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

• ClinicalTrials.gov Identifier: NCT02244489
• Recruitment Status: Terminated
• First Posted: September 19, 2014
• Last Update Posted: February 1, 2019
• Sponsor: Sierra Oncology, Inc.
• Information provided by (Responsible Party): Sierra Oncology, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma	Drug: Momelotinib (MMB); Drug: Capecitabine; Drug: Oxaliplatin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Study Evaluating Momelotinib Combined With Capecitabine and Oxaliplatin in Subjects With Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma
• Actual Study Start Date: November 5, 2014
• Actual Primary Completion Date: March 8, 2017
• Actual Study Completion Date: April 5, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Momelotinib (MMB)+capecitabine; Participants will receive momelotinib (MMB)+capecitabine at varying dose levels to determine the MTD for momelotinib (MMB) and capecitabine.	Drug: Momelotinib (MMB); Momelotinib (MMB) tablet(s) administered orally once or twice daily; Other Names: GS-0387; CYT387; Drug: Capecitabine; Capecitabine tablet(s) administered orally twice daily for 14 days, followed by 7 days off, until the end of treatment
Experimental: Momelotinib (MMB)+capecitabine+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.	Drug: Momelotinib (MMB); Momelotinib (MMB) tablet(s) administered orally once or twice daily; Other Names: GS-0387; CYT387; Drug: Capecitabine; Capecitabine tablet(s) administered orally twice daily for 14 days, followed by 7 days off, until the end of treatment; Drug: Oxaliplatin; Oxaliplatin administered intravenously over 120 minutes or as per institutional standard of care on Day 1 of each 21-day cycle.

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose limiting toxicities [ Time Frame: 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.
2. Incidence of adverse events, assessment of clinical laboratory test findings, physical examination, 12-lead electrocardiogram (ECG), and vital signs measurements [ Time Frame: Up to 2 years ]
   This composite endpoint will measure the safety profile of momelotinib.

Secondary Outcome Measures :

1. Overall response rate [ Time Frame: 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.
2. Overall survival [ Time Frame: Up to 2 years ]
   Overall survival (OS) is defined as the interval from first dose date of study drug to death from any cause.
3. Progression-free survival [ Time Frame: 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.
4. Pharmacokinetic (PK) profile of momelotinib (MMB) [ Time Frame: 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)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key 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 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.

Contacts and Locations

Locations

United States, Arizona

Scottsdale Healthcare Research Institute

Scottsdale, Arizona, United States, 85258

United States, California

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

United States, Tennessee

Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Virginia

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States, 22031

Sponsors and Collaborators

Sierra Oncology, Inc.

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

More Information

• Responsible Party: Sierra Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02244489 History of Changes
• Other Study ID Numbers: GS-US-370-1369
• First Posted: September 19, 2014
• Last Update Posted: February 1, 2019
• Last Verified: January 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Capecitabine; Oxaliplatin; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors