Clinical trial NCT02101021: Gemcitabine and Nab-paclitaxel Combined With Momelotinib in Participants With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
Lead sponsor: Sierra Oncology LLC - a GSK company
Sponsor class: INDUSTRY
First posted: 2014-04-01
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Lead-In Phase: Percentage of Participants Experiencing Treatment-Emergent Dose Limiting Toxicity (DLT) Adverse Events
timeFrame: Up to 28 Days
measure: Randomized Treatment Phase: Overall Survival (OS)
timeFrame: Baseline up to the Date of Death or Censoring, up to 3 years
Secondary outcomes:
measure: Lead-In Phase: Overall Survival (OS)
timeFrame: Baseline up to the Date of Death or Censoring, up to 3 years
measure: Lead-In Phase: Progression-Free Survival (PFS)
timeFrame: Baseline up to the Date of Event or Censoring, up to 3 years
measure: Lead-In Phase: Overall Response Rate (ORR)
timeFrame: Baseline up to the Last Tumor Assessment Date, up to 3 years
measure: Randomized Treatment Phase: Progression-Free Survival (PFS)
timeFrame: Baseline up to the Date of Event or Censoring, up to 3 years
measure: Randomized Treatment Phase: Overall Response Rate
timeFrame: Baseline up to the Last Tumor Assessment Date, up to 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Goshen
country: United States
facility: Indiana University Health Goshen Center for Cancer Care
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: