Study of Ruxolitinib in Pancreatic Cancer Patients

Study Overview
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Brief Summary
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The purpose of this study was to determine whether ruxolitinib added to capecitabine is effective in improving the overall survival of patients with metastatic pancreatic cancer.

Detailed Description
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The study consisted of an open-label, safety run-in period that was composed of 1 patient cohort with 9 patients/cohort. This phase of the study determined the safety of the capecitabine/ruxolitinib combination in this patient population. A randomized, double-blind study with two treatment arms was conducted once the safety run-in results from the first part of the study showed that the capecitabine/ruxolitinib combination was safe and additional patients could be treated. All patients have received capecitabine therapy in addition to the ruxolitinib or placebo (Study Drug). Treatment for all patients consisted of repeating 21-day cycles. Capecitabine was self-administered for the first 14 days of each cycle, and the Study Drug was self-administered during the entire 21-day cycle. Treatment cycles continued as long as the regimen was tolerated and the patient did not meet any of the discontinuation criteria. In the event of disease progression, capecitabine therapy was discontinued but the Study Drug could continue to be administered. Subjects who discontinued treatment with the Study Drug continued to be followed to obtain information regarding subsequent treatment regimens and survival.

Official Title
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A Randomized Phase 2 Study of Ruxolitinib Efficacy and Safety in Combination With Capecitabine for Subjects With Recurrent or Treatment Refractory Metastatic Pancreatic Cancer (The RECAP Trial)

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Ruxolitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Diagnosis of metastatic pancreatic cancer; subjects must have had measurable, or evaluable disease that was histologically confirmed Karnofsky performance status of ≥ 60 Subjects must have failed 1st-line gemcitabine treatment for metastatic pancreatic cancer: o An alternate chemotherapeutic agent was an acceptable substitute as 1st-line therapy in the event that the subject was intolerant to or ineligible to receive gemcitabine ≥ 2 weeks elapsed from the completion of previous chemotherapy, and subjects must have recovered or been at new stable baseline from any related toxicities Exclusion Criteria: More than 1 prior chemotherapy regimen (not including adjuvant therapy) for metastatic disease Evidence of central nervous system (CNS) metastases (unless stable for > 3 months) or history of uncontrolled seizures Ongoing radiation therapy or prior radiation therapy administered as a second-line treatment Other active malignancy except basal or squamous carcinoma of the skin Inability to swallow food or any condition of the upper GI tract that precluded administration of oral medications Inadequate renal, hepatic and bone marrow function demonstrated by clinical observations and/or laboratory assessments

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capecitabine and ruxolitinib<br> | Drug: Capecitabine<br>* Capecitabine starting dose - 2000 mg/m^2 (1000 mg/m^2 twice a day (BID)) (NOTE: Frequency of administration may be adjusted during the study.)<br>Drug: Ruxolitinib<br>* Ruxolitinib starting dose - 15 mg BID (NOTE: Starting dose of randomized study drug may be 10 mg BID based on results from safety run-in study. Dose of ruxolitinib may be increased during randomized study.)<br>|
| Placebo Comparator: Capecitabine and placebo<br> | Drug: Capecitabine<br>* Capecitabine starting dose - 2000 mg/m^2 (1000 mg/m^2 twice a day (BID)) (NOTE: Frequency of administration may be adjusted during the study.)<br>Drug: Placebo<br>* Placebo matching ruxolitinib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was measured as the length of time (in days) between the randomization date and the date of death. | Primary analysis includes study data from the start of the study (first dose for that subject) until the death of the subject (up to 8 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Progression-free survival was defined as the length of time between the date of randomization and the earlier of death or progressive disease (PD), whichever was earlier, as assessed by RECIST. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Analysis includes study data from the start of the study (first dose for that subject) until death or PD, whichever was earlier up to 8 months. | 
| Objective Response Rate | Objective response rate (ORR) was defined as the percentage of participants with either a confirmed complete response (CR) or partial response (PR) measured by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria during the treatment period. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Measured every 4 weeks for duration of study treatment (up to 8 months) | 
| Durable Response Rate | Durable response was defined as subjects with a response of Partial response (PR) or better at 2 subsequent measurements that were at least 4 weeks apart. | Measured every 4 weeks until death or PD, whichever was earlier (up to 8 months) | 
| Summary of Clinical Benefit | A subject was considered a clinical benefit responder if he/she met at least 1 of the following criteria: Subject showed improvement in at least one of the following parameters on successive scheduled observations without worsening in the others: pain intensity, analgesic use, or performance status Subject was stable or improved on the pain intensity, analgesic use, and performance status and had a ≥ 7% increase in body weight maintained for 2 consecutive reporting periods that was not because of fluid accumulation. | Measured every 4 weeks until death or PD, whichever was earlier (up to 8 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic pancreatic cancer