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

NCT ID: NCT02602327

Last Updated: 2022-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-09
• Study Completion Date: 2021-08-31

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).

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.

Conditions

Colon Cancer; Rectal Cancer; Liver Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tas-102 and radioembolization

Combination therapy with Tas-102 and radioembolization using 90Y resin microspheres

Group Type: EXPERIMENTAL

Tas-102

Intervention Type: DRUG

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.

SIR-Sphere

Intervention Type: DEVICE

20-60mm resin microspheres containing Yttrium-90 (90Y, Y90) radioisotope

Interventions

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.

Intervention Type: DRUG

SIR-Sphere

20-60mm resin microspheres containing Yttrium-90 (90Y, Y90) radioisotope

Intervention Type: DEVICE

Other Intervention Names

Lonsurf; Yttrium-90 (Y90; 90Y) resin microspheres

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sirtex Medical

INDUSTRY

Sponsor Role: collaborator

Taiho Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicholas Fidelman, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Katherine Van Loon, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California San Francisco

San Francisco, California, United States

Countries

United States

References

Fidelman N, Atreya CE, Griffith M, Milloy MA, Carnevale J, Cinar P, Venook AP, Van Loon K. Phase I prospective trial of TAS-102 (trifluridine and tipiracil) and radioembolization with 90Y resin microspheres for chemo-refractory colorectal liver metastases. BMC Cancer. 2022 Dec 13;22(1):1307. doi: 10.1186/s12885-022-10401-0.

Reference Type: DERIVED

PMID: 36514060 (View on PubMed)

Other Identifiers

NCI-2017-01321

Identifier Type: REGISTRY

Identifier Source: secondary_id

16452

Identifier Type: -

Identifier Source: org_study_id