Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases
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|ClinicalTrials.gov Identifier: NCT02602327|
Recruitment Status : Recruiting
First Posted : November 11, 2015
Last Update Posted : November 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Colon Cancer Rectal Cancer Liver Metastases||Drug: Tas-102 Device: SIR-Sphere||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases|
|Actual Study Start Date :||June 27, 2016|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Tas-102 and radioembolization
Combination therapy with Tas-102 and radioembolization using 90Y resin microspheres
Oral nucleoside antitumor agent consisting of α,α,α-trifluorothymidine (FTD) and 5-chloro-6-(2-iminopyrrolidin-1-yl) methyl-2,4 (1H,3H)-pyrimidinedione hydro chloride (TPI) at a molar ratio of 1:0.5.
Other Name: Lonsurf
20-60mm resin microspheres containing Yttrium-90 (90Y, Y90) radioisotope
Other Name: Yttrium-90 (Y90; 90Y) resin microspheres
- Determine dose limiting toxicities (DLT) [ Time Frame: 56 days ]Any adverse events grade ≥ 3 will be reviewed by the treating interventional radiologist and medical oncologist within 24 hours of being informed event. If none of the 3 patients in a cohort experiences a DLT, another 3 patients will be treated at the next higher dose level. However, if 1 of the first 3 patients experiences a DLT, 3 more patients will be treated at the same dose level. The dose escalation will continue until at least 2 patients among a cohort of 3-6 patients experience DLTs (i.e., ≥ 33% of patients with a dose-limiting toxicity at that dose level) or until 3-6 patients had been treated at TAS-102 dose of 35mg/m2 per day in 2 divided doses (up to a maximum of 80 mg per dose) administered concurrently with radioembolization cycles 1 and 2 without experiencing a DLT. DLT window will be 56 days (cycle 1, day 1 to cycle 2, day 28). Dose limiting toxicity will be reached when one of the clinical and/or laboratory parameters are met
- Maximum tolerated dose (MTD) [ Time Frame: Up to 4 years ]Traditional 3+3 design will be used to determine the recommended dose for the dose expansion phase will be defined as the dose level just below this toxic dose level.
- Overall response rate (ORR) [ Time Frame: Up to 4 years ]Radiographic overall response rate (measured in accordance to Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) using imaging. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): 30% decrease in the sum of the longest diameter of target lesionsStable Disease (SD): Small changes that do not meet the criteria for CR, PR, or Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions. ORR will be defined as a ratio of the number of patients who demonstrated complete response (CR) or partial response (PR) to the number of all evaluated patients.
- Progression-free survival (PFS) [ Time Frame: Up to 4 years ]PFS will be defined as a time period that started at enrollment, during which a patient neither progressed nor died based on radiographic response.
- Hepatic progression-free survival (HPFS) [ Time Frame: Up to 4 years ]HPFS will be defined as a time period that started at enrollment, during which a patient neither progressed in the liver nor died based on radiographic response.
- Extrahepatic progression free survival (EHPFS) [ Time Frame: Up to 4 years ]EHPFS will be defined as a time period that started at enrollment, during which a patient neither progressed outside the liver nor died based on radiographic response
- Overall survival (OS) [ Time Frame: Up to 12 months ]Overall Survival will be analyzed 12 months after the last patient is enrolled. Overall survival will be assessed using a two-sided, log-rank test. The survival function will be estimated using the Kaplan-Meier product limit method. In addition, two-sided 95% confidence intervals for the median overall survival will be computed
- Biomarker response [ Time Frame: Up to 4 years ]Proportion of patients with carcinoembryonic antigen (CEA) response with ≥ 50% decline from baseline (in patients with baseline level ≥ 3.2) post combination therapy with Tas-102 and 90Y radioembolization. Maximum percent change will be calculated. CEA level will only be followed for participants with elevated level (≥3.2) at baseline.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02602327
|Contact: Alex Milloy||(415) 502-3310||Alexandra.Milloy@ucsf.edu|
|United States, California|
|University of California San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Alex Milloy 415-502-3310 Alexandra.Milloy@ucsf.edu|
|Principal Investigator: Nicholas Fidelman, MD|
|Principal Investigator:||Nicholas Fidelman, MD||University of California, San Francisco|
|Principal Investigator:||Katherine Van Loon, MD||University of California, San Francisco|