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
- Patients must have histologically or cytologically confirmed gastric or
- Must have locally advanced, recurrent, or metastatic disease not amenable to curative
- 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
- 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
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.
- 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
- 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
- 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.