TAS-102 and Irinotecan in 2L+ Gastric and Gastroesophageal Adenocarcinoma

NCT04074343 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: UCI 18-125 [HS# 2019-5179]2019-5179
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase Ib single-arm, open-label clinical trial determining the feasibility and efficacy of TAS-102 and irinotecan in subjects with advanced gastric and gastroesophageal adenocarcinoma. These are subjects who are not candidates for curative treatments and who have received at least one prior line of chemotherapy with a fluoropyrimidine and platinum agent.

Conditions

Gastric Adenocarcinoma; GastroEsophageal Cancer

Keywords

Gastric Adenocarcinoma; TAS-102; Irinotecan; Gastroesophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Progression-free Survival at 6 Months

  This is defined as the percentage of subjects who are free of progression 6 months after study treatment start. Progression is defined as death, radiographic progression or clinical deterioration attributed to disease progression as judged by an investigator. Radiographic progression is defined using the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions and an absolute increase of an least 5 mm and/or appearance of new lesions.

  6 Months

Secondary Outcomes (3)

• Number of Participants With Grade 3-5 Adverse Events

  8 Weeks

• Objective Response Rate as Assessed by RECIST v1.1 Criteria of Patients Who Received TAS-102 and Irinotecan

  From date of registration until first date of disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

• Overall Survival of Patients of Patients Who Received TAS-102 and Irinotecan

  From date of registration for up to 18 months after last patient is enrolled or until death from any cause, whichever came first.

Study Arms (1)

TAS-102 and Irinotecan

EXPERIMENTAL

Patients receive TAS-102 25 mg/m2 PO twice daily on days 1-5 and and Irinotecan 180mg/m2 IV on day 1 every 14 days.

Drug: TAS-102; Drug: Irinotecan

Interventions

TAS-102 DRUG

Given PO

Also known as: LONSURF, trifluoridine and tipiracil

TAS-102 and Irinotecan

Irinotecan DRUG

Given IV

Also known as: CAMPTOSAR, CPT-11

TAS-102 and Irinotecan

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed gastric or gastroesophageal adenocarcinoma
• Must have locally advanced, recurrent, or metastatic disease not amenable to curative intent surgery.
• Must have progressed, or not tolerated, at least one line of treatment with a platinum and/or fluoropyrimidine containing regimen. At least one cycle of combination chemotherapy including a platinum (oxaliplatin, cisplatin, carboplatin) and/or fluoropyrimidine (capecitabine or 5-Fluorouracil) based regimen for advanced disease. Combination regimens with platinum/fluoropyrimidine containing a taxane and or a checkpoint inhibitor are allowed. Patients progressing within six months of perioperative chemotherapy or definitive chemoradiation for localized disease are eligible. Patients who have exhausted all other standard of care options are also eligible.
• Age ≥ 18 years
• Performance status: ECOG performance status ≤2
• Life expectancy of greater than 3 months
• Adequate organ and marrow function as defined below:
• leukocytes : ≥ 3,000/mcL
• absolute neutrophil count: ≥ 1,500/mcL
• platelets: ≥ 80,000/mcl
• total bilirubin: within normal institutional limits
• AST(SGOT)/ALT(SPGT): ≤ 3 X institutional upper limit of normal or ≤ 5 X if liver metastases are present
• creatinine: \< 1.5 X upper limit of normal
• The effects of TAS-102 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because topoisomerase inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• \. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

You may not qualify if:

• Patients who have had major surgery within 4 weeks, or chemotherapy or radiotherapy within 2 weeks prior to Cycle 1 Day 1.
• All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to grade 1 or baseline
• Patients may not be receiving any other investigational agents.
• Patients with known brain metastases due to poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102, irinotecan or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Prior treatment with irinotecan or TAS-102
• History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ.
• Inability to comply with study and follow-up procedures as judged by the Investigator
• Patients who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Sponsors & Collaborators

• University of California, Irvine: lead
• Taiho Pharmaceutical Co., Ltd.: collaborator

Study Sites (2)

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Interventions

trifluridine tipiracil drug combination; Trifluridine; tipiracil; Irinotecan

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids

Results Point of Contact

• Title: Chao Family Comprehensive Cancer Center, University of California, Irvine
• Organization: Chao Family Comprehensive Cancer Center, University of California, Irvine

ucstudy@uci.edu

1-877-UC-STUDY

Study Officials

• Farshid Dayyani, MD, PhD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: August 28, 2019
• First Posted: August 30, 2019
• Study Start: August 26, 2019
• Primary Completion: July 14, 2021
• Study Completion: July 21, 2022
• Last Updated: February 2, 2024
• Results First Posted: February 2, 2024

Record last verified: 2023-05

Locations

US (2)