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

Phase 1

Recruiting

• Conditions: Gastroesophageal Adenocarcinoma
• Interventions: 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

• Registration Number: NCT05733689
• Lead Sponsor: University of California, Irvine

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-08
• Study First Submitted QC: 2023-02-08
• Study First Posted: 2023-02-17
• Study Start: 2025-06-27
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-02
• Last Update Posted: 2025-07-08
• Primary Completion: 2026-02
• Study Completion: 2026-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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:
  2. Has not undergone a hysterectomy or bilateral oophorectomy; or
  3. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant chemotherapy with ctDNA testing	FLOT	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.
Neoadjuvant chemotherapy with ctDNA testing	FOLFOX	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.
Neoadjuvant chemotherapy with ctDNA testing	FOLFIRI	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.
Neoadjuvant chemotherapy with ctDNA testing	FOLFIRINOX	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.
Neoadjuvant chemotherapy with ctDNA testing	PACLITAXEL with or without CARBOPLATIN	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.
Neoadjuvant chemotherapy with ctDNA testing	DOCETAXEL and IRINOTECAN (alone or combined)	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.
Neoadjuvant chemotherapy with ctDNA testing	NIVOLUMAB (alone or when added to a regimen above)	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.
Neoadjuvant chemotherapy with ctDNA testing	PEMBROLIZUMAB (alone or when added to a regimen above)	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.
Neoadjuvant chemotherapy with ctDNA testing	Durvalumab	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.
Neoadjuvant chemotherapy with ctDNA testing	Trastuzumab	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Percentage of patients completing gastrectomy.	Up to 3 years	Percent of patients completing gastrectomy
Rate of negative ctDNA after completion of neoadjuvant treatment and within 8 weeks after surgery	8 weeks	Percent of patients with ctDNA clearance after neoadjuvant chemotherapy and after surgery (within 6-8 weeks)
Rate of R0 resection	Up to 3 years	R0 resection is defined as complete tumor removal with negative surgical margins.
Percentage of Grade 3-5 Adverse Events	Up to 3 years	Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.
Relapse-free survival time	Up to 3 years	The lead time in ctDNA detection before clinical recurrence

Trial Locations

Locations (1)

Chao Family Comprehensive Cancer Center, University; 🇺🇸 Orange, California, United States