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

Study Overview
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Brief Summary
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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.

Detailed Description
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Treatment on study will be administered in 14 day cycles.

Official Title
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A Phase Ib Multicenter Study of TAS-102 in Combination With Irinotecan in Patients With Advanced Recurrent or Unresectable Gastric and Gastroesophageal Adenocarcinoma After at Least One Line of Treatment With a Fluoropyrimidine and Platinum Containing Regimen

Conditions
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Gastric Adenocarcinoma, GastroEsophageal Cancer

Intervention / Treatment
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* Drug: TAS-102
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 1. 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: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Ability to swallow tablets Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS-102 and Irinotecan<br>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<br>* Given PO<br>* Other names: trifluoridine and tipiracil;Drug: Irinotecan<br>* Given IV<br>* Other names: CPT-11;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Grade 3-5 Adverse Events | To evaluate the tolerability of administering TAS-102 in combination with Irinotecan in patients with advanced recurrent or unresectable gastric and gastroesophageal adenocarcinoma for the first 2 cycles of study treatment. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0. | 8 Weeks | 
| Overall Response Rate as Assessed by RECIST v1.1 Criteria of Patients Who Received TAS-102 and Irinotecan | To assess the overall response rate to the combination of TAS-102 and Irinotecan. Overall response rate (ORR) is defined as confirmed complete response (CR) and partial response (PR). Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR | 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 Who Received TAS-102 and Irinotecan | To evaluate overall survival in patients with advanced recurrent or unresectable and gastroesophageal adenocarcinoma treated with this combination of 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TAS-102, Gastric Adenocarcinoma, Irinotecan, Gastroesophageal Adenocarcinoma