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).
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
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.
Single group
FLOT
Combination product* 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
FOLFOX
Combination product* 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
FOLFIRI
Combination product* 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
FOLFIRINOX
Combination product* 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
PACLITAXEL with or without CARBOPLATIN
Combination product* 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
DOCETAXEL and IRINOTECAN (alone or combined)
Combination product* 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
NIVOLUMAB (alone or when added to a regimen above)
Drug* 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
PEMBROLIZUMAB (alone or when added to a regimen above)
Drug* 200 mg IV on Day 1 every 21 days, or * 400 mg IV on Day 1 every 42 days
Durvalumab
Drug\- 1500 mg IV on Day 1 every 28 days
Trastuzumab
Drug* 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
Percentage of completing per protocol treatment.
Percent of patients who will undergo attempt at curative intent resection.
Percentage of patients completing gastrectomy.
Percent of patients completing gastrectomy
Rate of negative ctDNA after completion of neoadjuvant treatment and within 8 weeks after surgery
Percent of patients with ctDNA clearance after neoadjuvant chemotherapy and after surgery (within 6-8 weeks)
Rate of R0 resection
R0 resection is defined as complete tumor removal with negative surgical margins.
Percentage of Grade 3-5 Adverse Events
Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.
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University of California, Irvine
Lead sponsor
BillionToOne Inc.
Collaborator
