Response Adapted Neoadjuvant Therapy in Gastroesophageal Cancers (RANT-GC Trial)
- Conditions
- Gastroesophageal Adenocarcinoma
- Interventions
- Device: ctDNA Blood TestCombination Product: FLOTCombination Product: FOLFOXCombination Product: FOLFIRICombination Product: FOLFIRINOXCombination Product: PACLITAXEL with or without CARBOPLATINCombination Product: DOCETAXEL and IRINOTECAN (alone or combined)
- 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 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 20
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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.
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Must have Stage IB, II or Stage III GEA eligible for (neo)adjuvant doublet or triplet chemotherapy for up to 6 months.
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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.
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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.
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Performance status: ECOG performance status ≤2
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Life expectancy of greater than 6 months
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Adequate organ and marrow function as defined below:
- leukocytes ≥ 3,000/mcL
- 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
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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.
- 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).
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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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Neoadjuvant chemotherapy with ctDNA testing FOLFIRI The patients will be treated with one of the standard neoadjuvant protocols (FLOT or FOLFOX.) If no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion. Neoadjuvant chemotherapy with ctDNA testing FOLFIRINOX The patients will be treated with one of the standard neoadjuvant protocols (FLOT or FOLFOX.) If no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion. 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 no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion. 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 no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion. Neoadjuvant chemotherapy with ctDNA testing ctDNA Blood Test The patients will be treated with one of the standard neoadjuvant protocols (FLOT or FOLFOX.) If no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion. Neoadjuvant chemotherapy with ctDNA testing FLOT The patients will be treated with one of the standard neoadjuvant protocols (FLOT or FOLFOX.) If no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion. Neoadjuvant chemotherapy with ctDNA testing FOLFOX The patients will be treated with one of the standard neoadjuvant protocols (FLOT or FOLFOX.) If no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion. 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 no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion. 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 no decline in ctDNA detected after 4 cycles, treatment will be switched to a different chemotherapy backbone (e.g. irinotecan based regimen, or taxane based if not used upfront). ctDNA will be re-evaluated after 3 cycles (if a 21 day regimen) or 4 cycles (if a 14 day regimen) of the 2nd line regimen. If ctDNA is lower than the previous measurement, then the same regimen continues for 3-4 more cycles (depending on 14 day or 21 day cycle), followed by gastrectomy. Adjuvant treatment is given based on the investigator's discretion.
- 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 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)
Percentage of patients completing gastrectomy. Up to 3 years Percent of patients completing gastrectomy
Rate of R0 resection Up to 3 years R0 resection is defined as complete tumor removal with negative surgical margins.
Rate of post-operative complication rate within 30 days after surgery Up to 3 years 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
Rate of ctDNA positive patients at diagnosis Up to 3 years Percent of patients positive for ctDNA at diagnosis
Trial Locations
- Locations (1)
Chao Family Comprehensive Cancer Center, University
🇺🇸Orange, California, United States