Adjuvant mFOLFOXIRI vs. mFOLFOX6 in MRD Positive Stage II-III Colorectal Cancer (AFFORD)

Sponsor

Yanhong Deng (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05427669

Collaborator

(none)

340

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Surgery is the main treatment method for colon cancer. About 50% of patients can be cured with surgery alone. For colon cancer with high-risk stage II or III after surgery, the current guidelines recommend 3-6 months after surgery. adjuvant chemotherapy to reduce the risk of recurrence and metastasis. However, for this part of the population, the overall benefit of adjuvant chemotherapy is limited, and different high-risk factors have different weights; some patients will still experience recurrence and metastasis even after receiving adjuvant chemotherapy. A number of previous studies have shown that patients with a positive ctDNA test on postoperative liquid biopsy without postoperative adjuvant therapy have a recurrence risk of 70-80%. Even if they receive adjuvant chemotherapy, the recurrence risk is significantly higher than that of ctDNA-negative patients. ctDNA has received increasing attention as a predictor of postoperative recurrence risk.

This study intends to randomly assign 1:1 to mFOLFOXIRI regimen adjuvant chemotherapy for 6 months and mFOLFOX6 regimen for colon cancer patients with postoperative high-risk stage II-III and liquid biopsy results within 1 month after surgery. Adjuvant chemotherapy was performed for 6 months, ctDNA was dynamically monitored after 3 months of treatment and at the end of adjuvant therapy. During the follow-up period, CEA was reviewed every 3 months, and chest, abdomen, and pelvis CT and ctDNA were reviewed every 6 months; the primary endpoint of the study was 2 years RFS, secondary endpoints included 3-year DFS, OS, safety and tolerability. Through intensive postoperative adjuvant therapy, we hope to screen colon cancer patients with high recurrence risk to receive adjuvant chemotherapy and improve the survival prognosis of ctDNA-positive colon cancer patients.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: mFOLFOXIRI Drug: mFOLFOX6	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

340 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Adjuvant Modified FOLFOXIRI Versus mFOLFOX6 in Patients With Postoperative MRD Positive Stage II-III Colorectal Cancer: A Multicenter, Open Lable Randomized Phase 3 Study (AFFORD)

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mFOLFOXIRI Patients will receive mFOLFOXIRI chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy	Drug: mFOLFOXIRI mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 12 cycles at the most Other Names: Oxaliplatin Irinotecan 5-Fluorouracil Leucovorin
Active Comparator: mFOLFOX6 Patients will receive mFOLFOX6 chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy	Drug: mFOLFOX6 mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 12 cycles at the most Other Names: Oxaliplatin 5-Fluorouracil Leucovorin

Arm

Intervention/Treatment

Experimental: mFOLFOXIRI

Patients will receive mFOLFOXIRI chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy

Drug: mFOLFOXIRI

mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 12 cycles at the most

Other Names:

Oxaliplatin

Irinotecan

5-Fluorouracil

Leucovorin

Active Comparator: mFOLFOX6

Patients will receive mFOLFOX6 chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy

Drug: mFOLFOX6

mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 12 cycles at the most

Other Names:

Oxaliplatin

5-Fluorouracil

Leucovorin

Outcome Measures

Primary Outcome Measures

3-year Disease-free Survival (DFS) [3 years]
The DFS is defined as the time from the start of treatment to the date of first documented recurrence or metastais or death as a result of any cause, whichever occurred first.

Secondary Outcome Measures

Overall survival [3 years]
OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
3-year distant metastatic-free survival （DMFS） [3 year]
The DMFS is defined as the time from the start of treatment to the date of first documented distant metastais or death as a result of any cause, whichever occurred first.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-70 years old
Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
ECOG performance status 0-1
Upfront surgery (R0 resection) and postoperative pathological stage II -III and the circulating tumor DNA (ctDNA) test results show that MRD was positive
Randomization must be within 8 weeks after surgery.
No distant metastasis after surgery
Appropriate organ function

Exclusion Criteria:

Postoperative CT scan showed distant meatstasis
Patients with postoperative obstruction or active bleeding
Other active malignant tumors in the past or at the same time (except for malignant tumors that have received curative treatment and have no disease for more than 5 years or carcinoma in situ that can be cured by adequate treatment)
The time from postoperative to start of adjuvant therapy has exceeded 8 weeks
Patients who have received neoadjuvant therapy
Active coronary artery disease, severe/unstable angina or newly diagnosed angina or myocardial infarction within 12 months prior to study participation
Thrombotic or embolic events within the past 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, deep vein thrombosis
Unstable or any medical condition that affects patient safety and study compliance
Subjects with known allergy to the study drugs or to any of its excipients.