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

NCT02602327 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 16452NCI-2017-01321
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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).

Conditions

Colon Cancer; Rectal Cancer; Liver Metastases

Keywords

radioembolization; Yttrium-90; 90Y; Resin microspheres; Tas-102; Lonsurf; SIR-Sphere

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  Up to 4 years

Secondary Outcomes (6)

• Overall response rate (ORR)

  Up to 4 years

• Progression-free survival (PFS)

  Up to 4 years

• Hepatic progression-free survival (HPFS)

  Up to 4 years

• Extrahepatic progression free survival (EHPFS)

  Up to 4 years

• Overall survival (OS)

  Up to 12 months

Study Arms (1)

Tas-102 and radioembolization

EXPERIMENTAL

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

Drug: Tas-102; Device: SIR-Sphere

Interventions

Tas-102 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.

Also known as: Lonsurf

Tas-102 and radioembolization

SIR-Sphere DEVICE

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

Also known as: Yttrium-90 (Y90; 90Y) resin microspheres

Tas-102 and radioembolization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 18 years of age or older, and of any ethnic or racial group.
• 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.
• Disease progression or intolerance to at least two prior Food and Drug Administration-approved therapeutic regimens.
• If extrahepatic disease is present, it must be asymptomatic.
• If a primary tumor is in place, it must be asymptomatic.
• Measurable target tumors using standard imaging techniques (RECIST v. 1.1 criteria).
• Tumor replacement \< 50% of total liver volume.
• Current Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 through screening to first treatment on study.
• Completion of prior systemic therapy at least 14 days prior to enrollment.
• Able to understand informed consent.

You may not qualify if:

• 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)
• 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
• Symptomatic lung disease
• Prior therapy with Tas-102.
• Contraindications to Tas-102
• Absolute neutrophil count \< 1,500/μl

Sponsors & Collaborators

• University of California, San Francisco: lead
• Sirtex Medical: collaborator
• Taiho Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• 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.

  PMID: 36514060 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Nicholas Fidelman, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Katherine Van Loon, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2015
• First Posted: November 11, 2015
• Study Start: January 9, 2017
• Primary Completion: May 20, 2021
• Study Completion: August 31, 2021
• Last Updated: August 1, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)