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

Sierra Oncology

Status and phase: Terminated; Phase 3

Conditions: Metastatic Pancreatic Ductal Adenocarcinoma

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02101021

2014-004480-20 (EudraCT Number)

GS-US-370-1296

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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25 participants in 2 patient groups, including a placebo group

Momelotinib

Experimental group

Description:

Participants will receive momelotinib plus nab-paclitaxel and gemcitabine.

Treatment:

Drug: Gemcitabine

Drug: Momelotinib

Drug: Nab-paclitaxel

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Gemcitabine

Drug: Placebo to match momelotinib

Drug: Nab-paclitaxel