NCT02309177

Safety Study of Nivolumab With Nab-Paclitaxel Plus or Minus Gemcitabine in Pancreatic Cancer, Nab-Paclitaxel / Carboplatin in Stage IIIB/IV Non-Small Cell Lung Cancer or Nab-Paclitaxel in Recurrent Metastatic Breast Cancer

A Phase 1, Open-label, Multicenter, Safety Study of Nivolumab (Bms-936558) in Combination With Nab-pacitaxel Plus or Minus Gemcitabine in Pancreatic Cancer, Nab-paclitaxel/Carboplatin in Stage Iiib/iv Non-small Cell Lung Cancer or Nab-paclitaxel in Metastastic Breast Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 114 (actual)
• Sponsor: Celgene · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess safety of nab-paclitaxel based chemotherapy regimens administered prior to and/or in combination with nivolumab in Pancreatic Cancer, Non Small Cell Lung Cancer (NSCLC) and Metastatic Breast Cancer (mBC).

Detailed description

This will be a phase 1, open-label, multicenter, safety study of nab-paclitaxel based chemotherapy regimens administered prior to and/or in combination with nivolumab in Pancreatic Cancer, NSCLC and mBC. This is a six arm study assessing two treatment arms per tumor-type/indication: * Adenocarcinoma of the pancreas with 1 prior systemic chemotherapy (Arm A, Part 1 only); and subsequently no prior chemotherapy, surgery or radiation therapy for locally advanced or metastatic disease (Arm A, Part 2 and Arm B): * Panc Ca Arm A: nab-paclitaxel with nivolumab starting at Cycle 1. * Panc Ca Arm B: nab-paclitaxel/gemcitabine with nivolumab starting at Cycle 1. * Stage IIIB or IV NSCLC with no prior chemotherapy for metastatic disease and who are not candidates for curative surgery or radiation: * NSCLC Arm C: nab-paclitaxel/carboplatin x 4 cycles with nivolumab starting Cycle 1 and continuing as monotherapy starting at Cycle 5. * NSCLC Arm D: nab-paclitaxel/carboplatin x 4 cycles with nivolumab starting Cycle 3 and continuing as monotherapy starting at Cycle 5 * HER2-negative recurrent metastatic breast cancer after one prior regimen for mBC, including an anthracycline unless clinically contraindicated: * mBC Arm E: weekly nab-paclitaxel with nivolumab starting at Cycle 3. * mBC Arm F: q3weekly nab-paclitaxel with nivolumab starting at Cycle 3. Enrollment in each treatment arm will be conducted in two sequential parts to allow for the evaluation of the DLT in Part 1 prior to expanding the treatment arm in Part 2. Part 1: Part 1 will assess the Dose Limiting Toxicity (DLT) of the nivolumab dose in combination with nab-paclitaxel regimens in each treatment arm. Subjects who meet the entry criteria will be assigned to the respective treatment arm based on tumor type and indication as outlined above. Panc Ca Arms A and B, as well as NSCLC Arms C and D, will enroll sequentially in Part 1. The safety of nivolumab in combination with nabpaclitaxel, without gemcitabine, will first be assessed in Arm A in subjects with one prior systemic chemotherapy regimen for locally advanced or metastatic disease. Panc Ca Arm B may begin enrolling subjects in Part 1, if Panc Ca Arm A is deemed safe, based on DLT criteria. Similarly, NSCLC Arm D will begin to enroll in Part 1 after NSCLC Arm C is deemed safe to expand in Part 2. However, Arm D may be initiated, even if Arm C is not to proceed for Part 2, if the totality of data from Arm C and emerging data from this and other studies in NSCLC with nivolumab in combination with platinum chemotherapy doublets support the decision. Unlike the Panc Ca and NSCLC arms, the two mBC arms (Arms E and F) will be initiated simultaneously. Subjects will be assigned randomly between treatment arms of a tumor type/indication whenever both treatment arms are enrolling. An IRT system will be used to ensure the central random allocation of subjects. Part 2: Treatment arms deemed safe within each tumor-type/indication may be expanded using the RP2D with an additional approximately 14 subjects (to attain a total of 20 nivolumab-treated subjects) to further assess safety and tolerability, as well as explore anti-tumor activity of the proposed regimens. Since the primary population for the pancreas arms is in subjects with no prior chemotherapy, surgery or radiation therapy, enrollment in Part 2 for Panc Ca Arm A will continue until 20 such subjects have been treated with at least one dose of nivolumab. Additionally, in Parts 1 and 2 overall, each mBC Arm (E and F) will enroll a minimum of 9 subjects with triple- negative breast cancer (TNBC), treated at the RP2D. For both Part 1 and 2, subjects may continue to receive their assigned treatment regimen until Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined progression or until unacceptable toxicity. However, the chemotherapy doublet will only be given for 4 cycles in the NSCLC arms; thereafter, nivolumab will be given as monotherapy.

Conditions

• Breast Neoplasms
• Pancreatic Neoplasms

Interventions

Type	Name	Description
DRUG	nab-Paclitaxel
DRUG	Nivolumab
DRUG	Gemcitabine
DRUG	Carboplatin

Timeline

• Start date: 2015-01-12
• Primary completion: 2018-09-12
• Completion: 2018-09-12
• First posted: 2014-12-05
• Last updated: 2019-05-31

Locations

15 sites across 1 country: United States