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

• ClinicalTrials.gov Identifier: NCT02101021
• Recruitment Status: Terminated
• First Posted: April 1, 2014
• Results First Posted: May 9, 2018
• Last Update Posted: February 18, 2019
• Sponsor: Sierra Oncology, Inc.
• Information provided by (Responsible Party): Sierra Oncology, Inc.

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Pancreatic Ductal Adenocarcinoma	Drug: Momelotinib; Drug: Placebo to match momelotinib; Drug: Nab-paclitaxel; Drug: Gemcitabine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 2, 2014
• Actual Primary Completion Date: April 10, 2017
• Actual Study Completion Date: April 10, 2017

Arms and Interventions

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: Placebo to match momelotinib; Placebo to match momelotinib tablets administered orally once or twice daily; 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

Outcome Measures

Primary Outcome Measures :

1. Lead-In Phase: Percentage of Participants Experiencing Treatment-Emergent Dose Limiting Toxicity (DLT) Adverse Events [ Time Frame: Up to 28 Days ]

   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.

2. Randomized Treatment Phase: Overall Survival (OS) [ Time Frame: Baseline up to the Date of Death or Censoring, up to 3 years ]
   Overall survival was defined as the time interval from first dose date of MMB to death from any cause

Secondary Outcome Measures :

1. Lead-In Phase: Overall Survival (OS) [ Time Frame: Baseline up to the Date of Death or Censoring, up to 3 years ]
   Overall survival was defined as the time interval from first dose date of MMB to death from any cause
2. Lead-In Phase: Progression-Free Survival (PFS) [ Time Frame: Baseline up to the Date of Event or Censoring, up to 3 years ]
   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.
3. Lead-In Phase: Overall Response Rate (ORR) [ Time Frame: Baseline up to the Last Tumor Assessment Date, up to 3 years ]
   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.
4. Randomized Treatment Phase: Progression-Free Survival (PFS) [ Time Frame: Baseline up to the Date of Event or Censoring, up to 3 years ]
   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
5. Randomized Treatment Phase: Overall Response Rate [ Time Frame: Baseline up to the Last Tumor Assessment Date, up to 3 years ]
   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)

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, California

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

United States, Indiana

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, United States, 46506

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Washington

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States, 98405

Sponsors and Collaborators

Sierra Oncology, Inc.

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

  Study Documents (Full-Text)

Documents provided by Sierra Oncology, Inc.:

Study Protocol: Original  [PDF] February 11, 2014

Study Protocol: Amendment 1  [PDF] March 14, 2014

Study Protocol: Amendment 2  [PDF] August 25, 2014

Study Protocol: Amendment 3  [PDF] July 16, 2015

Statistical Analysis Plan  [PDF] July 10, 2017

More Information

• Responsible Party: Sierra Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02101021
• Other Study ID Numbers: GS-US-370-1296; 2014-004480-20 ( EudraCT Number )
• First Posted: April 1, 2014
• Results First Posted: May 9, 2018
• Last Update Posted: February 18, 2019
• Last Verified: January 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gemcitabine; Paclitaxel; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Protein Kinase Inhibitors