Platform Study of Circulating Tumor DNA Directed Adjuvant Chemotherapy in Colon Cancer (KCSG CO22-12)

NCT05534087 | Recruiting Phase 3 DMC

• 1 other identifier: H-2205-029-1322
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 3

Brief Summary

This study is a prospective, open-label, randomized phase 3 clinical trial. It aims to investigate if the early introduction of intensified chemotherapy (3 months of modified FOLFIRINOX) improves the 3-year disease-free survival rate compared to standard treatment (FOLFOX/CAPOX for an additional three months to complete six months of standard adjuvant chemotherapy) in patients with stage 2-3 colon cancer in whom ctDNA MRD in the part 1 study remained positive during adjuvant FOLFOX/CAPOX chemotherapy

Conditions

Colon Cancer

Keywords

Minimal residual disease; Intensified chemotherapy

Outcome Measures

Primary Outcomes (1)

• 3-year disease-free survival rate

  The rate refers to cases that see first tumor metastasis or recurrence or death of any cause from randomization

  Through completion of follow-up (estimated to be 36 months)

Secondary Outcomes (4)

• Circulating tumor DNA (ctDNA) clearance rate

  The data of ctDNA clearance rate will be collected at 10 time points

• 5-year overall survival rate (5y-OS rate)

  Through completion of follow-up (estimated to be 60 months)

• Treatment-Related Adverse Events

  Through completion of follow-up (estimated to be 36 months)

• EORTC QLQ-C30 scale

  Through completion of follow-up (estimated to be 36 months)

Study Arms (2)

mFOLFIRINOX intensified chemotherapy

EXPERIMENTAL

6 cycles of mFOLFIRINOX \- Modified FOLFIRINOX (mFOLFIRINOX) regimen: 6 cycles every 2 weeks

Drug: mFOLFIRINOX-FOLFIRI intensified chemotherapy

FOLFOX or CAPOX adjuvant chemotherapy

ACTIVE COMPARATOR

FOLFOX 6 cycles or CAPOX 4 cycles * FOLFOX regimen: 6 cycles every 2 weeks or * CAPOX regimen: 4 cycles every 3 weeks

Drug: FOLFOX or CAPOX adjuvant chemotherapy

Interventions

mFOLFIRINOX-FOLFIRI intensified chemotherapy DRUG

(1) Modified FOLFIRINOX (mFOLFIRINOX) regimen: 6 cycles every 2 weeks * Oxaliplatin 85mg/m2 IV infusion over 120 min D1 * Leucovorin 400mg/m2 IV (concurrently with oxaliplatin) * Irinotecan 150mg/m2 IV infusion over 60-90 min D1 * 5-fluorouracil 2,400mg/m2 IV infusion continuously over 46-48h D1-2

mFOLFIRINOX intensified chemotherapy

FOLFOX or CAPOX adjuvant chemotherapy DRUG

1. FOLFOX regimen: 6 cycles every 2 weeks * Oxaliplatin 85mg/m2 IV infusion over 120 min D1 * Leucovorin 400mg/m2 IV infusion over 120 min (concurrently with oxaliplatin) * 5-fluorouracil 400mg/m2 IV bolus D1 * 5-fluorouracil 2,400mg/m2 IV infusion continuously over 46-48h D1-2 or 2. CAPOX regimen: 4 cycles every 3 weeks * Oxaliplatin 130mg/m2 IV infusion over 120 min D1 * Capecitabine 1,000mg/m2 PO bid D1-14

FOLFOX or CAPOX adjuvant chemotherapy

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who willingly consented and signed the informed consent form to participate in the study
• Age range of 19 to 75 years
• Adenocarcinoma of colon confirmed by histology
• Patients with stage II-III colon cancer as defined by the American Joint Committee on Cancer's eighth edition (Stage II cancer is limited to patients who are at a high risk, with more than one risk factor for recurrence.)
• Patients who have completed the sixth cycle of FOLFOX or the fourth cycle of CAPOX adjuvant chemotherapy for colon cancer following radical resection (R0 resection)
• A ctDNA test performed 3 to 6 weeks after surgery reveals a positive MRD
• ECOG performance scale of 0-1 (only 1 is allowed for 70-75 years old)
• Adequate bone marrow function \[ANC ≥1,300/LL, platelets ≥75,000/LL, hemoglobin ≥8.0g/dL (may be eligible in study if intermittent transfusion is required)\]
• Appropriate liver function (total bilirubin ≤1.5xULN, AST and ALT ≤3xULN)
• Appropriate renal function (serum creatine ≤1.5xULN, renal clearance rate ≥50 ml/min)
• Patients who are deemed to understand the study protocol and are willing to participate in the trial until it is completed

You may not qualify if:

• Pregnant or lactating women
• Pregnant women who had a positive pregnancy test at the time of the baseline examination (postmenopausal women must be amenable for at least 12 months to be considered non-fertility)
• Sexually active men and women of reproductive age who are unwilling to use contraception throughout the study treatment and for a period of 6 months (female) or 3 months (male) following the discontinuation of study treatment
• Clinically significant heart condition \[unstable angina requiring medication, symptomatic coronary artery disease, congestive heart failure, or significant heart arrhythmia above NYHA II, or acute coronary syndrome, including myocardial infarction within the last 6 months\]
• Active viral infections such as HIV (However, HBV carriers may enroll if their HBV DNA titer is less than 20,000 IU/ml, and antiviral drugs for hepatitis B may be administered prophylactically at the investigator's discretion)
• Significant uncontrolled infections or other uncontrolled comorbidities
• Symptomatic inflammatory bowel disease
• Allogeneic transplantation history necessitating immunosuppressive therapy
• A history of other malignancies identified within the last three years, except for completed removed basal cell carcinoma of the skin, completely removed cervical epithelial carcinoma, and thyroid cancer that has been treated, including surgery
• Recurrent or residual disease identified clinically or radiographically
• Previous history of irinotecan treatment
• Polyposis including familial adenomatous polyps
• Two or more colon or rectal cancers with a pathologic stage greater than II that were detected concurrently or within the last three years
• When the investigator determines that the subjects' safety may be jeopardized during the study because of other serious or unstable pre-existing medical or mental conditions
• Prior clinical trial participation and usage of investigational drugs or devices following radical resection of colon cancer

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (3)

National Cancer Center

Goyang, South Korea

RECRUITING

Jin Won Kim

Seongnam, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms; Neoplasm, Residual

Interventions

Folfox protocol

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sae-Won Han, MD,PhD

  Seoul National University Hospital South Korea

  PRINCIPAL INVESTIGATOR

• Youngjun Cha, MD

  Natioal Cancer Center South Korea

  STUDY DIRECTOR

Central Study Contacts

Sae-Won Han, MD,PhD

CONTACT

82-2-2072-0795; saewon1@snu.ac.kr

Youngjun Cha, MD

CONTACT

82-2-2072-0795; yongjuncha@ncc.re.kr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 9, 2022
• Study Start: December 15, 2022
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2030
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3)