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

NCT ID: NCT05534087

Last Updated: 2024-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

236 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-15

Study Completion Date

2030-09-30

Brief Summary

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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

Detailed Description

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About 25% of resectable high-risk stage 2 or stage 3 colon cancers are known to relapse despite standard treatments, including radical resection and adjuvant chemotherapy.

Using circulating tumor DNA (ctDNA)-based minimal residual cancer (MRD) detection technology, patients whose MRD is not eradicated after adjuvant chemotherapy could be identified. Early introduction of intensified chemotherapy for this group of patients could prolong survival time and increase cure rates.

This study is part of the Platform Study of Circulating Tumor DNA Directed Adjuvant Chemotherapy in Colon Cancer (CLADIA Colon Cancer). Part 1 of the platform study (Prospective Observational Study of ctDNA Monitoring During Adjuvant) is a large-scale, prospective observational study that follows ctDNA up to three years after resection in about 1,200 patients with stage 2-3 colon cancer.

This study (Part 2) aims to study the efficacy of early intensified chemotherapy (3 months of modified FOLFIRINOX ) 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

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Colon Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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mFOLFIRINOX intensified chemotherapy

6 cycles of mFOLFIRINOX

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

Group Type EXPERIMENTAL

mFOLFIRINOX-FOLFIRI intensified chemotherapy

Intervention Type 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

FOLFOX or CAPOX adjuvant chemotherapy

FOLFOX 6 cycles or CAPOX 4 cycles

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

Group Type ACTIVE_COMPARATOR

FOLFOX or CAPOX adjuvant chemotherapy

Intervention Type 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

Interventions

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mFOLFIRINOX-FOLFIRI intensified chemotherapy

(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

Intervention Type DRUG

FOLFOX or CAPOX adjuvant chemotherapy

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients who willingly consented and signed the informed consent form to participate in the study
2. Age range of 19 to 75 years
3. Adenocarcinoma of colon confirmed by histology
4. 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.)
5. 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)
6. A ctDNA test performed 3 to 6 weeks after surgery reveals a positive MRD
7. ECOG performance scale of 0-1 (only 1 is allowed for 70-75 years old)
8. Adequate bone marrow function \[ANC ≥1,300/LL, platelets ≥75,000/LL, hemoglobin ≥8.0g/dL (may be eligible in study if intermittent transfusion is required)\]
9. Appropriate liver function (total bilirubin ≤1.5xULN, AST and ALT ≤3xULN)
10. Appropriate renal function (serum creatine ≤1.5xULN, renal clearance rate ≥50 ml/min)
11. Patients who are deemed to understand the study protocol and are willing to participate in the trial until it is completed

Exclusion Criteria

1. Pregnant or lactating women
2. 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)
3. 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
4. Clinically significant heart condition \[unstable angina requiring medication, symptomatic coronary artery disease, congestive heart failure, or significant heart arrhythmia above NYHA II, or acute coronary syndrome, including myocardial infarction within the last 6 months\]
5. 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)
6. Significant uncontrolled infections or other uncontrolled comorbidities
7. Symptomatic inflammatory bowel disease
8. Allogeneic transplantation history necessitating immunosuppressive therapy
9. 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
10. Recurrent or residual disease identified clinically or radiographically
11. Previous history of irinotecan treatment
12. Polyposis including familial adenomatous polyps
13. Two or more colon or rectal cancers with a pathologic stage greater than II that were detected concurrently or within the last three years
14. 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
15. Prior clinical trial participation and usage of investigational drugs or devices following radical resection of colon cancer
16. Patients with peripheral neuropathy who have a CTCAE v5 grade 3 or higher functional disability (corresponds to "severe symptoms, limiting self-care activity of daily living" according to CTCAE v5 criteria)
17. Previous anaphylactic reaction or severe and unexpected reactions to fluoropyrimidines or platinum
18. Gilbert's syndrome, dehydro-pyridine dehydrogenase (DPD) deficiency, or homozygous UGT1A1\*28 alleles
Minimum Eligible Age

19 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Seoul National University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Sae-Won Han

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sae-Won Han, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital South Korea

Youngjun Cha, MD

Role: STUDY_DIRECTOR

Natioal Cancer Center South Korea

Locations

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National Cancer Center

Goyang, , South Korea

Site Status RECRUITING

Jin Won Kim

Seongnam, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Sae-Won Han, MD,PhD

Role: CONTACT

82-2-2072-0795

Youngjun Cha, MD

Role: CONTACT

82-2-2072-0795

Facility Contacts

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Yongjun Cha

Role: primary

Jin Won Kim

Role: primary

Sae-Won Han

Role: primary

Other Identifiers

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H-2205-029-1322

Identifier Type: -

Identifier Source: org_study_id