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

Gastroesophageal Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05733689
• Other study ID #: 1977
• Secondary ID: UCI 21-191
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: February 2025
• Est. completion date: February 2026

Study information

• Verified date: February 2024
• Source: University of California, Irvine
• Contact: Chao Family Comprehensive Cancer Center University of California
• Phone: 1-877-827-8839
• Email: ucstudy[@]uci.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1b prospective, single arm, open-label trial determining the efficacy and feasibility of using a ctDNA assay (test) result to help guide neoadjuvant chemotherapy in subjects with Stage IB, II or Stage III adenocarcinoma of the stomach or gastroesophageal junction (GEA).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.
• Must have baseline ctDNA positive assay (tested by Signatera MRD assay) prior to initiation of neoadjuvant chemotherapy. Patients who are otherwise eligible may start per protocol treatment if ctDNA result is not available at the time of initiation of systemic therapy. However, once the results is available, they can only remain on study if the ctDNA is positive.
• 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. leukocytes = 3,000/mcL

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 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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastroesophageal Adenocarcinoma

Intervention

Device:
• ctDNA Blood Test
Blood will be collected for ctDNA testing

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
• 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
• 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
• 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
• 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
• 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
• 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

Locations

Country	Name	City	State
United States	Chao Family Comprehensive Cancer Center, University	Orange	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Irvine	Natera, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of completing per protocol treatment.	Percent of patients who will undergo attempt at curative intent resection.	Up to 3 years
Secondary	Percentage of patients completing gastrectomy.	Percent of patients completing gastrectomy	Up to 3 years
Secondary	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
Secondary	Rate of R0 resection	R0 resection is defined as complete tumor removal with negative surgical margins.	Up to 3 years
Secondary	Rate of post-operative complication rate within 30 days after surgery		Up to 3 years
Secondary	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
Secondary	Relapse-free survival time	The lead time in ctDNA detection before clinical recurrence	Up to 3 years
Secondary	Rate of ctDNA positive patients at diagnosis	Percent of patients positive for ctDNA at diagnosis	Up to 3 years