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

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: mFOLFOXIRI; Drug: mFOLFOX6

• Study Type: Interventional
• Enrollment (Anticipated): 340
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yanhong Deng, Ph.D.; Phone Number: 008613925106525; Email: dengyanh@mail.sysu.edu.cn
• Study Contact Backup: Name: Jianwei Zhang, Ph.D.; Phone Number: 00862013480216906; Email: zhangjw25@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Postoperative CT scan showed distant meatstasis
2. Patients with postoperative obstruction or active bleeding
3. 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)
4. The time from postoperative to start of adjuvant therapy has exceeded 8 weeks
5. Patients who have received neoadjuvant therapy
6. Active coronary artery disease, severe/unstable angina or newly diagnosed angina or myocardial infarction within 12 months prior to study participation
7. Thrombotic or embolic events within the past 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, deep vein thrombosis
8. Unstable or any medical condition that affects patient safety and study compliance
9. Subjects with known allergy to the study drugs or to any of its excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: Leucovorin; Irinotecan; 5-Fluorouracil; Oxaliplatin
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: Leucovorin; 5-Fluorouracil; Oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Disease-free Survival (DFS)	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.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	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 years
3-year distant metastatic-free survival （DMFS）	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.	3 year

Collaborators and Investigators

• Sponsor: Yanhong Deng
• Investigators: Principal Investigator: Yanhong Deng, Ph.D., Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 9, 2022
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): July 1, 2027

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Actual): October 7, 2022
• Last Update Submitted That Met QC Criteria: October 6, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Adjuvant chemotherapy; mFOLFOXIRI; mFOLFOX6; minimal residual disease (MRD)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Levoleucovorin
• Other Study ID Numbers: GIHSYSU-24 (Other Identifier: The Sixth Affiliated Hospital of Sun Yat-sen University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No