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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1b Study Evaluating Momelotinib Combined With Capecitabine and Oxaliplatin in Subjects With Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma

Conditions
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Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: Momelotinib (MMB)
* Drug: Capecitabine
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities | 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. | Up to 21 days | 
| Incidence of adverse events, assessment of clinical laboratory test findings, physical examination, 12-lead electrocardiogram (ECG), and vital signs measurements | This composite endpoint will measure the safety profile of momelotinib. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | 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. | Up to 2 years | 
| Overall survival | Overall survival (OS) is defined as the interval from first dose date of study drug to death from any cause. | Up to 2 years | 
| Progression-free survival | 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. | Up to 2 years | 
| Pharmacokinetic (PK) profile of momelotinib (MMB) | 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) | Predose and postdose on Day 15 |