Trial Outcomes & Findings for High or Standard Intensity Radiation Therapy After Gemcitabine Hydrochloride and Nab-paclitaxel in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery (NCT NCT01921751)

NCT ID: NCT01921751

Last Updated: 2018-07-13

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

From randomization until last follow-up. Analysis was to occur after a total of 140 deaths were reported within the pairing of each radiation arm with the chemotherapy alone arm. Maximum follow-up at time of study termination was 8.3 months.

Results posted on

2018-07-13

Participant Flow

Patients were registered and received 3 cycles of Gemcitabine/nab-Paclitaxel and then had central SMAD4 testing done. Patients then had a CT/MRI of their abdomen/pelvis for restaging. Only non-progressing patients were then randomized after being stratified by carbohydrate antigen 19-9 (CA19-9) and SMAD4.

Participant milestones

Participant milestones
Measure	Chemotherapy + High Intensity Radiation Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent high intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy + Low Intensity Radiation Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent low intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy Gemcitabine and nab-paclitaxel until progression or unacceptable toxicity \[randomized to this arm after 3rd cycle and no progression\]
Overall Study STARTED	4	4	5
Overall Study COMPLETED	4	4	5
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

High or Standard Intensity Radiation Therapy After Gemcitabine Hydrochloride and Nab-paclitaxel in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemotherapy + High Intensity Radiation n=4 Participants Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent high intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy + Low Intensity Radiation n=4 Participants Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent low intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy n=5 Participants Gemcitabine and nab-paclitaxel until progression or unacceptable toxicity \[randomized to this arm after 3rd cycle and no progression\]	Total n=13 Participants Total of all reporting groups
Age, Continuous	63.5 years n=99 Participants	69 years n=107 Participants	66 years n=206 Participants	66 years n=7 Participants
Sex: Female, Male Female	4 Participants n=99 Participants	3 Participants n=107 Participants	2 Participants n=206 Participants	9 Participants n=7 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants	4 Participants n=7 Participants

PRIMARY outcome

Timeframe: From randomization until last follow-up. Analysis was to occur after a total of 140 deaths were reported within the pairing of each radiation arm with the chemotherapy alone arm. Maximum follow-up at time of study termination was 8.3 months.

Population: All randomized patients

Outcome measures

Outcome measures
Measure	Chemotherapy + High Intensity Radiation n=4 Participants Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent high intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy + Low Intensity Radiation n=4 Participants Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent low intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy n=5 Participants Gemcitabine and nab-paclitaxel until progression or unacceptable toxicity \[randomized to this arm after 3rd cycle and no progression\]
Overall Survival	4 Participants	4 Participants	5 Participants

SECONDARY outcome

Population: All randomized patients

Survival time is defined as time from randomization to date of death from any cause and was to be estimated by the Kaplan-Meier method. Given the limited follow-up due to early closure and termination of data collection, only the number of patients last reported to be alive at time of study termination is reported. Patients are categorized by SMAD4 status of "intact" (positive nuclear labeling is observed of the neoplastic cells ), "loss" (no labeling observed of the neoplastic cells) , or "undetermined" (insufficient material for immunostaining or results are equivocal). This study terminated early with only 20 registered (346 planned) and 13 randomized (288 planned). There are no proven results as to which category has better incomes, but this study hypothesizes that "intact" is highly correlated with local failures and "loss" is highly correlated with widespread metastasis, in which case "intact" would correspond with positive results relative to "loss".

Outcome measures

Outcome measures
Measure	Chemotherapy + High Intensity Radiation n=4 Participants Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent high intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy + Low Intensity Radiation n=4 Participants Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent low intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy n=5 Participants Gemcitabine and nab-paclitaxel until progression or unacceptable toxicity \[randomized to this arm after 3rd cycle and no progression\]
Overall Survival Within SMAD4 Subsets Intact	1 Participants	1 Participants	3 Participants
Overall Survival Within SMAD4 Subsets Loss	3 Participants	2 Participants	1 Participants
Overall Survival Within SMAD4 Subsets Undetermined	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From randomization until last follow-up. Maximum follow-up at time of study termination was 8.3 months.

Population: Randomized eligible patients with follow-up data.

Local progression is defined as least a 20% increase in the sum of diameters of the primary, taking as reference the baseline sum. Given the inherent inaccuracy in determining size of a primary pancreatic carcinoma, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm and progression must be demonstrated on at least two sequential scans. Metastatic failure is defined as metastatic disease. Local and distant failure were to be estimated by the cumulative incidence method. Given the limited follow-up due to early closure and termination of data collection, only the number of patients with failure is reported.

Outcome measures

Outcome measures
Measure	Chemotherapy + High Intensity Radiation n=1 Participants Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent high intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy + Low Intensity Radiation n=2 Participants Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent low intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy Gemcitabine and nab-paclitaxel until progression or unacceptable toxicity \[randomized to this arm after 3rd cycle and no progression\]
Patterns of Failure (Local and Metastatic Failure) Local Failure	0 Participants	0 Participants	—
Patterns of Failure (Local and Metastatic Failure) Metastatic Failure	0 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Baseline

Population: Because the study was terminated early, genetic SMAD4 status was not determined and therefore this analysis will not occur.

Outcome measures

Outcome data not reported

Adverse Events

Chemotherapy + High Intensity Radiation

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Chemotherapy + Low Intensity Radiation

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Chemotherapy

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Chemotherapy - Not Randomized

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Chemotherapy + High Intensity Radiation n=4 participants at risk Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent high intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy + Low Intensity Radiation n=4 participants at risk Induction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent low intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity	Chemotherapy n=5 participants at risk Gemcitabine and nab-paclitaxel until progression or unacceptable toxicity \[randomized to this arm after 3rd cycle and no progression\]	Chemotherapy - Not Randomized n=7 participants at risk Induction chemotherapy with three cycles of gemcitabine and nab-paclitaxel \[not randomized\]
Metabolism and nutrition disorders Hyponatremia	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	25.0% 1/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Cardiac disorders Atrial fibrillation	25.0% 1/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Diarrhea	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	25.0% 1/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	14.3% 1/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Vomiting	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	25.0% 1/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Edema limbs	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	25.0% 1/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Infections and infestations Lung infection	25.0% 1/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Neutrophil count decreased	25.0% 1/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	20.0% 1/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Platelet count decreased	25.0% 1/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations White blood cell decreased	25.0% 1/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Renal and urinary disorders Acute kidney injury	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/4 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	20.0% 1/5 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/7 Registered patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.

Other adverse events

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER