Clinical trial NCT04922853: Comparison of the Pathological Effect Between 2 and 4 Cycles Neoadjuvant CAPOX for Low/Intermediate Risk II/III Rectal Cancer
Official title: Comparison of the Pathological Effect Between 2 and 4 Cycles Neoadjuvant CAPOX for Low/Intermediate Risk II/III Rectal Cancer：a Prospective, Non-inferior, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rectal Cancer
Neoadjuvant Chemotherapy
Lead sponsor: West China Hospital
Sponsor class: OTHER
Collaborators: name: The Third People's Hospital of Chengdu
name: Chengdu Fifth People's Hospital
name: Peking Union Medical College
name: Peking University Cancer Hospital & Institute
name: Sun Yat-sen University
name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Yunnan Cancer Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: The Affiliated Hospital Of Guizhou Medical University
name: Sichuan Provincial People's Hospital
name: Nanchong Central Hospital
name: Dazhou Central Hospital
name: Leshan People's Hospital
name: GeneCast Biotechnology Co., Ltd.
First posted: 2021-06-11
Enrollment: 554
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the pathological effect between 2 cycles and 4 cycles of Capox regimen as neoadjuvant chemotherapy for low/ intermediate risk stage II/III rectal cancer.

Detailed description: Neoadjuvant Chemotherapy alone has showed much benefit for low/ intermediate risk stage II/III rectal cancer which would be verified by the PROSPECT trial. However, the effect of the Neoadjuvant chemotherapy was heterogeneous in different patients. It's important to verify those chemo-resistant cases as early as possible. So that, this trial will compare the pathological effect between 2 cycles and 4 cycles of Capox regimen as neoadjuvant chemotherapy for low/ intermediate risk stage II/III rectal cancer to explore whether those chemotherapeutic non-responders after 2 cycles Capox was non-inferior to those after 4 cycles chemotherapy.

Eligibility criteria: Inclusion Criteria:

1. Age: 18-75 years old; No gender limitation;
2. Patients diagnosed with low/intermediate risk stage II/III rectal cancer under MRI and transanal ultrasound,defined as: low:T3a-bN0-1M0, EMVI (±), MRF (-) (≥2mm); Middle-high rectal cancer: T3a-cN0-1M0, EMVI (±), MRF (-) (≥2mm); No more than 3 lymph nodes with short diameter over 8mm or highly suspected metastases; Patients with very low rectal cancer who met the above criteria and could achieve negative circumferential resection margin under ELAPE surgery could be included in the group
3. tumor located \<=12cm from anal verge by colonoscopy or anal examination
4. no distant metastasis confirmed by CT examination;
5. rectal adenocarcinoma confirmed by pathology,
6. ECOG score: 0-1;
7. Patients with primary rectal cancer who did not receive surgery (except palliative stomy), radiotherapy, systemic chemotherapy or other anti-tumor therapy before enrollment;
8. Main organs function normally, that is, meet the following characteristics: ① Blood routine examination criteria should meet: Hb ≥9g/dL, WBC ≥ 3.5/4.0×109/L, neutrophils ≥ 1.5×109/L, PLT≥ 100×109/L. ② Biochemical tests should meet the following criteria: CREA and BIL ≤ 1.0 times upper limit of normal (ULN), ALT and AST≤ 2.5 times upper limit of normal (ULN), alkaline phosphatase (ALP) ≤2.5×UNL, total bilirubin (TBIL) ≤1.5×UNL.
9. No history of allergy to platinum drugs when no 5-FU drugs are allergic;
10. Women of childbearing age must have had a pregnancy test (serum or urine) 7 days prior to enrolment, be negative, and be willing to use an appropriate method of contraception during the trial and 8 weeks after the last dosing. For men, surgical sterilization or consent to use an appropriate method of contraception during the trial or for 8 weeks after the last dosing;
11. Subjects volunteered to participate in this study, signed the informed consent, and showed good compliance and followed up.

Exclusion Criteria:

1. patients suspect to Lynch syndrome;
2. Patients showed distant metastasis during treatment;
3. Previously or coexisting malignancies (including concurrent colon cancer), except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
4. pregnant or breastfeeding women;
5. Patients with severe cardiovascular diseases and diabetes that is not easily controlled;
6. People with mental disorders;
7. Severe infection;
8. sever renal disfunction;
9. History of gastrointestinal fistula, perforation, bleeding, or severe ulcer;
10. Allergic to 5-FU or platinum;
11. The presence of serious gastrointestinal diseases that affect the absorption of oral chemotherapeutic drugs; (12) Participants in additional clinical trials within 4 weeks prior to the start of treatment.

Primary outcomes:
measure: pathological Tumor Regression Grade evaluation
timeFrame: 12 weeks
Secondary outcomes:
measure: rate of chemotherapeutic complication
timeFrame: 12 weeks
measure: 3-year overall survival
timeFrame: 3 year after recruiting
measure: disease free survival
timeFrame: 3 year after recruiting
measure: cumulative distant recurrence rate
timeFrame: 3 year after recruiting
measure: cumulative local recurrence rate
timeFrame: 3 year after recruiting
Other outcomes:
Locations:
city: Wuxi
country: China
facility: Genecast Biotechnology Co., Ltd
state: Jiangsu
city: Chengdu
country: China
facility: the Third People'S Hospital of Chengdu
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
city: Kunming
country: China
facility: The Third Affiliated Hospital of Kunming Medical University
state: Yunnan
Study officials:
References: