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

NCT ID: NCT05733689

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-27
• Study Completion Date: 2026-02-28

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

FLOT

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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)

Intervention Type: 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)

Intervention Type: 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)

Intervention Type: DRUG

• 200 mg IV on Day 1 every 21 days, or
• 400 mg IV on Day 1 every 42 days

Durvalumab

Intervention Type: DRUG

\- 1500 mg IV on Day 1 every 28 days

Trastuzumab

Intervention Type: 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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: COMBINATION_PRODUCT

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

Intervention Type: 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

Intervention Type: DRUG

Durvalumab

\- 1500 mg IV on Day 1 every 28 days

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BillionToOne, Inc

UNKNOWN

Sponsor Role: collaborator

University of California, Irvine

OTHER

Sponsor Role: lead

Responsible Party

Farshid Dayyani

Professor of Clinical Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Farshid Dayyani, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Chao Family Comprehensive Cancer Center

Locations

Chao Family Comprehensive Cancer Center, University

Orange, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Chao Family Comprehensive Cancer Center University of California, Irvine

Role: CONTACT

ucstudy@uci.edu

1-877-827-8839

University of California Irvine Medical

Role: CONTACT

Facility Contacts

Farshid Dayyani, MD, PhD

Role: primary

ucstudy@uci.edu

877-827-8839

Other Identifiers

UCI 21-191

Identifier Type: OTHER

Identifier Source: secondary_id

1977

Identifier Type: -

Identifier Source: org_study_id