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

NCT05733689 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 1977UCI 21-191
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Gastroesophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of completing per protocol treatment.

  Percent of patients who will undergo attempt at curative intent resection.

  Up to 3 years

Secondary Outcomes (5)

• Percentage of patients completing gastrectomy.

  Up to 3 years

• Rate of negative ctDNA after completion of neoadjuvant treatment and within 8 weeks after surgery

  8 weeks

• Rate of R0 resection

  Up to 3 years

• Percentage of Grade 3-5 Adverse Events

  Up to 3 years

• Relapse-free survival time

  Up to 3 years

Study Arms (1)

Neoadjuvant chemotherapy with ctDNA testing

EXPERIMENTAL

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; 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

Interventions

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

Neoadjuvant chemotherapy with ctDNA testing

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

Neoadjuvant chemotherapy with ctDNA testing

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

Neoadjuvant chemotherapy with ctDNA testing

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

Neoadjuvant chemotherapy with ctDNA testing

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

Neoadjuvant chemotherapy with ctDNA testing

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

Neoadjuvant chemotherapy with ctDNA testing

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

Neoadjuvant chemotherapy with ctDNA testing

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

Neoadjuvant chemotherapy with ctDNA testing

Durvalumab DRUG

\- 1500 mg IV on Day 1 every 28 days

Neoadjuvant chemotherapy with ctDNA testing

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

Neoadjuvant chemotherapy with ctDNA testing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• hemoglobin ≥ 7g/dL
• 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.
• \. 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Irvine: lead
• BillionToOne, Inc: collaborator

Study Sites (1)

Chao Family Comprehensive Cancer Center, University

Orange, California, 92868, United States

RECRUITING

MeSH Terms

Interventions

Folfox protocol; IFL protocol; folfirinox; Paclitaxel; Carboplatin; Docetaxel; Irinotecan; Single Person; Nivolumab; pembrolizumab; durvalumab; Trastuzumab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Camptothecin; Alkaloids; Heterocyclic Compounds; Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Farshid Dayyani, MD,PhD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao Family Comprehensive Cancer Center University of California, Irvine

CONTACT

1-877-827-8839; ucstudy@uci.edu

University of California Irvine Medical

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Medicine

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: February 17, 2023
• Study Start: June 27, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

US (1)