Adjuvant mFOLFOXIRI vs. mFOLFOX6 in MRD Positive Stage II-III Colorectal Cancer (AFFORD) (AFFORD)
Primary Purpose
Colorectal Cancer
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
mFOLFOXIRI
mFOLFOX6
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Adjuvant chemotherapy, mFOLFOXIRI, mFOLFOX6, minimal residual disease (MRD)
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
mFOLFOXIRI
mFOLFOX6
Arm Description
Patients will receive mFOLFOXIRI chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy
Patients will receive mFOLFOX6 chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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-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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05427669
Brief Title
Adjuvant mFOLFOXIRI vs. mFOLFOX6 in MRD Positive Stage II-III Colorectal Cancer (AFFORD)
Acronym
AFFORD
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 9, 2022 (Anticipated)
Primary Completion Date
July 1, 2025 (Anticipated)
Study Completion Date
July 1, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Yanhong Deng
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
Adjuvant chemotherapy, mFOLFOXIRI, mFOLFOX6, minimal residual disease (MRD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
340 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
mFOLFOXIRI
Arm Type
Experimental
Arm Description
Patients will receive mFOLFOXIRI chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy
Arm Title
mFOLFOX6
Arm Type
Active Comparator
Arm Description
Patients will receive mFOLFOX6 chemotherapy once every two weeks for at the most 12 cycles as adjuvant therapy
Intervention Type
Drug
Intervention Name(s)
mFOLFOXIRI
Other Intervention Name(s)
Oxaliplatin, Irinotecan, 5-Fluorouracil, Leucovorin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
mFOLFOX6
Other Intervention Name(s)
Oxaliplatin, 5-Fluorouracil, Leucovorin
Intervention Description
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
Primary Outcome Measure Information:
Title
3-year Disease-free Survival (DFS)
Description
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.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
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.
Time Frame
3 years
Title
3-year distant metastatic-free survival (DMFS)
Description
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.
Time Frame
3 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yanhong Deng, Ph.D.
Phone
008613925106525
Email
dengyanh@mail.sysu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Jianwei Zhang, Ph.D.
Phone
00862013480216906
Email
zhangjw25@mail.sysu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yanhong Deng, Ph.D.
Organizational Affiliation
Sixth Affiliated Hospital, Sun Yat-sen University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Adjuvant mFOLFOXIRI vs. mFOLFOX6 in MRD Positive Stage II-III Colorectal Cancer (AFFORD)
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