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

Phase 3TerminatedNCT02101021

Sierra Oncology LLC - a GSK company25 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 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

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

Secondary Outcomes

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

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

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.

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

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.

Time frame: Baseline up to the Last Tumor Assessment Date, up to 3 years

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