Clinical Trials /

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

NCT04074343

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TAS-102 and Irinotecan in 2L+ Gastric and Gastroesophageal Adenocarcinoma
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: UCI 18-125
  • SECONDARY ID: 2019-5179
  • NCT ID: NCT04074343

Conditions

  • Gastric Adenocarcinoma
  • GastroEsophageal Cancer

Interventions

DrugSynonymsArms
TAS-102LONSURF, trifluoridine and tipiracilTAS-102 and Irinotecan
IrinotecanCAMPTOSAR, CPT-11TAS-102 and Irinotecan

Purpose

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

      Treatment on study will be administered in 14 day cycles.
    

Trial Arms

NameTypeDescriptionInterventions
TAS-102 and IrinotecanExperimentalPatients 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.
  • TAS-102
  • Irinotecan

Eligibility Criteria

        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:

               1. leukocytes : ≥ 3,000/mcL

               2. absolute neutrophil count: ≥ 1,500/mcL

               3. platelets: ≥ 80,000/mcl

               4. total bilirubin: within normal institutional limits

               5. AST(SGOT)/ALT(SPGT): ≤ 3 X institutional upper limit of normal or ≤ 5 X if liver
                  metastases are present

               6. creatinine: within normal institutional limits

          -  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:

               1. Has not undergone a hysterectomy or bilateral oophorectomy; or

               2. 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 entering the study

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Progression-free Survival at 6 Months
Time Frame:6 Months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Percentage of Grade 3-5 Adverse Events
Time Frame:8 Weeks
Safety Issue:
Description: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.
Measure:Overall Response Rate as Assessed by RECIST v1.1 Criteria of Patients Who Received TAS-102 and Irinotecan
Time Frame: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.
Safety Issue:
Description: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
Measure:Overall Survival of Patients Who Received TAS-102 and Irinotecan
Time Frame:From date of registration for up to 18 months after last patient is enrolled or until death from any cause, whichever came first.
Safety Issue:
Description:To evaluate overall survival in patients with advanced recurrent or unresectable and gastroesophageal adenocarcinoma treated with this combination of TAS-102 and Irinotecan.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, Irvine

Trial Keywords

  • Gastric Adenocarcinoma
  • TAS-102
  • Irinotecan
  • Gastroesophageal Adenocarcinoma

Last Updated

May 26, 2020