TAS-OX for Refractory Metastatic Colon Cancer
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|ClinicalTrials.gov Identifier: NCT02848079|
Recruitment Status : Active, not recruiting
First Posted : July 28, 2016
Last Update Posted : March 2, 2020
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Neoplasms||Drug: combined TAS-102 and TAS-OX||Phase 1 Phase 2|
TAS-102 is an oral agent, which consists of a combination of a novel antimetabolite 5-trifluorothymidine (FTD) and a thymidine phosphorylase inhibitor (TPI) that prevents degradation of FTD. It has demonstrated activity in chemorefractory metastatic colorectal cancer (mCRC) patients. In the Japanese randomized phase II trial, TAS-102 improved medial overall survival when compared to placebo (9.0 vs.6.6 months, Hazard Ratio (HR) 0.56) in patients with mCRC refractory to 5-fluorouracil (5-FU), irinotecan and oxaliplatin. Subsequently, a randomized phase III study conducted in 13 countries (RECOURSE trial) confirmed this benefit on overall survival when compared to placebo (7.1 months vs. 5.3 months, HR 0.68) in patients with refractory metastatic colorectal cancer (CRC) 5.
Oxaliplatin is a third generation platinum compound, which is active when used together with 5-FU in the treatment of mCRC (FOLFOX). FOLFOX chemotherapy, which is frequently combined with anti-angiogenic agent Bevacizumab, is widely accepted as the preferred first-line regimen in the treatment of this disease in the US. Oxaliplatin is also frequently reintroduced in more advanced settings. Reintroduction is seen after progression on maintenance therapy, after resolution of previous treatment limiting neuropathy, after disease recurrence post adjuvant treatment or post metastasectomy. In the control arm of a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer (OPTIMOX1 study), oxaliplatin was reintroduced in 27% of patients. Although patients derive clinical benefit when oxaliplatin is reintroduced, the response rates are not as robust as during initial exposures. Decreased efficacy may be at least in part due to prolonged exposure and resultant resistance to 5-FU, which is a backbone in maintenance and in oxaliplatin containing regimens. Hence, the investigators propose exploring the safety and efficacy of oxaliplatin in combination with an alternative anti-metabolite TAS-102 (TAS-OX).
TAS-102 has demonstrated activity in 5-FU refractory mCRC, so the investigators hypothesize that TAS-OX may serve as an alternative drug combination for patients who have progressed or recurred after FOLFOX, and who are candidates for additional oxaliplatin therapy.
This is a 2-part clinical trial with TAS-102 in combination with oxaliplatin. The first part will be a dose-finding run-in phase and will enroll 3-18 patients. The second part, the focus of this study, will be a single arm cohort , which will further evaluate the safety, as well as efficacy, of TAS-OX in the treatment of mCRC. The subjects in part 2 will be treated with the drug doses determined in Part 1 of the trial. Up to 50 patients will be enrolled in part 2. Anticipated enrollment may be as high as 68 patients. Maximum potential enrollment is listed under anticipated enrollment, below.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||68 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||TAS-102 and Oxaliplatin (TAS-OX) for Refractory Metastatic Colon Cancer|
|Study Start Date :||August 2016|
|Estimated Primary Completion Date :||July 1, 2020|
|Estimated Study Completion Date :||December 2021|
Experimental: combined TAS-102 and oxaliplatin
Combination treatment with TAS-102 and oxaliplatin
Drug: combined TAS-102 and TAS-OX
Combination treatment with TAS-102 and oxaliplatin. TAS-102 is an oral medication; oxaliplatin (TAS-OX) is given by infusion.
- Overall Response Rate measured by Response Evaluation Criteria In Solid Tumor (RECIST) 1.1 criteria [ Time Frame: up to 30 days following discontinuation of treatment ]
- Progression Free Survival assessed according to RECIST criteria version 1.1. [ Time Frame: from the date of start of treatment to the date of first documented progression or any cause of death assessed up to 12 months. ]
- Overall Survival assessed by time to death from start of study [ Time Frame: from the date of start of treatment to the date of any cause of death assessed up to 24 months. ]
- safety and tolerability assessed with Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: assessed from start of treatment up to discontinuation of treatment or up to 12 months. ]
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): NCT02848079
|United States, Connecticut|
|Yale Cancer Center|
|New Haven, Connecticut, United States, 06510|
|Principal Investigator:||Jeremy S. Kortansky, M.D.||Yale University|