-tumor Immunity Measured by T Cell Clone Frequency
Partial Responses (PR)
|
5 Participants
|
Adverse Events
Ipilimumab + Radiotherapy
Serious events: 19 serious events
Other events: 39 other events
Deaths: 17 deaths
Serious adverse events
| Measure |
Ipilimumab + Radiotherapy
n=39 participants at risk
Patients receive ipilimumab (Ipi) 3mg/kg i.v. over 90 minutes, within 24 hours of starting radiotherapy (RT) to the biopsied lesion, 6 Gy x5, later changed to 9.5 Gy x3 (conformally or by intensity modulated RT (IMRT) with image guidance to maximally spare normal tissue). Ipilimumab is repeated on days 22, 43 (for patients who consent to the first biopsy), and 64. Repeat biopsy is performed between day 22-29, and patients are re-imaged between day 81-88 and evaluated for response (defined as an objective response by irRC of the measurable metastatic sites outside the radiation field).
Ipilimumab
Radiotherapy (IMRT or 3-D CRT)
|
|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death
|
48.7%
19/39 • Number of events 19 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
Other adverse events
| Measure |
Ipilimumab + Radiotherapy
n=39 participants at risk
Patients receive ipilimumab (Ipi) 3mg/kg i.v. over 90 minutes, within 24 hours of starting radiotherapy (RT) to the biopsied lesion, 6 Gy x5, later changed to 9.5 Gy x3 (conformally or by intensity modulated RT (IMRT) with image guidance to maximally spare normal tissue). Ipilimumab is repeated on days 22, 43 (for patients who consent to the first biopsy), and 64. Repeat biopsy is performed between day 22-29, and patients are re-imaged between day 81-88 and evaluated for response (defined as an objective response by irRC of the measurable metastatic sites outside the radiation field).
Ipilimumab
Radiotherapy (IMRT or 3-D CRT)
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
7.7%
3/39 • Number of events 3 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Renal and urinary disorders
Acute Kidney Injury
|
5.1%
2/39 • Number of events 2 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Hepatobiliary disorders
Alkaline Phosphotase
|
15.4%
6/39 • Number of events 6 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Hepatobiliary disorders
ALT
|
15.4%
6/39 • Number of events 6 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Blood and lymphatic system disorders
Anemia
|
15.4%
6/39 • Number of events 6 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Psychiatric disorders
Anorexia
|
38.5%
15/39 • Number of events 15 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Hepatobiliary disorders
AST
|
12.8%
5/39 • Number of events 5 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Cardiac disorders
Cardiac arrest
|
5.1%
2/39 • Number of events 2 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
General disorders
Cough
|
7.7%
3/39 • Number of events 3 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
General disorders
Dehydration
|
7.7%
3/39 • Number of events 3 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Gastrointestinal disorders
Diarrhea
|
28.2%
11/39 • Number of events 11 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Musculoskeletal and connective tissue disorders
Dry Skin
|
5.1%
2/39 • Number of events 2 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Psychiatric disorders
Dyspnea
|
23.1%
9/39 • Number of events 9 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Renal and urinary disorders
Edema
|
10.3%
4/39 • Number of events 4 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Psychiatric disorders
Fatigue
|
76.9%
30/39 • Number of events 30 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Psychiatric disorders
Fever
|
7.7%
3/39 • Number of events 3 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Renal and urinary disorders
Hyperglycemia
|
5.1%
2/39 • Number of events 2 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Endocrine disorders
Hyperthyroid
|
5.1%
2/39 • Number of events 2 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Blood and lymphatic system disorders
Hyponatremia
|
10.3%
4/39 • Number of events 4 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Endocrine disorders
Hypothyroid
|
5.1%
2/39 • Number of events 2 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Blood and lymphatic system disorders
Hypoxia
|
5.1%
2/39 • Number of events 2 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.1%
2/39 • Number of events 2 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
General disorders
Nausea
|
12.8%
5/39 • Number of events 5 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
General disorders
Peripheral neuropathy
|
7.7%
3/39 • Number of events 3 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
General disorders
Pruritis
|
43.6%
17/39 • Number of events 17 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
General disorders
Rash
|
33.3%
13/39 • Number of events 13 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
General disorders
Skin ulceration
|
5.1%
2/39 • Number of events 2 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
|
General disorders
Tachycardia
|
7.7%
3/39 • Number of events 3 • 60 Months
Adverse events as related to Ipilimumab or radiotherapy treatment. Grade of adverse event is shown: 1 - mild, 2 - moderate, 3 - Severe or medically significant but not immediately life-threatening, 4 - Life-threatening consequences, and 5 - Death related to AE.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place