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

University of California Irvine (UCI)

Status and phase

Enrolling

Phase 1

Conditions

Gastroesophageal Adenocarcinoma

Treatments

Drug: NIVOLUMAB (alone or when added to a regimen above)

Combination Product: FOLFIRINOX

Combination Product: PACLITAXEL with or without CARBOPLATIN

Drug: Trastuzumab

Combination Product: FLOT

Combination Product: DOCETAXEL and IRINOTECAN (alone or combined)

Drug: Durvalumab

Combination Product: FOLFIRI

Combination Product: FOLFOX

Drug: PEMBROLIZUMAB (alone or when added to a regimen above)

Study type

Interventional

Funder types

Other

Identifiers

NCT05733689

UCI 21-191 (Other Identifier)

1977

Details and patient eligibility

About

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).

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

20 participants in 1 patient group

Neoadjuvant chemotherapy with ctDNA testing

Experimental group

Description:

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.

Treatment: