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

Neoadjuvant Chemotherapy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05018182
• Other study ID #: 2021-010
• Status: Recruiting
• Phase: Phase 2
• Start date: August 2, 2021
• Est. completion date: August 2, 2022

Study information

• Verified date: August 2021
• Source: West China Hospital
• Contact: Meng Qiu, Ph.D
• Phone: +8602885423203
• Email: qiumeng[@]wchscu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 69
• Est. completion date: August 2, 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Neoadjuvant Chemotherapy

Intervention

Drug:
• Oxaliplatin
Oxaliplatin 85 mg/m² Q2w(2 h) before surgery rection and 130 mg/m² Q3w (2 h) after surgery
• Irinotecan
Irinotecan 150 mg/m² ivgtt(1.5 h) Q2w before surgery rection
• Folinic Acid
Folinic acid 400 mg/m² ivgtt(2 h) Q2w before surgery rection
• 5FU
5-FU 2800 mg/m² civ(46 h) Q2w before surgery rection
• Capecitabine
Capecitabine 1000mg/m² d1-14 po Q3w after surgery rection

Locations

Country	Name	City	State
China	Sichuan University West China Hospital	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
West China Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological response	The rate of Tumor Regression Grade 0-1 in the resected tumour tissue	up to 24 weeks
Secondary	Objective Response Rate (ORR)	Rate of patients with partial or complete response according to modified RECIST criteria.	up to 24 weeks
Secondary	Pathologic Complete Response (PCR)	Rate of pathological complete response in the resected tumour tissue	up to 24 weeks
Secondary	R0 resection rate	Resection rate, defined as patients with microscopically complete (R0) resection (ITT- population)	up to 24 weeks
Secondary	Progression Free Survival (PFS)	Progression free survival (Medium, Kaplan-Meier-estimation, ITT- population)	up to 3 years
Secondary	Distant metastasis-free survival Metastasis-free survival	distant Distant metastasis-free survival (Medium, Kaplan-Meier-estimation, ITT- population)	up to 3 years
Secondary	Overall survival	Overall survival (Kaplan-Meier-estimation, ITT- population)	up to 3 years
Secondary	Toxicity and Compliance to study treatment	Toxicity according to NCI-CTC criteria v. 4.0 Perioperative toxicity according to Clavien	up to 1 years
Secondary	Molecular markers	Evaluation of molecular predictive markers for response and toxicity	up to 1 years
Secondary	Quality of Life to study treatment	scores of Quality of Life Questionare-Core 30 of the European Organization for Research and Treatment of Cancer	up to 1 years
Secondary	Number of patients with 30-day post-operative mortality		up to 24 weeks