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.
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): 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|