Trial Title:
Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 in Locally Advanced Colorectal Cancer
NCT ID:
NCT05571644
Condition:
Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Leucovorin
Oxaliplatin
Fluorouracil
Irinotecan
Levoleucovorin
Conditions: Keywords:
Neoadjuvant therapy
mFOLFOXIRI
Cadonilimab (AK104)
mFOLFOX6
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
mFOLFOXIRI + Cadonilimab
Description:
Cadonilimab（AK104）6mg/kg, intravenous d for 60 minutes, followed by 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) every 2 weeks for 6
cycles before surgery
Arm group label:
mFOLFOXIRI+Cadonilimab
Other name:
Oxaliplatin
Other name:
Irinotecan
Other name:
5-Fluorouracil
Other name:
Leucovorin
Other name:
Cadonilimab (AK104)
Intervention type:
Drug
Intervention name:
mFOLFOX6
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) every 2 weeks for 6 cycels before surgery
Arm group label:
mFOLFOX6
Other name:
Oxaliplatin
Other name:
5-Fluorouracil
Other name:
Leucovorin
Intervention type:
Drug
Intervention name:
mFOLFOXIRI
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) every 2
weeks for 6 cycles before surgery
Arm group label:
mFOLFOXIRI
Other name:
Oxaliplatin
Other name:
Irinotecan
Other name:
5-Fluorouracil
Summary:
Neoadjuvant chemoradiotherapy (CRT) followed by total mesenteric excision (TME) and
adjuvant chemotherapy was the standard of treatment for locally advanced rectal cancer
(LARC) in the past two decades. The main obstacles for improving survival benefit of LARC
was distant metastasis. Recently, total neoadjuvant therapy (TNT) had been recommended as
new preferred option for LARC. Induction chemotherapy with FOLFOXIRI followed by CRT or
short-course radiotherapy followed by FOLFOX chemotherapy had improved survival benefit
for LARC.
Neoadjuvant immunotherapy had also been explored in pMMR patients with CRC. In the NICHE
trial, neoadjuvant therapy with 2 dose of nivolumab and 1 dose of ipilimumab led to 29%
of pathological response and 13% of pCR. Cadonilimab (AK104) was a PD-1/CTLA-4
bi-specific antibody. Here, we tried to explore the efficacy of Neoadjuvant Treatment
With mFOLFOXIRI with or without Cadonilimab (AK104) Versus mFOLFOX6 in LARC.
Detailed description:
This study was a prospective, randomized, uncontrolled phase II trial to evaluate the
efficacy of mFOLFOXIRI combined with AK104 neoadjuvant therapy versus mFOLFOX6
neoadjuvant therapy in LARC.
The inclusion criteria: locally advanced colon cancer (T3>5mm or T4 on enhanced CT
assessment, with distant metastasis excluded); Locally advanced rectal cancer (pelvic MR
assessment as stage ii-iii, less than 12cm from the anal margin, no distant metastasis),
primary tumor location and TNM stage were stratified factors.
Group A: mFOLFOXIRI combined with Cadonilimab (AK104) for 6 cycles before surgery
Group B: 6 cycles of neoadjuvant chemotherapy with mFOLFOX6 before surgery
Group C: 6 cycles of neoadjuvant chemotherapy with mFOLFOXIRI before surgery
All groups were re-evaluated after 3 cycles and 6 cycles of treatment. If surgery was
feasible after multidisciplinary evaluation, TME resection was performed, and adjuvant
treatment was performed according to standard treatment after operation. For locally
advanced rectal cancer, preoperative pelvic enhanced MRI was used to evaluate tumor
regression after 6 cycles of preoperative treatment. For patients who still had MRF+
and/or T4 after treatment, additional short-course radiotherapy was allowed.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Aged 18-70;
2. Colorectal adenocarcinoma with definite histological evidence;
3. ECOG Performance status score is 0-1
4. Colon cancer was evaluated as T3>5mm or T4 by contrast-enhanced CT examination of
the chest, abdomen and pelvis, and distant displacement was excluded; Rectal cancer
was graded as T3-4 and/or N+ by pelvic contrast-enhanced MRI examination, and the
lower margin of the tumor was less than 12cm away from the anal margin. Distant
metastasis was excluded by chest, abdomen and pelvis CT.
5. The primary rectal tumor was assessed as complete resections by a multidisciplinary
collaboration group on colorectal cancer, including at least 2 gastrointestinal
surgeons and 1 radiologist;
6. No previous systemic antitumor therapy for colorectal cancer, including cytotoxic
drugs, immunotherapy, molecular targeted therapy, etc.;
7. Adequate organ function based on the following laboratory test values obtained
within 7 days prior to treatment:
Hemoglobin ≥90g/L, neutrophil count ≥1.5×109/L, platelet count ≥75×109/L, serum
total bilirubin ≤1.5× upper limit of normal value (UNL), aspartate transferase
≤2×UNL, alanine transferase ≤3×UNL, serum creatinine ≤1.5×UNL;
8. Willing and able to comply with research protocols and visit plans.
Exclusion Criteria:
1. The patient was complicated with obstruction, active bleeding, or perforation and
required emergency surgery or stent placement;
2. Active, known or suspected autoimmune diseases (except type I diabetes, residual
hypothyroidism requiring only hormone replacement due to autoimmune conditions, or
autoimmune diseases that are not expected to recur in the absence of external
triggers);
3. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency
syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500
IU/ml; Hepatitis C, defined as HCV-RNA above the detection limit of the assay) or
co-infection with hepatitis B and C;
4. Known allergy to the treatment drug or allergy or intolerance to its ingredients;
5. Major surgery or severe trauma, such as laparotomy, thoracotomy, laparoscopic organ
resection, etc. within the previous 4 weeks (the surgical incision should be
completely healed before enrollment);
6. Existing or coexisting other active malignancies (except those that have been
treated with curative therapy and remain disease-free for more than 5 years or
carcinoma in situ that can be cured by adequate treatment);
7. Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody
and anti-cytotoxic T-lymphocyte-associated protein 4 (Cytotoxic
T-lymphocyte-associated protein 4) antibody. Ctla-4) antibodies or other
drugs/antibodies that act on T-cell costimulatory or checkpoint pathways;
8. Had active coronary artery disease, severe/unstable angina pectoris or newly
diagnosed angina pectoris or myocardial infarction within 6 months prior to study
enrollment; Thrombotic or embolic events, such as cerebrovascular accident
(including transient ischemic attack), pulmonary embolism, deep vein thrombosis,
occurred within the previous 6 months;
9. The New York Heart Association (NYHA) class II or higher congestive Heart failure
(see Appendix 3);
10. Presence of active inflammatory bowel disease or other colorectal disease leading to
chronic diarrhea;
11. The presence of any toxicity (Common Terminology Criteria for Adverse Events, CTCAE)
(version 5.0) grade 1 or above (except anemia, alopecia, and skin pigmentation)
caused by previous treatment that has not subsided;
12. Previous or current history of pulmonary fibrosis, interstitial pneumonia,
pneumoconiosis, drug-related pneumonia, severe impairment of pulmonary function and
other lung diseases;
13. Active tuberculosis (TB), receiving anti-TB therapy or receiving anti-TB therapy
within 1 year before the first dose;
14. Persons with known syphilis infection requiring treatment;
15. Had used immunosuppressive drugs within 4 weeks before the first dose, Does not
include the nasal spray, inhalation, or other ways of topical corticosteroids or
physiological doses of systemic corticosteroids (i.e., no more than 10 mg/day
prednisone or other equivalent dose glucocorticoids), allows for prevention of
allergic reactions, or treatment of diseases such as asthma, chronic obstructive
pulmonary disease of breathing difficulties for the temporary use of glucocorticoid;
16. Receive live attenuated vaccine within 4 weeks before the first dose or during the
study period;
17. Pregnant or lactating women; Women of reproductive age (< 2 years after last
menstruation) who do not use or refuse to use effective non-hormonal contraception
or men at risk of having children.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Gastrointestinal Hospital, Sun Yat-sen University
Address:
City:
Guangzhou
Zip:
510655
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanghong Deng, PhD
Phone:
008613925106525
Email:
dengyanh@mail.sysu.edu.cn
Investigator:
Last name:
Yanhong Deng, PhD
Email:
Principal Investigator
Start date:
July 10, 2023
Completion date:
December 15, 2025
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05571644
