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

Primary Purpose

Metastatic Pancreatic Ductal Adenocarcinoma

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Momelotinib
Placebo to match momelotinib
Nab-paclitaxel
Gemcitabine
Sponsored by
Sierra Oncology LLC - a GSK company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Pancreatic Ductal Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cedars-Sinai Medical Center
  • Indiana University Health Goshen Center for Cancer Care
  • Dana Farber Cancer Institute
  • Northwest Medical Specialties, PLLC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Momelotinib

Placebo

Arm Description

Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.

Participants will receive placebo to match momelotinib plus nab-paclitaxel and gemcitabine.

Outcomes

Primary Outcome Measures

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.
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

Secondary Outcome Measures

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
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.
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.
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
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)

Full Information

First Posted
March 28, 2014
Last Updated
June 14, 2023
Sponsor
Sierra Oncology LLC - a GSK company
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1. Study Identification

Unique Protocol Identification Number
NCT02101021
Brief Title
Gemcitabine and Nab-paclitaxel Combined With Momelotinib in Participants With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Study Start Date
June 2, 2014 (Actual)
Primary Completion Date
April 10, 2017 (Actual)
Study Completion Date
April 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sierra Oncology LLC - a GSK company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Ductal Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Momelotinib
Arm Type
Experimental
Arm Description
Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo to match momelotinib plus nab-paclitaxel and gemcitabine.
Intervention Type
Drug
Intervention Name(s)
Momelotinib
Other Intervention Name(s)
GS-0387, CYT387
Intervention Description
Tablet (s) administered orally once or twice daily
Intervention Type
Drug
Intervention Name(s)
Placebo to match momelotinib
Intervention Description
Placebo to match momelotinib tablets administered orally once or twice daily
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Intervention Description
Intravenously administered over approximately 30-40 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Intravenously administered over approximately 30 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle
Primary Outcome Measure Information:
Title
Lead-In Phase: Percentage of Participants Experiencing Treatment-Emergent Dose Limiting Toxicity (DLT) Adverse Events
Description
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.
Time Frame
Up to 28 Days
Title
Randomized Treatment Phase: Overall Survival (OS)
Description
Overall survival was defined as the time interval from first dose date of MMB to death from any cause
Time Frame
Baseline up to the Date of Death or Censoring, up to 3 years
Secondary Outcome Measure Information:
Title
Lead-In Phase: Overall Survival (OS)
Description
Overall survival was defined as the time interval from first dose date of MMB to death from any cause
Time Frame
Baseline up to the Date of Death or Censoring, up to 3 years
Title
Lead-In Phase: Progression-Free Survival (PFS)
Description
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.
Time Frame
Baseline up to the Date of Event or Censoring, up to 3 years
Title
Lead-In Phase: Overall Response Rate (ORR)
Description
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.
Time Frame
Baseline up to the Last Tumor Assessment Date, up to 3 years
Title
Randomized Treatment Phase: Progression-Free Survival (PFS)
Description
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
Time Frame
Baseline up to the Date of Event or Censoring, up to 3 years
Title
Randomized Treatment Phase: Overall Response Rate
Description
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)
Time Frame
Baseline up to the Last Tumor Assessment Date, up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Indiana University Health Goshen Center for Cancer Care
City
Goshen
State/Province
Indiana
ZIP/Postal Code
46506
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Northwest Medical Specialties, PLLC
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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