RecruitingInterventionalPhase 1

Response Adapted Neoadjuvant Therapy in Gastroesophageal Cancers (RANT-GC Trial) - a Phase Ib Feasibility Trial

NCT ID: NCT05733689Sponsor: University of California, IrvineLast updated: 2026-03-10

Summary

This is a phase 1b prospective, single arm, open-label trial determining the efficacy and feasibility of using a response-guided approach to help guide neoadjuvant chemotherapy in subjects with Stage IB, II or Stage III adenocarcinoma of the stomach or gastroesophageal junction (GEA).

Arms & interventions

Combination ProductFLOT
* Oxaliplatin 85 mg/m2 IV on Day 1 * Docetaxel 50 mg/m2 IV on Day 1 * Leucovorin 200 mg/m2 IV on Day 1 * Fluorouracil 2600 mg/m2 continuous infusion over 24 hours daily on Day 1 Every 14 Days
Combination ProductFOLFOX
* Oxaliplatin 85 mg/m2 IV on Day 1 * Leucovorin 400 mg/m2 IV on Day 1 * Fluorouracil 400 mg/m2 IV Push on Day 1 * Fluorouracil 1200 mg/m2 continuous infusion over 24 hours daily on Days 1 and 2 Every 14 Days
Combination ProductFOLFIRI
* Irinotecan 180 mg/m2 IV on Day 1 * Leucovorin 400 mg/m2 IV on Day 1 * Fluorouracil 400 mg/m2 IV Push on Day 1 * Fluorouracil 1200 mg/m2 continuous infusion over 24 hours daily on Days 1 and 2 Every 14 Days
Combination ProductFOLFIRINOX
* Oxaliplatin 85 mg/m2 IV on Day 1 * Irinotecan 150 mg/m2 IV on Day 1 * Leucovorin 200 mg/m2 IV on Day 1 * Fluorouracil 1200 mg/m2 continuous infusion over 24 hours daily on Days 1 and 2 Every 14 days
Combination ProductPACLITAXEL with or without CARBOPLATIN
* Paclitaxel 200 mg/m2 IV on Day 1 * Carboplatin AUC 5 IV on day 1 Every 21 Days OR \- Paclitaxel 80mg/m2 IV on Days 1,8,15 Every 28 Days
Combination ProductDOCETAXEL and IRINOTECAN (alone or combined)
* Docetaxel 35 mg/m2 IV on Days 1 and 8 * Irinotecan 50 mg/m2 IV on Days 1 and 8 Every 21 Days * Docetaxel 75 mg/m2 IV on Day 1 Every 21 Days * Docetaxel 150 mg/m2 IV on Day 1 Every 14 Days
DrugNIVOLUMAB (alone or when added to a regimen above)
* 240 mg IV on Day 1 every 14 days, or * 360 mg IV on Day 1 every 21 days, or * 480 mg IV on Day 1 every 28 days
DrugPEMBROLIZUMAB (alone or when added to a regimen above)
* 200 mg IV on Day 1 every 21 days, or * 400 mg IV on Day 1 every 42 days
DrugDurvalumab
\- 1500 mg IV on Day 1 every 28 days
DrugTrastuzumab
* 8 mg/kg on Day 1, then 6 mg/kg IV every 21 days, or * 6 mg/kg on Day 1, then 4 mg/kg IV every 14 days

Outcome measures

Primary

Percentage of completing per protocol treatment.
Percent of patients who will undergo attempt at curative intent resection.
Time frame: Up to 3 years

Secondary

Percentage of patients completing gastrectomy.
Time frame: Up to 3 years
Rate of negative ctDNA after completion of neoadjuvant treatment and within 8 weeks after surgery
Time frame: 8 weeks
Rate of R0 resection
Time frame: Up to 3 years
Percentage of Grade 3-5 Adverse Events
Time frame: Up to 3 years
Relapse-free survival time
Time frame: Up to 3 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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. * 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: 1. hemoglobin ≥ 7g/dL 2. absolute neutrophil count ≥ 1,500/mcL 3. platelets ≥ 80,000/mcl 4. total bilirubin within normal institutional limits 5. AST(SGOT)/ALT(SPGT) ≤ 5 X institutional upper limit of normal 6. 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: 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 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 distant 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. * Patients with prior organ/bone marrow/non-autologous stem cell transplants

Study locations (1)

Chao Family Comprehensive Cancer Center, University

Orange, California, 92868

Recruiting

Farshid Dayyani, MD, PhD · Contact

877-827-8839 ucstudy@uci.edu