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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Gastroesophageal Adenocarcinoma
• Intervention / Treatment: Combination product: FLOT; Combination product: FOLFOX; Combination product: FOLFIRI; Combination product: FOLFIRINOX; Combination product: PACLITAXEL with or without CARBOPLATIN; Combination product: DOCETAXEL and IRINOTECAN (alone or combined); Drug: NIVOLUMAB (alone or when added to a regimen above); Drug: PEMBROLIZUMAB (alone or when added to a regimen above); Drug: Durvalumab; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chao Family Comprehensive Cancer Center University of California, Irvine; Phone Number: 1-877-827-8839; Email: ucstudy@uci.edu
• Study Contact Backup: Name: University of California Irvine Medical

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Chao Family Comprehensive Cancer Center, University
      • Contact: Farshid Dayyani, MD, PhD; Phone Number: 877-827-8839; Email: ucstudy@uci.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant chemotherapy with ctDNA testing; The patients will be treated with one of the standard neoadjuvant protocols (FLOT or FOLFOX.) If patient response to their treatment, as measured by CT Scans or MRI results or blood tests done to look tumor markers such as carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9) a change in adjuvant treatment will be made.

Combination product: FLOT; 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 product: FOLFOX; 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 product: FOLFIRI; 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 product: FOLFIRINOX; 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 product: PACLITAXEL 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 product: DOCETAXEL 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; Drug: NIVOLUMAB (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; Drug: PEMBROLIZUMAB (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; Drug: Durvalumab; - 1500 mg IV on Day 1 every 28 days; Drug: Trastuzumab; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of completing per protocol treatment.	Percent of patients who will undergo attempt at curative intent resection.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients completing gastrectomy.	Percent of patients completing gastrectomy	Up to 3 years
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)	8 weeks
Rate of R0 resection	R0 resection is defined as complete tumor removal with negative surgical margins.	Up to 3 years
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.	Up to 3 years
Relapse-free survival time	The lead time in ctDNA detection before clinical recurrence	Up to 3 years

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: BillionToOne, Inc
• Investigators: Principal Investigator: Farshid Dayyani, MD,PhD, Chao Family Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Socioeconomic Factors; Population Characteristics; Demography; Family Characteristics; Marital Status; Docetaxel; Trastuzumab; Nivolumab; Irinotecan; Carboplatin; Paclitaxel; pembrolizumab; durvalumab; Folfox protocol; IFL protocol; folfirinox; Single Person
• Other Study ID Numbers: 1977 (University of California, Irvine); UCI 21-191 (Other Identifier: CFCCC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes