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

Colon Cancer Clinical Trial

— CLAUDIA  

Official title:

A Randomized Controlled Phase III Trial of Treatment Intensification in Stage II-III Colon Cancer Patients With Positive MRD During Adjuvant Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05534087
• Other study ID #: H-2205-029-1322
• Status: Recruiting
• Phase: Phase 3
• Start date: December 15, 2022
• Est. completion date: September 30, 2030

Study information

• Verified date: May 2023
• Source: Seoul National University Hospital
• Contact: Sae-Won Han, MD,PhD
• Phone: 82-2-2072-0795
• Email: saewon1[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 ) 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 236
• Est. completion date: September 30, 2030
• Est. primary completion date: September 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colon Cancer
• Colonic Neoplasms

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Jin Won Kim	Seongnam
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Circulating tumor DNA (ctDNA) clearance rate	The proportion of patients with circulating tumor DNA clearance after 36months study treatment.	The data of ctDNA clearance rate will be collected at 10 time points
Secondary	5-year overall survival rate (5y-OS rate)	Overall survival is defined as the time from beginning of study treatment until death due to any cause.	Through completion of follow-up (estimated to be 60 months)
Secondary	Treatment-Related Adverse Events	The number of patients with adverse events and the severity according to CTCAE v5.0.	Through completion of follow-up (estimated to be 36 months)
Secondary	EORTC QLQ-C30 scale	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.	Through completion of follow-up (estimated to be 36 months)