Gemcitabine and Nab-paclitaxel Combined With Momelotinib in Participants With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma

A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Gemcitabine and Nab-paclitaxel Combined With Momelotinib in Subjects With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma Preceded by a Dose-finding, Lead-in Phase

There will be two phases to this study. The lead-in phase will evaluate the safety, pharmacokinetics, and define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with nab-paclitaxel and gemcitabine (nab-P + G) in adults with previously untreated metastatic pancreatic ductal adenocarcinoma. The randomized treatment phase will evaluate the efficacy, safety, and tolerability of nab-P + G with either MMB administered at the MTD or placebo in adults with previously untreated metastatic pancreatic ductal adenocarcinoma. Participants will continue study treatment until disease progression, unacceptable toxicity, consent withdrawal, or participant's refusal of treatment. Following treatment, participants will be followed for safety for 30 days and for survival approximately every 3 months for up to 3 years.

Study Overview

• Status: Terminated
• Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Momelotinib; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Placebo to match momelotinib

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Indiana
    • Goshen, Indiana, United States, 46506
      • Indiana University Health Goshen Center for Cancer Care
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Presence of metastatic pancreatic adenocarcinoma plus 1 of the following:

  • Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically, OR

  • Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreas origin in conjunction with either:

    • The presence of a mass in the pancreas, OR
    • A history of resected pancreatic adenocarcinoma
• Measurable disease per RECIST v1.1

• Adequate organ function defined as follows:

  • Total bilirubin ≤ 1.25 x upper limit of the normal range (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
  • Absolute neutrophil count (ANC) > 1500 cells/mm^3, platelet > 100,000 cells/mm^3, hemoglobin > 9 g/dL
  • Serum creatinine < ULN OR calculated creatinine clearance (CrCl) of ≥ 60 ml/min
• Eastern Cooperative Oncology Group (ECOG ) 0 or 1
• Modified Glasgow prognostic score (mGPS) of 1 or 2 at Screening (randomized phase only)

Key Exclusion Criteria:

• Neoadjuvant or adjuvant chemotherapy or chemoradiotherapy for pancreatic adenocarcinoma
• Currently or previously treated with biologic, small molecule, immunotherapy, chemotherapy, or other agents for metastatic pancreatic carcinoma
• Major surgery within 28 days of first dose of study drug
• Minor surgical procedure(s) within 7 days of enrollment or not yet recovered from prior minor surgery (placement of central venous access device, fine needle aspiration, or endoscopic biliary stent ≥ 1 day before enrollment is acceptable)
• Known positive status for HIV
• Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier
• Peripheral neuropathy ≥ Grade 2
• Known or suspected brain or central nervous system metastases
• Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma, adenocarcinoma originating from the biliary tree or cystadenocarcinoma
• History of interstitial pneumonitis and/or require supplemental oxygen therapy
• External biliary drain
• Documented myocardial infarction or unstable/uncontrolled cardiac disease within 6 months of enrollment

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Momelotinib; Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.	Drug: Momelotinib; Tablet (s) administered orally once or twice daily; Other Names: GS-0387; CYT387; Drug: Nab-paclitaxel; Intravenously administered over approximately 30-40 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle; Drug: Gemcitabine; Intravenously administered over approximately 30 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle
Placebo Comparator: Placebo; Participants will receive placebo to match momelotinib plus nab-paclitaxel and gemcitabine.	Drug: Nab-paclitaxel; Intravenously administered over approximately 30-40 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle; Drug: Gemcitabine; Intravenously administered over approximately 30 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle; Drug: Placebo to match momelotinib; Placebo to match momelotinib tablets administered orally once or twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lead-In Phase: Percentage of Participants Experiencing Treatment-Emergent Dose Limiting Toxicity (DLT) Adverse Events	Dose limiting toxicities were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Dose limiting toxicities referred to toxicities experienced during the first 28 days (Cycle 1) of treatment that were judged to be clinically significant and related to study treatment. No statistical analysis was planned or performed for this endpoint.	Up to 28 Days
Randomized Treatment Phase: Overall Survival (OS)	Overall survival was defined as the time interval from first dose date of MMB to death from any cause	Baseline up to the Date of Death or Censoring, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lead-In Phase: Overall Survival (OS)	Overall survival was defined as the time interval from first dose date of MMB to death from any cause	Baseline up to the Date of Death or Censoring, up to 3 years
Lead-In Phase: Progression-Free Survival (PFS)	Progression-free survival was defined as the time interval from the first dose of MMB to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression is progression based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria v1.1. Data from survival, non-progressing participants will be censored at the earliest of the time of initiation of anti-tumor therapy other than the study treatment or the last time that lack of definitive disease progression was objectively documented while on study.	Baseline up to the Date of Event or Censoring, up to 3 years
Lead-In Phase: Overall Response Rate (ORR)	The ORR was defined as the proportion of participants who achieved a best overall response (BOR) during MMB therapy of complete response (CR) or partial response (PR) as assessed by RECIST v1.1.	Baseline up to the Last Tumor Assessment Date, up to 3 years
Randomized Treatment Phase: Progression-Free Survival (PFS)	Progression-free survival was defined as the time interval from the first dose of MMB to the earlier of the first documentation of definitive disease progression or death from any cause	Baseline up to the Date of Event or Censoring, up to 3 years
Randomized Treatment Phase: Overall Response Rate	The ORR was defined as the proportion of subjects who achieved a best overall response (BOR) during MMB therapy of complete response (CR) or partial response (PR)	Baseline up to the Last Tumor Assessment Date, up to 3 years

Collaborators and Investigators

• Sponsor: Sierra Oncology LLC - a GSK company
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2014
• Primary Completion (Actual): April 10, 2017
• Study Completion (Actual): April 10, 2017

Study Registration Dates

• First Submitted: March 28, 2014
• First Submitted That Met QC Criteria: March 28, 2014
• First Posted (Estimated): April 1, 2014

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; Gemcitabine
• Other Study ID Numbers: GS-US-370-1296; 2014-004480-20 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No