Clinical trial NCT05018182: FOLFOXIRI for Neoadjuvant Treatment of High-risk Locally Advanced Colorectal Cancer
Official title: To Observe the Pathological Remission Rate and Safety of FOLFOXIRI for Neoadjuvant Treatment of High-risk Locally Advanced Colorectal Cancer With a Single-arm, Open, Prospective Phase II Exploratory Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: High-risk Locally Advanced Colorectal Cancer
Neoadjuvant Chemotherapy
FOLFOXIRI Regimen
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2021-08-24
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main cause of recurrence after surgical treatment of colorectal cancer is distant metastasis. Neoadjuvant chemotherapy has potential benefits of improving the effectiveness of chemotherapy. Preoperative chemotherapy may eradicate microscopic metastatic cancer cells earlier than adjuvant chemotherapy, reduce cancer cell spillage during surgery, and lessen the invasiveness of surgical resection. The FOLFOXIRI regimen has been shown to have a high objective efficiency in advanced colorectal cancer. This phase II trial is to explore the pathological remission rate and safety of stage II/III locally advanced colon cancer with high risk of recurrence to FOLFOXIRI regimen of neoadjuvant chemotherapy alone.


Eligibility criteria: Inclusion Criteria:

* Age: 18-75 years old; Sex: Male or female;
* WHO performance status of 0, 1 or 2
* Histologically proven colorectal carcinoma (defined as cancer that is located \>10 cm from the anal verge by endoscopy)
* Unequivocal radiological evidence of locally advanced cancer based on thin slice spiral CT \[defined as T4a/b or (and) N2 / fused lymph nodes or (and) positive extramural vascular invasion (EMVI +) or (and) circumferential resection margin (CRM) ≤ 2mm\].
* No distant metastases (distant organ or (and) distant lymph node metastases) assessed by CT scan or other radiographic examination.
* For patients with T4b, R0 resection was expected to be achieved, including the necessary combined organ resection，by MDT discussion.
* No history of 5-Fu and platinum drug allergy.
* Adequate bone marrow function: Hb\>9g/dl; PLT \>100 x 10\^9/l; WBC \>3.5 x 10\^9/l and ANC ≥1.5x10\^9/l.
* Adequate hepatobiliary function: ASAT (aspartate aminotransferase) and ALAT (alanine aminotransferase) of 2.5 x ULN (upper limits of normal) or less, Alkaline phosphatase of 2.5 x ULN or less, total bilirubin 1.5 x upper normal level or less.
* Adequate renal biochemistry: GFR \>50 ml/min calculated by the Wright or Cockroft formula or EDTA clearance \>70 ml/min.
* For female and of childbearing potential, patient must have a negative pregnancy test ≤72hours prior to initiating study treatment and agree to avoid pregnancy during and for 6 months after study treatment. For male with a partner of childbearing potential, patient must agree to use adequate, medically approved, contraceptive precautions during and for 90 days after the last dose of study treatment
* Patient able and willing to provide written informed consent for the study.

Exclusion Criteria:

* Patients with lynch syndrome
* Rectal cancer located 10 cm or less from the anal verge.
* Any patient for whom radiotherapy is advised by the MDT.
* Patient with evidence of distant metastases or peritoneal nodules (M1).
* Severe intestinal complications on initial clinical or imaging assessment: perforation, obstruction, uncontrollable bleeding.
* Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery.
* Pre-existing or concurrent other malignancies (including concurrent colon cancer), except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix.
* Pregnant or breastfeeding women.
* Patients with severe cardiovascular disease and diabetes mellitus that cannot be easily controlled.
* Persons with mental disorders.
* Patients with severe infections.
* Patients on thrombolytic/anticoagulant therapy, bleeding quality or coagulation disorders; or aneurysms, strokes, transient ischemic attacks, arteriovenous malformations in the past year.
* Previous history of renal disease with urine protein on urinalysis or clinically significant renal function abnormalities.

Primary outcomes:
measure: Pathological response
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to 24 weeks
measure: Pathologic Complete Response (PCR)
timeFrame: up to 24 weeks
measure: R0 resection rate
timeFrame: up to 24 weeks
measure: Progression Free Survival (PFS)
timeFrame: up to 3 years
measure: Distant metastasis-free survival Metastasis-free survival
timeFrame: up to 3 years
measure: Overall survival
timeFrame: up to 3 years
measure: Toxicity and Compliance to study treatment
timeFrame: up to 1 years
measure: Molecular markers
timeFrame: up to 1 years
measure: Quality of Life to study treatment
timeFrame: up to 1 years
measure: Number of patients with 30-day post-operative mortality
timeFrame: up to 24 weeks
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Sichuan University West China Hospital
state: Sichuan
Study officials:
affiliation: Sichuan University
name: Weibing Leng, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: