A Phase 1 interventional study of Tas-102 and SIR-Sphere in Colon Cancer, Rectal Cancer and Liver Metastases, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-08-01.
Sponsored by University of California, San Francisco · Phase 1, Interventional, and Treatment
This is a phase I dose escalation study (3+3 design) with a dose expansion arm (12 patients) designed to evaluate safety of the combination of Tas-102 and radioembolization using Yttrium-90 (90Y) resin microspheres for patients with chemotherapy-refractory liver-dominant chemotherapy-refractory metastatic colorectal cancer (mCRC).
Randomized studies have demonstrated that Tas-102 has single agent activity against chemotherapy refractory colorectal cancer. A recent pre-clinical study has shown that Tas-102 may have activity as a radiation sensitizer in bladder cancer cell lines. Benefit of single agent Tas-102 against chemotherapy refractory colon cancer and the drug's promise a radiosensitizer make Tas-102 a potential candidate drug for testing in combination with radioembolization using Yttrium-90 resin microspheres in patients with liver-dominant chemotherapy-refractory mCRC. This is a phase I dose escalation study with a dose expansion arm designed to evaluate safety of the combination of Tas-102 and radioembolization using 90Y resin microspheres for patients with chemotherapy-refractory colon or rectal adenocarcinoma metastatic to the liver.
3,517 studies on the registry are indexed under Neoplasm Metastasis; 885 are open to participants now.
This study's enrollment of 21 is below the median of 54 across 2,767 interventional studies indexed under Neoplasm Metastasis.
Browse Neoplasm Metastasis studies →University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.
Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.
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Exclusion Criteria:
At risk of hepatic or renal failure
Contraindications to angiography and selective visceral catheterization
Contraindications to Tas-102
Evidence of potential delivery of
Significant extrahepatic disease
Combination therapy with Tas-102 and radioembolization using 90Y resin microspheres
Drug: Tas-102 · Device: SIR-Sphere
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.
Also known as: Lonsurf
20-60mm resin microspheres containing Yttrium-90 (90Y, Y90) radioisotope
Also known as: Yttrium-90 (Y90; 90Y) resin microspheres
Determine dose limiting toxicities (DLT)
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
Time frame: 56 days
Maximum tolerated dose (MTD)
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.
Time frame: Up to 4 years
Overall response rate (ORR)
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.
Time frame: Up to 4 years
Progression-free survival (PFS)
PFS will be defined as a time period that started at enrollment, during which a patient neither progressed nor died based on radiographic response.
Time frame: Up to 4 years
Hepatic progression-free survival (HPFS)
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.
Time frame: Up to 4 years
Extrahepatic progression free survival (EHPFS)
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
Time frame: Up to 4 years
Overall survival (OS)
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
Time frame: Up to 12 months
Biomarker response
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.
Time frame: Up to 4 years
Plan to share: No
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University of California, San Francisco