Response Adapted Neoadjuvant Therapy in Gastroesophageal Cancers (RANT-GC Trial)

Inclusion Criteria: Patients must have histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (GEA). Other GE histologies which are treated per NCCN guidelines for neoadjuvant treatment are eligible. Must have Stage IB, II or Stage III GEA eligible for (neo)adjuvant doublet or triplet chemotherapy for up to 6 months. Must have baseline ctDNA positive assay (tested by Signatera MRD assay) prior to initiation of neoadjuvant chemotherapy. Patients who are otherwise eligible may start per protocol treatment if ctDNA result is not available at the time of initiation of systemic therapy. However, once the results is available, they can only remain on study if the ctDNA is positive. Age ≥ 18 years Because the safety or efficacy of neoadjuvant chemotherapy for LGEA has not been tested or established for patients <18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable. Performance status: ECOG performance status ≤2 Life expectancy of greater than 6 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) ≤ 5 X institutional upper limit of normal creatinine <2 X ULN Docetaxel can cause fetal harm and irinotecan is known to be teratogenic. Since these compounds are part of the treatment regimens, 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 understand and the willingness to sign a written informed consent. 1. Both men and women and members of all races and ethnic groups are eligible for this trial. Non-English speaking, deaf, hard of hearing and illiterate individuals are eligible for this trial. Exclusion Criteria: Patients may not be receiving any other investigational agents. Patients with known metastases from GEA. History of allergic reactions attributed to 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. History of another primary cancer which requires active treatment or is expected to require treatment within 12 months after enrollment. 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.