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

NCT02101021 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-370-12962014-004480-20
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

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.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Lead-In Phase: Overall Survival (OS)

  Baseline up to the Date of Death or Censoring, up to 3 years

• Lead-In Phase: Progression-Free Survival (PFS)

  Baseline up to the Date of Event or Censoring, up to 3 years

• Lead-In Phase: Overall Response Rate (ORR)

  Baseline up to the Last Tumor Assessment Date, up to 3 years

• Randomized Treatment Phase: Progression-Free Survival (PFS)

  Baseline up to the Date of Event or Censoring, up to 3 years

• Randomized Treatment Phase: Overall Response Rate

  Baseline up to the Last Tumor Assessment Date, up to 3 years

Study Arms (2)

Momelotinib

EXPERIMENTAL

Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.

Drug: Momelotinib; Drug: Nab-paclitaxel; Drug: Gemcitabine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo to match momelotinib; Drug: Nab-paclitaxel; Drug: Gemcitabine

Interventions

Momelotinib DRUG

Tablet (s) administered orally once or twice daily

Also known as: GS-0387, CYT387

Momelotinib

Placebo to match momelotinib DRUG

Placebo to match momelotinib tablets administered orally once or twice daily

Placebo

Nab-paclitaxel DRUG

Intravenously administered over approximately 30-40 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle

Momelotinib; Placebo

Gemcitabine DRUG

Intravenously administered over approximately 30 minutes or as per institutional standard of care on Days 1, 8, and 15 of each cycle

Momelotinib; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Sierra Oncology LLC - a GSK company: lead

Study Sites (4)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, 46506, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; 130-nm albumin-bound paclitaxel; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 1, 2014
• Study Start: June 2, 2014
• Primary Completion: April 10, 2017
• Study Completion: April 10, 2017
• Last Updated: June 29, 2023
• Results First Posted: May 9, 2018

Record last verified: 2023-06

Locations

US (4)