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

Primary Purpose

Gastroesophageal Adenocarcinoma

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ctDNA Blood Test
FLOT
FOLFOX
FOLFIRI
FOLFIRINOX
PACLITAXEL with or without CARBOPLATIN
DOCETAXEL and IRINOTECAN (alone or combined)
NIVOLUMAB (alone or when added to a regimen above)
PEMBROLIZUMAB (alone or when added to a regimen above)
Sponsored by
University of California, Irvine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastroesophageal Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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. 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: 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 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 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.

Sites / Locations

  • Chao Family Comprehensive Cancer Center, University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant chemotherapy with ctDNA testing

Arm Description

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.

Outcomes

Primary Outcome Measures

Percentage of completing per protocol treatment.
Percent of patients who will undergo attempt at curative intent resection.

Secondary Outcome Measures

Percentage of patients completing gastrectomy.
Percent of patients completing gastrectomy
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)
Rate of R0 resection
R0 resection is defined as complete tumor removal with negative surgical margins.
Rate of post-operative complication rate within 30 days after surgery
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.
Relapse-free survival time
The lead time in ctDNA detection before clinical recurrence
Rate of ctDNA positive patients at diagnosis
Percent of patients positive for ctDNA at diagnosis

Full Information

First Posted
February 8, 2023
Last Updated
June 2, 2023
Sponsor
University of California, Irvine
Collaborators
Natera, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05733689
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2023 (Anticipated)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
February 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Irvine
Collaborators
Natera, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroesophageal Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant chemotherapy with ctDNA testing
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
ctDNA Blood Test
Intervention Description
Blood will be collected for ctDNA testing
Intervention Type
Combination Product
Intervention Name(s)
FLOT
Intervention Description
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
Intervention Type
Combination Product
Intervention Name(s)
FOLFOX
Intervention Description
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
Intervention Type
Combination Product
Intervention Name(s)
FOLFIRI
Intervention Description
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
Intervention Type
Combination Product
Intervention Name(s)
FOLFIRINOX
Intervention Description
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
Intervention Type
Combination Product
Intervention Name(s)
PACLITAXEL with or without CARBOPLATIN
Intervention Description
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
Intervention Type
Combination Product
Intervention Name(s)
DOCETAXEL and IRINOTECAN (alone or combined)
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
NIVOLUMAB (alone or when added to a regimen above)
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
PEMBROLIZUMAB (alone or when added to a regimen above)
Intervention Description
200 mg IV on Day 1 every 21 days, or 400 mg IV on Day 1 every 42 days
Primary Outcome Measure Information:
Title
Percentage of completing per protocol treatment.
Description
Percent of patients who will undergo attempt at curative intent resection.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Percentage of patients completing gastrectomy.
Description
Percent of patients completing gastrectomy
Time Frame
Up to 3 years
Title
Rate of negative ctDNA after completion of neoadjuvant treatment and within 8 weeks after surgery
Description
Percent of patients with ctDNA clearance after neoadjuvant chemotherapy and after surgery (within 6-8 weeks)
Time Frame
8 weeks
Title
Rate of R0 resection
Description
R0 resection is defined as complete tumor removal with negative surgical margins.
Time Frame
Up to 3 years
Title
Rate of post-operative complication rate within 30 days after surgery
Time Frame
Up to 3 years
Title
Percentage of Grade 3-5 Adverse Events
Description
Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.
Time Frame
Up to 3 years
Title
Relapse-free survival time
Description
The lead time in ctDNA detection before clinical recurrence
Time Frame
Up to 3 years
Title
Rate of ctDNA positive patients at diagnosis
Description
Percent of patients positive for ctDNA at diagnosis
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chao Family Comprehensive Cancer Center University of California, Irvine
Phone
1-877-827-8839
Email
ucstudy@uci.edu
First Name & Middle Initial & Last Name or Official Title & Degree
University of California Irvine Medical
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Farshid Dayyani, MD,PhD
Organizational Affiliation
Chao Family Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chao Family Comprehensive Cancer Center, University
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farshid Dayyani, MD, PhD
Phone
877-827-8839
Email
ucstudy@uci.edu

12. IPD Sharing Statement

Learn more about this trial

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

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