Clinical trial NCT05733689: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Gastroesophageal Adenocarcinoma
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: Natera, Inc.
First posted: 2023-02-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


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.
* 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.

Primary outcomes:
measure: Percentage of completing per protocol treatment.
timeFrame: Up to 3 years
Secondary outcomes:
measure: Percentage of patients completing gastrectomy.
timeFrame: Up to 3 years
measure: Rate of negative ctDNA after completion of neoadjuvant treatment and within 8 weeks after surgery
timeFrame: 8 weeks
measure: Rate of R0 resection
timeFrame: Up to 3 years
measure: Rate of post-operative complication rate within 30 days after surgery
timeFrame: Up to 3 years
measure: Percentage of Grade 3-5 Adverse Events
timeFrame: Up to 3 years
measure: Relapse-free survival time
timeFrame: Up to 3 years
measure: Rate of ctDNA positive patients at diagnosis
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center, University
state: California
Study officials:
affiliation: Chao Family Comprehensive Cancer Center
name: Farshid Dayyani, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: