Study of Ruxolitinib in Pancreatic Cancer Patients (RECAP)

• ClinicalTrials.gov Identifier: NCT01423604
• Recruitment Status: Completed
• First Posted: August 26, 2011
• Results First Posted: August 29, 2016
• Last Update Posted: February 12, 2018
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: August 22, 2011
• First Posted Date: August 26, 2011
• Results First Submitted Date: April 1, 2016
• Results First Posted Date: August 29, 2016
• Last Update Posted Date: February 12, 2018
• Study Start Date: July 2011
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 19, 2016)

Overall Survival [ Time Frame: 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). ]

Overall survival was measured as the length of time (in days) between the randomization date and the date of death.

• Original Primary Outcome Measures (submitted: August 24, 2011): Overall survival [ Time Frame: Randomization through discontinuation or death (approximately over the course of five months) ]

Current Secondary Outcome Measures (submitted: July 19, 2016)

• Progression-Free Survival (PFS) [ Time Frame: 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. ]
  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
• Objective Response Rate [ Time Frame: Measured every 4 weeks for duration of study treatment (up to 8 months) ]
  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.
• Durable Response Rate [ Time Frame: Measured every 4 weeks until death or PD, whichever was earlier (up to 8 months) ]
  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.
• Summary of Clinical Benefit [ Time Frame: Measured every 4 weeks until death or PD, whichever was earlier (up to 8 months) ]
  A subject was considered a clinical benefit responder if he/she met at least 1 of the following criteria:

  1. 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
  2. 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.

Original Secondary Outcome Measures (submitted: August 24, 2011)

• Evaluate efficacy of ruxolitinib treatment in combination with capecitabine based on tumor response rate [ Time Frame: Measured approximately every 3 weeks from baseline through study discontinuation (approximately over the course of five months) ]
• Evaluate efficacy of ruxolitinib in combination with capecitabine for patient reported quality of life [ Time Frame: Measured approximately every 3 weeks from baseline through study discontinuation (approximately over the course of five months) ]
• Evaluate efficacy of ruxolitinib treatment in combination with capecitabine for pain status [ Time Frame: Measured approximately every 3 weeks from baseline through study discontinuation (approximately over the course of five months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Ruxolitinib in Pancreatic Cancer Patients
• Official Title: 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)
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• Drug: Capecitabine
  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.)
• Drug: Ruxolitinib
  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.)
• Drug: Placebo
  Placebo matching ruxolitinib

Study Arms

• Experimental: Capecitabine and ruxolitinib
  Interventions:

  • Drug: Capecitabine
  • Drug: Ruxolitinib
• Placebo Comparator: Capecitabine and placebo
  Interventions:

  • Drug: Capecitabine
  • Drug: Placebo

• Publications *: Hurwitz HI, Uppal N, Wagner SA, Bendell JC, Beck JT, Wade SM 3rd, Nemunaitis JJ, Stella PJ, Pipas JM, Wainberg ZA, Manges R, Garrett WM, Hunter DS, Clark J, Leopold L, Sandor V, Levy RS. Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed. J Clin Oncol. 2015 Dec 1;33(34):4039-47. doi: 10.1200/JCO.2015.61.4578. Epub 2015 Sep 8.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 19, 2016): 136
• Original Estimated Enrollment (submitted: August 24, 2011): 138
• Actual Study Completion Date: November 2016
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01423604
• Other Study ID Numbers: 18424-262
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: William Williams, MD; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: January 2018