An Open-Label Study of Ruxolitinib Given With Chemotherapy in Patients With Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT01822756|
Recruitment Status : Terminated (Dose escalation ended after Cohort B1, RUX 10 mg BID - GCSF in October 2014.)
First Posted : April 2, 2013
Results First Posted : April 13, 2017
Last Update Posted : February 12, 2018
This is a study of ruxolitinib in combination with gemcitabine with or without nab-paclitaxel administered to patients with advanced or metastatic pancreatic cancer. The study will be conducted in two parts.
Part 1 of the study will evaluate the safety, tolerability and pharmacokinetics (PK) of ruxolitinib when given as described to patients with advanced or metastatic pancreatic cancer. A goal of Part 1 will be to identify the maximally tolerated dose (MTD) of ruxolitinib when given with gemcitabine with or without nab-paclitaxel. This dose will be selected for use in Part 2 of the study.
Part 2 of the study will further evaluate the safety, tolerability, PK and preliminary clinical activity of ruxolitinib at the dose defined in Part 1 used in combination with gemcitabine with or without nab-paclitaxel in subjects with advanced or metastatic pancreatic cancer.
After multiple challenges of trial conduct, by mutual agreement between investigators and sponsor, dose escalation ended after Cohort B1, RUX 10 mg twice daily (BID) - GCSF in October 2014. Therefore, the MTD was not reached. No safety issues led to the decision to stop further enrollment.
Because of the early study termination, samples for pharmacokinetics and pharmacodynamics, and computed tomography for tumor burden were collected, but not analyzed; analysis data are not available. The data cutoff for this posting is 22 SEP 2015. As of the data cutoff, 1 subject was receiving treatment in the study and had been enrolled for 47 weeks. This subject had their end of treatment visit in AUG 2016. A comparison of this subjects' safety data after the cutoff date showed no clinically meaningful differences (eg, adverse events) compared with safety results that are summarized here.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumors Pancreatic Cancer||Drug: ruxolitinib Drug: gemcitabine Drug: nab-paclitaxel Drug: filgrastim||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b Study of the Safety and Tolerability of Ruxolitinib in Combination With Gemcitabine With or Without Nab-Paclitaxel in Subjects With Advanced Solid Tumors|
|Study Start Date :||April 2013|
|Actual Primary Completion Date :||September 2015|
|Actual Study Completion Date :||August 2016|
Experimental: Regimen A -ruxolitinib, gemcitabine
Ruxolitinib (RUX) was self-administered by the subject orally in the morning and evening, approximately 12 hours apart, without regard to food. The morning dose of RUX was to be taken before the chemotherapy infusion, Gemcitabine IV, on days when they were given together (Days 1, 8, and 15 of each cycle).
Other names: Gemzar®
Experimental: Regimen B-ruxolitinib, gemcitabine, nab-paclitaxel, filgrastim
Ruxolitinib (RUX) was self-administered by the subject orally in the morning and evening, approximately 12 hours apart, without regard to food.
Gemcitabine was provided as open-label, commercial product and was administered intravenously (IV) over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. Reduced doses of gemcitabine administered IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle could also be explored.
nab-Paclitaxel, as open-label, commercial product, was administered IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle.
Other names: Gemzar®
Other names: Abraxane®
Prophylactic GCSF support was filgrastim and was given in Cycle 1 on Days 2 to 5, 9 to 12, and 16 to 19, unless chemotherapy was held for toxicity, then prophylactic GCSF support was also held.
Other Name: Neupogen®
- Percentage of Participants With Adverse Events That Are Defined as Dose Limiting Toxicities (DLTs) [ Time Frame: Approximately 28 days ]Toxicities occurring during the first treatment cycle (Cycle 1) defined tolerability. Within each cohort, subjects were considered evaluable if they had received at least 40 of 56 planned doses of RUX during the 28-day surveillance period and received 2 of the 3 planned doses of chemotherapy (gemcitabine and/or gemcitabine and nab-paclitaxel) at the assigned dose level, or they had experienced a DLT.
- Plasma Concentrations Will be Used to Estimate Peak Plasma Concentration (Cmax) and Area Under the Plasma Concentration Curve (AUC). [ Time Frame: Day 1 and Day 8 ]
- Plasma Concentration of Tumor Specific Biomarkers and Cytokines Before and During Treatment. [ Time Frame: Up to 6 months ]
- Clinical Activity as Measured by the Greatest Decrease in Tumor Burden Compared to Baseline. [ Time Frame: Approximately 6 months ]
- Percentage of Participants With a Best Response by RECIST Criteria [ Time Frame: every 2 cycles starting at Cycle 3 Day 1 up to approximately 4 to 6 months ]
Best response was determined on the subject level using the highest overall response achieved post-baseline. In the case of stable disease (SD), measurements had to meet the SD criterion at least once after study entry at a minimum interval of 49 days. Subjects who failed to meet this criterion had best response of progressive disease (PD) if the next available RECIST evaluation after the initial scan indicated PD or not evaluable (NE) if no additional RECIST evaluations were available.
Complete Response (CR) and Partial Response (PR) defined by the Response Evaluation Criteria in Solid Tumor (RECIST) criteria. CR: Disappearance of all target and nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, or persistence of 1 or more nontarget lesion(s) or/and maintenance of tumor marker level above the normal limits.
- Percentage of Responders [ Time Frame: Randomization to clinical cutoff 22Sept2015 (approx 244 days) ]Duration of response was measured as the time from the first overall response contributing to an objective response to the first overall response of progressive disease (PD) occurring after the first overall response contributing to the objective response.
- Duration of Response [ Time Frame: Randomization to clinical cutoff 22Sept2015 (approx 244 days) ]Duration of response was the time from the first overall response contributing to an objective response to the first overall response of progressive disease (PD) occurring after the first overall response contributing to the objective response. Confidence intervals for median duration of response were calculated using the method of Brookmeyer and Crowley (1982).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01822756
|United States, Alabama|
|Birmingham, Alabama, United States|
|United States, Florida|
|Gainesville, Florida, United States|
|Sarasota, Florida, United States|
|United States, North Carolina|
|Durham, North Carolina, United States|
|United States, Tennessee|
|Nashville, Tennessee, United States|
|Study Director:||Fitzroy Dawkins, M.D.||Incyte Corporation|