Pancreatic Cancer
Conditions
Keywords
Metastatic pancreatic cancer
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.
Interventions
DRUGCapecitabine
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.)
DRUGRuxolitinib
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.)
DRUGPlacebo
Placebo matching ruxolitinib
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 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 | 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 | 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 | 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. |
Countries
United States
Participant flow
Recruitment details
The open-label, safety run-in (1 cohort) was designed to confirm the safety of the combination of ruxolitinib and capecitabine in subjects with advanced or metastatic adenocarcinoma of the pancreas. The double-blind portion was 2 treatment groups randomized 1:1: ruxolitinib plus capecitabine or matching placebo plus capecitabine.
Participants by arm
| Arm | Count |
|---|---|
| Ruxolitinib - Safety Run-In Subjects received capecitabine 2000 mg/m\^2 (1000 mg/m\^2 twice a day \[BID\]) + ruxolitinib at 15 mg BID. | 9 |
| Ruxolitinib Subjects received ruxolitinib 15 mg BID plus capecitabine at a starting dose of 2000 mg/m\^2 (1000 mg/m\^2 twice a day \[BID\]). | 64 |
| Placebo Matching placebo tablets were administered as oral doses in the same manner as active drug during the randomized portion of the study. Capecitabine starting dose - 2000 mg/m\^2 (1000 mg/m\^2 twice a day \[BID\]). | 63 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized | Adverse Event | 4 | 10 |
| Randomized | Death | 1 | 0 |
| Randomized | Other - unspecified | 37 | 31 |
| Randomized | Patient decision | 5 | 9 |
| Randomized | Physician Decision | 16 | 13 |
| Safety Run-In | Adverse Event | 3 | 0 |
| Safety Run-In | Death | 1 | 0 |
| Safety Run-In | Disease progression | 3 | 0 |
| Safety Run-In | Patient decision | 1 | 0 |
| Safety Run-In | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Ruxolitinib - Safety Run-In | Ruxolitinib | Placebo |
|---|---|---|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 9.5 | 61.6 years STANDARD_DEVIATION 9.4 | 65.7 years STANDARD_DEVIATION 9.3 | 66.3 years STANDARD_DEVIATION 9.8 |
| Body mass index (BMI) | 24.789 kg/m^2 STANDARD_DEVIATION 5.394 | 25.3 kg/m^2 STANDARD_DEVIATION 4.209 | 25.354 kg/m^2 STANDARD_DEVIATION 6.332 | 24.243 kg/m^2 STANDARD_DEVIATION 4.237 |
| Body surface area | 1.827 m^2 STANDARD_DEVIATION 0.275 | 1.869 m^2 STANDARD_DEVIATION 0.287 | 1.863 m^2 STANDARD_DEVIATION 0.297 | 1.791 m^2 STANDARD_DEVIATION 0.248 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 0 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 129 Participants | 9 Participants | 62 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Height | 169.78 cm STANDARD_DEVIATION 11.18 | 171.67 cm STANDARD_DEVIATION 14.11 | 171.29 cm STANDARD_DEVIATION 11.93 | 168.27 cm STANDARD_DEVIATION 10.25 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 3 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 113 Participants | 5 Participants | 54 Participants | 54 Participants |
| Sex: Female, Male Female | 57 Participants | 5 Participants | 23 Participants | 29 Participants |
| Sex: Female, Male Male | 79 Participants | 4 Participants | 41 Participants | 34 Participants |
| Weight | 72.156 kg STANDARD_DEVIATION 19.427 | 75.051 kg STANDARD_DEVIATION 17.317 | 75.014 kg STANDARD_DEVIATION 21.914 | 69.299 kg STANDARD_DEVIATION 16.26 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 9 | 57 / 59 | 59 / 60 |
| serious Total, serious adverse events | 5 / 9 | 32 / 59 | 35 / 60 |
Outcome results
Primary
Overall Survival
Overall survival was measured as the length of time (in days) between the randomization date and the date of death.
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).
Population: The intent-to-treat (ITT) population included subjects randomized in Part 2 of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib | Overall Survival | 136.5 days |
| Placebo | Overall Survival | 129.5 days |
p-value: 0.049495% CI: [0.506, 1.061]Log Rank
Comparison: Cox Regression Analysis of Overall Survival: C-reactive protein (CRP) \> 13 μg/ml; Statistical analysis plan (SAP) specified subgroup analysisp-value: 0.008195% CI: [0.281, 0.888]Log Rank
Secondary
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.
Time frame: Measured every 4 weeks until death or PD, whichever was earlier (up to 8 months)
Population: The intent-to-treat (ITT) population included subjects randomized in Part 2 of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib | Durable Response Rate | 7.8 percentage of participants |
| Placebo | Durable Response Rate | 0.0 percentage of participants |
p-value: 0.0236Pearson's chi-square test
Secondary
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.
Time frame: Measured every 4 weeks for duration of study treatment (up to 8 months)
Population: The intent-to-treat (ITT) population included subjects randomized in Part 2 of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Objective Response Rate | Overall response | 7.8 percentage of participants |
| Ruxolitinib | Objective Response Rate | Complete response | 1.6 percentage of participants |
| Ruxolitinib | Objective Response Rate | Partial response | 6.3 percentage of participants |
| Placebo | Objective Response Rate | Overall response | 1.6 percentage of participants |
| Placebo | Objective Response Rate | Complete response | 0.0 percentage of participants |
| Placebo | Objective Response Rate | Partial response | 1.6 percentage of participants |
Secondary
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
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.
Population: The intent-to-treat (ITT) population included subjects randomized in Part 2 of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib | Progression-Free Survival (PFS) | 51.0 days |
| Placebo | Progression-Free Survival (PFS) | 46.0 days |
p-value: 0.13495% CI: [0.513, 1.094]Cox proportional hazards model
Secondary
Summary of Clinical Benefit
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.
Time frame: Measured every 4 weeks until death or PD, whichever was earlier (up to 8 months)
Population: The intent-to-treat (ITT) population included subjects randomized in Part 2 of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Summary of Clinical Benefit | Pain intensity - Improved | 10.9 percentage of participants |
| Ruxolitinib | Summary of Clinical Benefit | Karnofsky performance status - Improved | 3.1 percentage of participants |
| Ruxolitinib | Summary of Clinical Benefit | Analgesic use - Improved | 4.7 percentage of participants |
| Ruxolitinib | Summary of Clinical Benefit | Body weight - Improved | 3.1 percentage of participants |
| Ruxolitinib | Summary of Clinical Benefit | Subjects with clinical benefit | 12.5 percentage of participants |
| Placebo | Summary of Clinical Benefit | Body weight - Improved | 0.0 percentage of participants |
| Placebo | Summary of Clinical Benefit | Subjects with clinical benefit | 1.6 percentage of participants |
| Placebo | Summary of Clinical Benefit | Pain intensity - Improved | 1.6 percentage of participants |
| Placebo | Summary of Clinical Benefit | Analgesic use - Improved | 0.0 percentage of participants |
| Placebo | Summary of Clinical Benefit | Karnofsky performance status - Improved | 0.0 percentage of participants |