San Francisco, California 94143


Purpose:

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).


Study summary:

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.


Criteria:

Inclusion Criteria: 1. Male or female, 18 years of age or older, and of any ethnic or racial group. 2. Diagnosis of unresectable metastatic colorectal adenocarcinoma with liver-dominant bilobar disease. Diagnosis may be made by histo- or cyto-pathology, or by clinical and imaging criteria. 3. Disease progression or intolerance to at least two prior Food and Drug Administration-approved therapeutic regimens. 4. If extrahepatic disease is present, it must be asymptomatic. 5. If a primary tumor is in place, it must be asymptomatic. 6. Measurable target tumors using standard imaging techniques (RECIST v. 1.1 criteria). 7. Tumor replacement < 50% of total liver volume. 8. Current Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 through screening to first treatment on study. 9. Completion of prior systemic therapy at least 14 days prior to enrollment. 10. Able to understand informed consent. Exclusion Criteria: 1. At risk of hepatic or renal failure - Serum creatinine > 1.5 mg/dl - Serum bilirubin > 1.3 mg/ml - Albumin < 2.0 g/dL - Aspartate and/or alanine aminotransferase level > 5 times upper normal limit - Any history of hepatic encephalopathy - Cirrhosis or portal hypertension - Clinically evident ascites (trace ascites on imaging is acceptable) 2. Contraindications to angiography and selective visceral catheterization - Any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device) - Severe allergy or intolerance to contrast agents, narcotics, or sedatives that cannot be managed medically 3. Symptomatic lung disease 4. Prior therapy with Tas-102. 5. Contraindications to Tas-102 - Absolute neutrophil count < 1,500/μl - Platelet count < 75,000/μl - Allergy or intolerance to Tas-102 6. Unresolved toxicity of greater than or equal to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 2 due to prior therapies. 7. Evidence of potential delivery of - Greater than 30 Gy absorbed dose of radiation to the lungs during a single 90Y resin microsphere administration; or - Cumulative delivery of radiation to the lungs > 50 Gy over multiple treatments. 8. Evidence of any detectable Tc-99m macro aggregated albumin flow to the stomach or duodenum, after application of established angiographic techniques to stop such flow. 9. Previous radiation therapy to the lungs and/or to the upper abdomen 10. Any prior arterial liver-directed therapy, including chemoembolization, bland embolization, and 90Y radioembolization 11. Any intervention for, or compromise of the ampulla of Vater 12. Active uncontrolled infection. Presence of latent or medication-controlled HIV and/or viral hepatitis is allowed. 13. Significant extrahepatic disease - Symptomatic extrahepatic disease (including primary tumor, if unresected). - Greater than 10 pulmonary nodules (each < 20 mm in diameter) or combined diameter of all pulmonary nodules > 15 cm. - Peritoneal carcinomatosis 14. Life expectancy less than 3 months 15. Pregnant or lactating female 16. In the investigator's judgment, any co-morbid disease or condition that would place the patient at undue risk and preclude safe use of radioembolization or Tas-102.


NCT ID:

NCT02602327


Primary Contact:

Principal Investigator
Nicholas Fidelman, MD
University of California, San Francisco

Alex Milloy
Phone: (415) 502-3310
Email: Alexandra.Milloy@ucsf.edu


Backup Contact:

N/A


Location Contact:

San Francisco, California 94143
United States

Alex Milloy
Phone: 415-502-3310
Email: Alexandra.Milloy@ucsf.edu

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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