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

Phase 3

Terminated

• Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
• Interventions: Drug: Placebo to match momelotinib; Drug: Momelotinib; Drug: Nab-paclitaxel; Drug: Gemcitabine

• Registration Number: NCT02101021
• Lead Sponsor: Sierra Oncology LLC - a GSK company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-03-28
• Study First Submitted QC: 2014-03-28
• Study First Posted: 2014-04-01
• Study Start: 2014-06-02
• Primary Completion: 2017-04-10
• Study Completion: 2017-04-10
• Results First Submitted: 2018-04-06
• Results First Submitted QC: 2018-04-06
• Results First Posted: 2018-05-09
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-14
• Last Update Posted: 2023-06-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 25

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Momelotinib	Nab-paclitaxel	Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.
Placebo	Placebo to match momelotinib	Participants will receive placebo to match momelotinib plus nab-paclitaxel and gemcitabine.
Placebo	Nab-paclitaxel	Participants will receive placebo to match momelotinib plus nab-paclitaxel and gemcitabine.
Momelotinib	Gemcitabine	Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.
Momelotinib	Momelotinib	Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.
Placebo	Gemcitabine	Participants will receive placebo to match momelotinib plus nab-paclitaxel and gemcitabine.

Primary Outcome Measures

Name	Time	Method
Lead-In Phase: Percentage of Participants Experiencing Treatment-Emergent Dose Limiting Toxicity (DLT) Adverse Events	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.
Randomized Treatment Phase: Overall Survival (OS)	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

Name	Time	Method
Lead-In Phase: Progression-Free Survival (PFS)	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.
Lead-In Phase: Overall Survival (OS)	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
Lead-In Phase: Overall Response Rate (ORR)	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.
Randomized Treatment Phase: Progression-Free Survival (PFS)	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
Randomized Treatment Phase: Overall Response Rate	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)

Trial Locations

Locations (4)

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Indiana University Health Goshen Center for Cancer Care; 🇺🇸 Goshen, Indiana, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Northwest Medical Specialties, PLLC; 🇺🇸 Tacoma, Washington, United States