Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer
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ClinicalTrials.gov Identifier: NCT02368886 |
Recruitment Status :
Completed
First Posted : February 23, 2015
Results First Posted : July 26, 2019
Last Update Posted : July 27, 2023
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Tracking Information | |||||||
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First Submitted Date ICMJE | February 16, 2015 | ||||||
First Posted Date ICMJE | February 23, 2015 | ||||||
Results First Submitted Date ICMJE | June 6, 2019 | ||||||
Results First Posted Date ICMJE | July 26, 2019 | ||||||
Last Update Posted Date | July 27, 2023 | ||||||
Actual Study Start Date ICMJE | March 27, 2015 | ||||||
Actual Primary Completion Date | September 1, 2017 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Proportion of Patients in Each Arm Who Complete 2 Cycles of Protocol Treatment and Initiate Cycle 3 [ Time Frame: At 8 weeks ] Fisher exact test will be used to detect a difference course 3 between arms (starting low dose [pooled arm A1 and A2] versus [vs.] standard dose [pooled arm B1 and B2]). The proportion of patients who complete 2 courses of protocol treatment and initiate course 3 will be computed by arm with its 95% confidence interval using exact method.
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Original Primary Outcome Measures ICMJE |
Proportion of patients in each arm who complete 2 courses of treatment and who intend to initiate course 3 if no progression is noted on the planned disease evaluation [ Time Frame: At 8 weeks ] Fisher exact test will be used to detect a difference in 8-week planned continuation rates between treatment strategies, and 8-week planned continuation rates with 95% confidence intervals will be computed overall and within each treatment arm. A comparison of the primary endpoint (8 week planned discontinuation rate) between clobetasol propionate strategies (1 vs. 2) will also be performed, using a stratified Fisher Exact test, where the comparison is stratified by regorafenib strategy (A vs. B).
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
Pharmacokinetics (PK) Parameters of Regorafenib Using Liquid Chromatography Mass Spectrometry [ Time Frame: Baseline, prior to treatment, days 7, 14, and 21 prior to treatment (course 1), and days 1 and 21 prior to treatment (course 2) ] After quantitation, the average trough concentration, calculated from all available data, will be calculated. This average trough concentration will be correlated with toxicity and efficacy endpoints. Further descriptive characteristics of the pharmacokinetics will also be calculated, an example includes (but is not limited to) within-patient variability in the trough concentrations pharmacokinetic parameters will also be calculated, both overall and within courses, as a ratio of the maximum:minimum value.
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Original Other Pre-specified Outcome Measures |
PK parameters of regorafenib using liquid chromatography mass spectrometry (average trough concentration) [ Time Frame: Baseline, prior to treatment, days 7, 14, and 21 prior to treatment (course 1), and days 1 and 21 prior to treatment (course 2) ] After quantitation, the average trough concentration, calculated from all available data, will be calculated. This average trough concentration will be correlated with toxicity and efficacy endpoints. Further descriptive characteristics of the pharmacokinetics will also be calculated, An example includes (but is not limited to) within-patient variability in the trough concentrations pharmacokinetic parameters will also be calculated, both overall and within cycles, as a ratio of the maximum:minimum value.
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Descriptive Information | |||||||
Brief Title ICMJE | Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer | ||||||
Official Title ICMJE | Regorafenib Dose Optimization Study (ReDOS): A Phase II Randomized Study of Lower Dose Regorafenib Compared to Standard Dose Regorafenib in Patients With Refractory Metastatic Colorectal Cancer (mCRC) | ||||||
Brief Summary | This randomized phase II trial studies how well lower-dose compared to standard dose regorafenib works in treating patients with colorectal cancer that has spread from the primary site (place where it started) to other places in the body and does not respond to treatment. Regorafenib may stop the growth of colorectal cancer by blocking the growth of new blood vessels necessary for tumor growth and by blocking some of the enzymes needed for cell growth. It is not yet known whether lower-dose or standard dose regorafenib is more effective in treating patients with colorectal cancer. Clobetasol propionate is a steroid cream that is commonly used to treat a variety of skin conditions and may help prevent hand-foot skin reactions in patients receiving regorafenib. | ||||||
Detailed Description | PRIMARY OBJECTIVES: I. Evaluate the proportion of patients who complete 2 cycles of protocol treatment and initiate cycle 3 in arm A (pooled arm A1 and A2) and arm B (pooled arm B1 and B2). SECONDARY OBJECTIVES: I. Evaluate outcome measures for efficacy in each arm including progression-free survival (PFS), time to progression (TTP), and overall survival (OS). II. Compare between arms the cumulative dose and dose intensity received within the first two cycles. III. Evaluate the proportion of patients in each arm that exhibit grade 3 palmar-plantar erythrodysesthesia syndrome (PPES) and/or fatigue, and make comparisons between regorafenib dosing strategies and pre-emptive versus (vs.) reactive strategies to address PPES. IV. Compare quality of life (QOL) between treatment arms (regorafenib dosing strategies and preemptive vs. reactive PPES strategies) as measured by the Hand and Foot Syndrome (HFS)14, Brief Fatigue Inventory (BFI), and Linear Analogue Self-Assessment (LASA) questionnaires. TERTIARY OBJECTIVES: I. Evaluate and compare trough minimum concentration (Cmin) pharmacokinetics (PK) during the first 2 treatment cycles for regorafenib and active metabolites M2, M5 between the low dose (dose escalation) and the standard dose cohorts, and correlate with toxicity profile. II. Evaluate the correlation between PK parameters and tumor response/stable disease after the first two cycles. III. Evaluate the correlation between PK parameters and PFS and OS. IV. Evaluate if trough (Cmin) concentrations are associated with patient-specific factors (such as ? but not limited to ? age and concomitant medications). OUTLINE: Patients are randomized to 1 of 4 treatment arms. ARM A1: Patients receive lower-dose regorafenib PO once daily (QD) on days 1-21 and pre-emptive clobetasol propionate given topically twice daily (BID) for 12 weeks, beginning on day 1 of regorafenib. ARM A2: Patients receive lower-dose regorafenib PO as in Arm A1 and reactive clobetasol propionate given topically BID beginning on day 1 per physician discretion upon occurrence of PPES grade >= 1. ARM B1: Patients receive standard dose regorafenib PO QD on days 1-21 and pre-emptive clobetasol propionate as in Arm A1. ARM B2: Patients receive standard dose regorafenib PO as in Arm B1 and reactive clobetasol propionate as in Arm A2. In all arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 2-6 months. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Completed | ||||||
Actual Enrollment ICMJE |
123 | ||||||
Original Estimated Enrollment ICMJE |
120 | ||||||
Actual Study Completion Date ICMJE | March 2, 2023 | ||||||
Actual Primary Completion Date | September 1, 2017 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
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Administrative Information | |||||||
NCT Number ICMJE | NCT02368886 | ||||||
Other Study ID Numbers ICMJE | RU021407I NCI-2015-00011 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) RU021407I ( Other Identifier: Academic and Community Cancer Research United ) P30CA015083 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||
Current Responsible Party | Academic and Community Cancer Research United | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Academic and Community Cancer Research United | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||||
Investigators ICMJE |
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PRS Account | Academic and Community Cancer Research United | ||||||
Verification Date | September 2022 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |