Momelotinib Combined With Capecitabine and Oxaliplatin in Adults With Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma

Phase 1

Terminated

• Conditions: Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma
• Interventions: Drug: Momelotinib (MMB); Drug: Capecitabine; Drug: Oxaliplatin

• Registration Number: NCT02244489
• Lead Sponsor: Sierra Oncology LLC - a GSK company

Brief Summary

This study will evaluate the safety, tolerability, and define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with capecitabine and oxaliplatin in adults with relapsed/refractory metastatic pancreatic ductal adenocarcinoma.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-09-17
• Study First Submitted QC: 2014-09-17
• Study First Posted: 2014-09-19
• Study Start: 2014-11-05
• Primary Completion: 2017-03-08
• Study Completion: 2017-04-05
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-30
• Last Update Posted: 2019-02-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Relapsed or refractory metastatic pancreatic adenocarcinoma

• Received 1 prior chemotherapy regimen for metastatic pancreatic ductal adenocarcinoma (not including neoadjuvant and/or adjuvant therapy)

• Measurable disease per RECIST v1.1

• Adequate organ function defined as

  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN) OR ≤ 5 x ULN if liver metastases are present; total conjugated bilirubin ≤ 2 x ULN
  • Absolute neutrophil count (ANC) ≥1500 cells/mm^3, platelet ≥100,000 cells/mm^3, hemoglobin ≥ 9.0 g/dL
  • Creatinine clearance (CrCl) > 50 ml/min as calculated by the Cockroft-Gault method

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Key

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Exclusion Criteria

• Received more than 1 prior line of chemotherapy for metastatic pancreatic ductal adenocarcinoma
• Major surgery within 21 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)
• Chemotherapy, immunotherapy, biologics, and/or investigational therapy within 21 days prior to first dose of study drug
• Known positive status for HIV, chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier
• Known dihydropyrimidine dehydrogenase deficiency
• Peripheral neuropathy ≥ Grade 2
• Any condition that impairs gastrointestinal absorption of drug
• 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
• 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Momelotinib (MMB)+capecitabine	Momelotinib (MMB)	Participants will receive momelotinib (MMB)+capecitabine at varying dose levels to determine the MTD for momelotinib (MMB) and capecitabine.
Momelotinib (MMB)+capecitabine+oxaliplatin	Momelotinib (MMB)	Upon reaching the MTD for momelotinib (MMB) and capecitabine or if no MTD is reached, participants will receive momelotinib (MMB)+capecitabine at the MTD plus oxaliplatin at varying dose levels to determine the MTD of combination capecitabine, momelotinib (MMB), and oxaliplatin.
Momelotinib (MMB)+capecitabine+oxaliplatin	Capecitabine	Upon reaching the MTD for momelotinib (MMB) and capecitabine or if no MTD is reached, participants will receive momelotinib (MMB)+capecitabine at the MTD plus oxaliplatin at varying dose levels to determine the MTD of combination capecitabine, momelotinib (MMB), and oxaliplatin.
Momelotinib (MMB)+capecitabine	Capecitabine	Participants will receive momelotinib (MMB)+capecitabine at varying dose levels to determine the MTD for momelotinib (MMB) and capecitabine.
Momelotinib (MMB)+capecitabine+oxaliplatin	Oxaliplatin	Upon reaching the MTD for momelotinib (MMB) and capecitabine or if no MTD is reached, participants will receive momelotinib (MMB)+capecitabine at the MTD plus oxaliplatin at varying dose levels to determine the MTD of combination capecitabine, momelotinib (MMB), and oxaliplatin.

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities	Up to 21 days	Dose limiting toxicities refer to toxicities experienced during the first 21 days of treatment that have been judged to be clinically significant and at least possibly related to study treatment.
Incidence of adverse events, assessment of clinical laboratory test findings, physical examination, 12-lead electrocardiogram (ECG), and vital signs measurements	Up to 2 years	This composite endpoint will measure the safety profile of momelotinib.

Secondary Outcome Measures

Name	Time	Method
Progression-free survival	Up to 2 years	Progression-free survival (PFS) is defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is progression based on RECIST criteria v1.1.
Pharmacokinetic (PK) profile of momelotinib (MMB)	Predose and postdose on Day 15	This composite endpoint will measure the plasma PK profile of momelotinib (MMB). The following parameters will be measured, where applicable: * Cmax: maximum observed concentration of drug in plasma; * Ctau: observed drug concentration at the end of the dosing interval; * AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
Overall response rate	Up to 2 years	Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Overall survival	Up to 2 years	Overall survival (OS) is defined as the interval from first dose date of study drug to death from any cause.

Trial Locations

Locations (4)

Scottsdale Healthcare Research Institute; 🇺🇸 Scottsdale, Arizona, United States

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

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Virginia Cancer Specialists, PC; 🇺🇸 Fairfax, Virginia, United States