Pembrolizumab-based Therapy in Previously Treated High Grade Neuroendocrine Carcinomas
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|ClinicalTrials.gov Identifier: NCT03136055|
Recruitment Status : Active, not recruiting
First Posted : May 2, 2017
Last Update Posted : October 9, 2020
|Condition or disease||Intervention/treatment||Phase|
|High Grade Malignant Neuroendocrine Carcinoma (Diagnosis)||Drug: Pembrolizumab Drug: Irinotecan Drug: Paclitaxel||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||There are two parts of the study. In Part A, subjects are treated with pembrolizumab alone, and in Part B with pembrolizumab plus chemotherapy (physician's choice, paclitaxel or irinotecan). Adaptive Simon's two-stage design is used. The overall plan hinges on the activity of single agent pembrolizumab in the first stage of Part A. If there is sufficient activity in the first stage of Part A, the study will expand to the second stage of Part A and forgo Part B. If there is insufficient activity in the first stage of Part A, the study will proceed to the first stage of Part B (pembrolizumab plus chemotherapy).|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Pembrolizumab-based Therapy in Previously Treated High Grade Neuroendocrine Carcinomas|
|Actual Study Start Date :||August 10, 2017|
|Estimated Primary Completion Date :||October 1, 2022|
|Estimated Study Completion Date :||July 1, 2023|
Experimental: High-Grade Extrapulmonary NEC
Part A: 200 mg of pembrolizumab will be given every three weeks via IV infusion.
Part B: 200 mg of pembrolizumab will be given every three weeks via IV infusion and, either
200 mg every 3 weeks via IV infusion.
Other Name: Keytruda
For patients in part B receiving pembrolizumab and chemotherapy with irinotecan. The starting dose for the safety lead-in is 125 mg/m2 irinotecan via IV infusion in a 2 weeks on, 1 week off format over 3 week cycles.
If the initial dose is not tolerated, the dose level will be decreased to 100 mg/m2.
Other Name: Camptosar
For patients in part B receiving pembrolizumab and chemotherapy with paclitaxel. Patients will receive 80 mg/m2 of paclitaxel via IV infusion every week, with treatment breaks as needed.
Other Name: Taxol
- Overall Response Rate (ORR) [ Time Frame: Approximately 2 years ]ORR is defined as the proportion of the subjects in the analysis population who demonstrated complete response (CR) or partial response (PR) radiographically according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by investigator. The analysis will include all subjects treated (ITT) who received at least one dose of the study treatment. If the final study consists of both Part A and Part B, the analysis will be done separately for each part.
- Overall Survival (OS) [ Time Frame: Over the duration of the study, which is estimated to be approximately 32 months. ]Overall survival is defined as the time from the first day of study treatment with protocol therapy to the date of death due to any cause. Kaplan-Meier method will be used to summarize OS. Median OS and its 95% confidence interval will be obtained for Part A and B (if available) separately.
- Duration of Response (DOR) [ Time Frame: Over the duration of the study, which is estimated to be approximately 32 months. ]Duration of Response is defined as the time from the date of first response (CR or PR) until the date of disease progression or death. Kaplan-Meier method will be used to summarize DOR. Median DOR and its 95% confidence interval will be obtained for Part A and B (if available) separately. Only patients who have a demonstrated response will be used in final analysis.
- Progression free survival (PFS) [ Time Frame: Over the duration of the study, which is estimated to be approximately 32 months. ]Progression free survival is defined as the time from the first day of study treatment with protocol therapy to the date of documented tumor progression or death due to any cause, whichever occurs first, as determined by The immune-related response criteria (irRC) for the immune-related progression-free survival (irPFS) and RECIST v1.1 for PFS. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment. Kaplan-Meier method will be used to summarize progression free survival; median irPFS and PFS will be estimated with 95% confidence interval for Part A and B (if available) separately.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03136055
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94115|
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Emily Bergsland, MD||University of California, San Francisco|