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

Official title

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

Overview

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).

Interventions

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Drug Durvalumab
  \- 1500 mg IV on Day 1 every 28 days
• 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

Primary outcome measures

• Percentage of completing per protocol treatment. [Time frame: Up to 3 years]

Secondary outcome measures (5)

• Percentage of patients completing gastrectomy. [Time frame: Up to 3 years]
• Rate of negative ctDNA after completion of neoadjuvant treatment and within 8 weeks after surgery [Time frame: 8 weeks]
• Rate of R0 resection [Time frame: Up to 3 years]
• Percentage of Grade 3-5 Adverse Events [Time frame: Up to 3 years]
• Relapse-free survival time [Time frame: Up to 3 years]

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:

• 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.

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:

• Has not undergone a hysterectomy or bilateral oophorectomy; or
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Chao Family Comprehensive Cancer Center, University — Orange

Identifiers

NCT: NCT05733689 · 1977 · UCI 21-191

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗