Trial record 2 of 18 for:    tas-102

Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2015 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02602327
First received: November 9, 2015
Last updated: November 10, 2015
Last verified: November 2015
  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).

Condition Intervention Phase
Colon Cancer
Rectal Cancer
Liver Metastases
Drug: Tas-102
Device: SIR-Sphere
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Safety (adverse events) [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Safety (adverse events) of Tas-102 and 90Y radioembolization combination therapy.


Secondary Outcome Measures:
  • Radiographic response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Radiographic overall response rate (measured in accordance to Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1)

  • Progression-free survival (PFS) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) following Tas-102 and 90Y radioembolization combination therapy (based on radiographic response).

  • Hepatic progression-free survival (HPFS) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Extrahepatic progression free survival (EHPFS) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Biomarker response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 24
Study Start Date: September 2016
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tas-102 and radioembolization
Combination therapy with Tas-102 and radioembolization using 90Y resin microspheres
Drug: Tas-102
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
Device: SIR-Sphere
20-60mm resin microspheres containing Yttrium-90 (90Y, Y90) radioisotope
Other Name: Yttrium-90 (Y90; 90Y) resin microspheres

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 < 10 mm in diameter) or combined diameter of all pulmonary nodules > 80 mm.
    • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02602327

Contacts
Contact: Curt Johanson (415) 353-2310 Curt.Johanson@ucsf.edu

Locations
United States, California
University of California San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Nicholas Fidelman, MD University of California, San Francisco
Principal Investigator: Katherine Van Loon, MD University of California, San Francisco
  More Information

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02602327     History of Changes
Other Study ID Numbers: Tas-102 with Radioembolization 
Study First Received: November 9, 2015
Last Updated: November 10, 2015
Health Authority: United States: University of California San Francisco Committee on Human Research

Keywords provided by University of California, San Francisco:
radioembolization
Yttrium-90
90Y
Resin microspheres
Tas-102
Lonsurf
SIR-Sphere

Additional relevant MeSH terms:
Neoplasm Metastasis
Rectal Neoplasms
Liver Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Liver Diseases
Trifluridine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 21, 2016