A Study to Evaluate the Efficacy and Safety of Simtuzumab Combined With Gemcitabine for Metastatic Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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This study will compare the efficacy of simtuzumab (GS-6624) versus placebo in combination with gemcitabine in adults with pancreatic cancer. The treatment phase of this study will be comprised of 2 sequential parts: an open label treatment phase and a double-blinded treatment phase.

Official Title
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A Phase 2 Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-6624 Combined With Gemcitabine as First Line Treatment for Metastatic Pancreatic Adenocarcinoma

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Simtuzumab
* Drug: Gemcitabine
* Drug: Placebo to match simtuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Initial diagnosis of metastatic pancreatic cancer must have occurred ≤6 weeks prior to the completion of screening. The presence of measurable metastatic pancreatic cancer documented by contrast enhanced CT (or MRI) scan in addition to 1 of the following: Histological diagnosis of pancreatic adenocarcinoma confirmed by pathologist OR Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreatic origin in conjunction with either: The presence of a mass in the pancreas OR A history of resected pancreatic carcinoma Measurable disease per RECIST (ver. 1.1) ECOG Performance Status of 0 or 1. Adequate hepatic, hematologic and renal functions. Exclusion Criteria: A history or evidence of clinically significant disorder other than metastatic cancer of the pancreas. A diagnosis of pancreatic islet neoplasms. Subject has undergone major surgery other than diagnosis surgery within 4 weeks of randomization Presence of biliary obstruction requiring external drainage Brain metastases. Unstable cardiovascular function within the last 6 months of screening Clinically active liver disease, including active viral hepatitis (HBV or HCV) or cirrhosis Known HIV infection. Uncontrolled hypertension at Screening History or presence of any form of cancer, other than pancreatic cancer, within the 3 years prior to enrollment Prior or concurrent anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) for the treatment of inoperable locally advanced or metastatic pancreatic cancer; prior radiotherapy and chemotherapy given as pre-operative neoadjuvant therapy or radio sensitizers for locally advanced pancreatic cancer are allowed. Uncontrolled systemic fungal, bacterial or viral infection Participation in an investigational drug or device trial with therapeutic intent within 30 days prior to study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simtuzumab (open-label)<br>Participants will receive simtuzumab 700 mg plus gemcitabine in cycles of 28 days for up to 3 years. | Drug: Simtuzumab<br>* Simtuzumab administered intravenously every 2 weeks for a total of 2 infusions (Days 1 and 15)<br>* Other names: GS-6624;Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m^2 administered intravenously on Days 1, 8, and 15 of each 28-day cycle<br>* Other names: Gemzar®;|
| Experimental: Simtuzumab 200 mg (randomized)<br>Participants will receive simtuzumab 200 mg plus gemcitabine in cycles of 28 days for up to 3 years. | Drug: Simtuzumab<br>* Simtuzumab administered intravenously every 2 weeks for a total of 2 infusions (Days 1 and 15)<br>* Other names: GS-6624;Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m^2 administered intravenously on Days 1, 8, and 15 of each 28-day cycle<br>* Other names: Gemzar®;|
| Experimental: Simtuzumab 700 mg (randomized)<br>Participants will receive simtuzumab 700 mg plus gemcitabine in cycles of 28 days for up to 3 years. | Drug: Simtuzumab<br>* Simtuzumab administered intravenously every 2 weeks for a total of 2 infusions (Days 1 and 15)<br>* Other names: GS-6624;Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m^2 administered intravenously on Days 1, 8, and 15 of each 28-day cycle<br>* Other names: Gemzar®;|
| Placebo Comparator: Placebo (randomized)<br>Participants will receive placebo to match simtuzumab plus gemcitabine in cycles of 28 days for up to 3 years. | Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m^2 administered intravenously on Days 1, 8, and 15 of each 28-day cycle<br>* Other names: Gemzar®;Drug: Placebo to match simtuzumab<br>* Placebo to match simtuzumab administered intravenously every 2 weeks for a total of 2 infusions (Days 1 and 15)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression free survival is measured as time from date of randomization to the earliest event time of death regardless of cause or first indication of disease progression. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is measured as time from date of randomization to death regardless of cause. | Up to 3 years | 
| Objective response | Objective response is assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 as complete response, partial response, stable disease, or progressive disease. | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology, Monoclonal Antibody, GSI, Gilead, Gilead Sciences, Pancreatic Cancer, PC, Gemcitabine, Phase 2, Phase II, GS-6624