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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 : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
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 or disease Intervention/treatment Phase
Colon Cancer Rectal Cancer Liver Metastases Drug: Tas-102 Device: SIR-Sphere Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : October 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Safety (adverse events) [ Time Frame: 4 years ]
    Safety (adverse events) of Tas-102 and 90Y radioembolization combination therapy.


Secondary Outcome Measures :
  1. Radiographic response [ Time Frame: 4 years ]
    Radiographic overall response rate (measured in accordance to Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1)

  2. Progression-free survival (PFS) [ Time Frame: 4 years ]
    Progression-free survival (PFS) following Tas-102 and 90Y radioembolization combination therapy (based on radiographic response).

  3. Hepatic progression-free survival (HPFS) [ Time Frame: 4 years ]
  4. Extrahepatic progression free survival (EHPFS) [ Time Frame: 4 years ]
  5. Overall survival (OS) [ Time Frame: 4 years ]
  6. Biomarker response [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 < 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.

Information from the National Library of Medicine

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


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

Locations
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United States, California
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Curt Johanson    415-353-2310    curt.johanson@ucsf.edu   
Principal Investigator: Nicholas Fidelman, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
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Principal Investigator: Nicholas Fidelman, MD University of California, San Francisco
Principal Investigator: Katherine Van Loon, MD University of California, San Francisco

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02602327     History of Changes
Other Study ID Numbers: 16452
First Posted: November 11, 2015    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018

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

Additional relevant MeSH terms:
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Neoplasm Metastasis
Liver Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases