Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma
Conditions
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.
Interventions
Momelotinib (MMB) tablet(s) administered orally once or twice daily
DRUGCapecitabine
Capecitabine tablet(s) administered orally twice daily for 14 days, followed by 7 days off, until the end of treatment
DRUGOxaliplatin
Oxaliplatin administered intravenously over 120 minutes or as per institutional standard of care on Day 1 of each 21-day cycle.
Sponsors
Sierra Oncology LLC - a GSK company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) |
Countries
United States
Outcome results
None listed