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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02101021
First received: March 28, 2014
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

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 combined with nab-paclitaxel and gemcitabine in adults with previously untreated metastatic pancreatic ductal adenocarcinoma. The randomized treatment phase will evaluate the efficacy, safety, and tolerability of nab-paclitaxel and gemcitabine combined with either momelotinib administered at the MTD or placebo in adults with previously untreated metastatic pancreatic ductal adenocarcinoma as measured by improvement in overall survival (OS), progression free survival (PFS), and overall response rate (ORR). 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 5 years.


Condition Intervention Phase
Metastatic Pancreatic Ductal Adenocarcinoma
Drug: Momelotinib
Drug: Placebo to match momelotinib
Drug: Nab-paclitaxel
Drug: Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-blind 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • For the lead-in phase, the incidence of DLTs [ Time Frame: Up to Day 28 ] [ Designated as safety issue: No ]
    Dose limiting toxicities (DLTs) refer to toxicities experienced during the first 28 days of treatment that have been judged to be clinically significant and related to study treatment.

  • For the randomized treatment phase, overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the interval from randomization to death from any cause.


Secondary Outcome Measures:
  • For the lead-in phase, overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the interval from the first dose date of drug to death from any cause.

  • For the lead-in phase, progression free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Progression free survival is defined as the interval from the first dose date of drug during the lead-in phase 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.

  • For the lead-in phase, overall response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Overall response rate is defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR) as assessed by RECIST v1.1.

  • For the randomized treatment phase, progression free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Progression free survival is defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is progression based on RECIST v1.1 criteria.

  • For the randomized treatment phase, overall response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Overall response rate is defined as the proportion of subjects who achieve a CR or PR as assessed by RECIST v1.1.


Estimated Enrollment: 336
Study Start Date: June 2014
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Momelotinib
Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.
Drug: Momelotinib
Momelotinib tablets administered orally once or twice daily
Other Names:
  • GS-0387
  • CYT387
Drug: Nab-paclitaxel
Nab-paclitaxel administered intravenously over approximately 30-40 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle
Drug: Gemcitabine
Gemcitabine administered intravenously 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
Nab-paclitaxel administered intravenously over approximately 30-40 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle
Drug: Gemcitabine
Gemcitabine administered intravenously over approximately 30 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Initial diagnosis of metastatic pancreatic adenocarcinoma must have occurred ≤ 6 wks prior to enrollment
  • 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 < 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)

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02101021

Contacts
Contact: Clinical Study Team momelotinib.studies@gilead.com

Locations
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
United States, Indiana
Indiana University Health Goshen Center for Cancer Care Recruiting
Goshen, Indiana, United States, 46526
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, Washington
Northwest Medical Specialties Recruiting
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Peter Lee, MD, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02101021     History of Changes
Other Study ID Numbers: GS-US-370-1296
Study First Received: March 28, 2014
Last Updated: September 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma, Ductal, Breast
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Ductal
Neoplasms, Ductal, Lobular, and Medullary
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Paclitaxel
Gemcitabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on September 22, 2014