CLAUDIA: Platform Study of Circulating Tumor DNA Directed Adjuvant Chemotherapy in Colon Cancer

• Sponsor: Seoul National University Hospital (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05534087
• Collaborator: (none)
• Enrollment: 228
• Arms: 2
• Anticipated Duration (Months): 96

Study Details

Study Description

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 followed by three months of FOLFIRI) 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

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer	Drug: mFOLFIRINOX-FOLFIRI intensified chemotherapy; Drug: FOLFOX or CAPOX adjuvant chemotherapy	Phase 3

Detailed Description

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 followed by three months of FOLFIRI) 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 228 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Phase III Trial of Treatment Intensification in Stage II-III Colon Cancer Patients With Positive MRD During Adjuvant Chemotherapy
• Anticipated Study Start Date: Oct 1, 2022
• Anticipated Primary Completion Date: Sep 30, 2028
• Anticipated Study Completion Date: Sep 30, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mFOLFIRINOX-FOLFIRI intensified chemotherapy 6 cycles of mFOLFIRINOX followed by 6 cycles of FOLFIRI Modified FOLFIRINOX (mFOLFIRINOX) regimen: 6 cycles every 2 weeks FOLFIRI regimen: 6 cycles every 2 weeks	Drug: mFOLFIRINOX-FOLFIRI intensified chemotherapy; 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 FOLFIRI regimen: 6 cycles every 2 weeks Irinotecan 150mg/m2 IV infusion over 30-90 min D1 Leucovorin 400mg/m2 IV infusion over 30-90 min (concurrently with irinotecan) 5-fluorouracil 2,400mg/m2 IV infusion continuously over 46-48h D1
Active Comparator: 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	Drug: FOLFOX or CAPOX adjuvant chemotherapy; 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 CAPOX regimen: 4 cycles every 3 weeks Oxaliplatin 130mg/m2 IV infusion over 120 min D1 Capecitabine 1,000mg/m2 PO bid D1-14

Outcome Measures

Primary Outcome Measures

1. 3-year disease-free survival rate [Through completion of follow-up (estimated to be 36 months)]

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

Secondary Outcome Measures

1. Circulating tumor DNA (ctDNA) clearance rate [The data of ctDNA clearance rate will be collected at 10 time points]

   The proportion of patients with circulating tumor DNA clearance after 36months study treatment.

2. 5-year overall survival rate (5y-OS rate) [Through completion of follow-up (estimated to be 60 months)]

   Overall survival is defined as the time from beginning of study treatment until death due to any cause.

3. Treatment-Related Adverse Events [Through completion of follow-up (estimated to be 36 months)]

   The number of patients with adverse events and the severity according to CTCAE v5.0.

4. EORTC QLQ-C30 scale [Through completion of follow-up (estimated to be 36 months)]

   Using the EORTC QLQ-C30 scale (European Organization for Research on Treatment of Cancer Quality of Life Questionnaire-Core 30) to evaluate the quality of life of patients.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 three months following surgery (P3) reveals a positive MRD

7. At least four cycles of FOLFOX or three cycles of CAPOX prior to P3 ctDNA testing

8. ECOG performance scale of 0-1 (only 1 is allowed for 70-75 years old)

9. 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)]

10. Appropriate liver function (total bilirubin ≤1.5xULN, AST and ALT ≤3xULN)

11. Appropriate renal function (serum creatine ≤1.5xULN, renal clearance rate ≥50 ml/min)

12. 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)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Seoul National University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sae-Won Han, Professor, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT05534087
• Other Study ID Numbers: H-2205-029-1322
• First Posted: Sep 9, 2022
• Last Update Posted: Sep 9, 2022
• Last Verified: Sep 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sae-Won Han, Professor, Seoul National University Hospital: Minimal residual disease; Intensified chemotherapy
• Additional relevant MeSH terms: Colonic Neoplasms

Study Results

No Results Posted as of Sep 9, 2022