FOLFOXIRI for Neoadjuvant Treatment of High-risk Locally Advanced Colorectal Cancer

NCT05018182 | Unknown Phase 2

• 1 other identifier: 2021-010
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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.

Conditions

High-risk Locally Advanced Colorectal Cancer; Neoadjuvant Chemotherapy; FOLFOXIRI Regimen

Outcome Measures

Primary Outcomes (1)

• Pathological response

  The rate of Tumor Regression Grade 0-1 in the resected tumour tissue

  up to 24 weeks

Secondary Outcomes (10)

• Objective Response Rate (ORR)

  up to 24 weeks

• Pathologic Complete Response (PCR)

  up to 24 weeks

• R0 resection rate

  up to 24 weeks

• Progression Free Survival (PFS)

  up to 3 years

• Distant metastasis-free survival Metastasis-free survival

  up to 3 years

Study Arms (1)

Neoadjuvant chemotherapy

EXPERIMENTAL

4 cycles of neoadjuvant chemotherapy with FOLFOXIRI + operation + 5 cycles of adjuvant chemotherapy with XELOX

Drug: Oxaliplatin; Drug: Irinotecan; Drug: Folinic Acid; Drug: 5FU; Drug: Capecitabine

Interventions

Oxaliplatin DRUG

Oxaliplatin 85 mg/m² Q2w(2 h) before surgery rection and 130 mg/m² Q3w (2 h) after surgery

Also known as: Eloxatin

Neoadjuvant chemotherapy

Irinotecan DRUG

Irinotecan 150 mg/m² ivgtt(1.5 h) Q2w before surgery rection

Also known as: Campto

Neoadjuvant chemotherapy

Folinic Acid DRUG

Folinic acid 400 mg/m² ivgtt(2 h) Q2w before surgery rection

Also known as: Leukovorin

Neoadjuvant chemotherapy

5FU DRUG

5-FU 2800 mg/m² civ(46 h) Q2w before surgery rection

Also known as: 5-Fluorouracil

Neoadjuvant chemotherapy

Capecitabine DRUG

Capecitabine 1000mg/m² d1-14 po Q3w after surgery rection

Also known as: Xeloda

Neoadjuvant chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

Sichuan University West China Hospital

Chengdu, Sichuan, 610044, China

RECRUITING

Related Publications (1)

• Chen X, Leng W, Zhou Y, Yu Y, Meng W, Cao P, Wang Z, Qiu M. Pathological response and safety of FOLFOXIRI for neoadjuvant treatment of high-risk relapsed locally advanced colon cancer: study protocol for a single-arm, open-label phase II trial. BMJ Open. 2023 Jan 31;13(1):e062659. doi: 10.1136/bmjopen-2022-062659.

  PMID: 36720570 DERIVED

MeSH Terms

Interventions

Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil; Capecitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Weibing Leng, Ph.D

  Sichuan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meng Qiu, Ph.D

CONTACT

+8602885423203; qiumeng@wchscu.cn

Weibing Leng, Ph.D

CONTACT

+8602885423203; s103470@stu.scu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: August 3, 2021
• First Posted: August 24, 2021
• Study Start: August 2, 2021
• Primary Completion: April 1, 2022
• Study Completion: August 2, 2022
• Last Updated: August 24, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)