FOLFOXIRI Compared to FOLFOX in First Line Treatment of Metastatic Colorectal Cancer

• Status: Unknown status
• Trial end date: 2018-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the study is to evaluate if the exposure to all the three active cytotoxic agents (FOLFOXIRI regimen) is superior in terms of progression-free survival to conventional chemotherapy with the FOLFOX regimen as first-line treatment of chemo-naive metastatic colorectal cancer patients.

A second primary aim is to evaluate the response rate, safety and tolerability of the chemotherapy of FOLFOXIRI regimen in this patient population.

Patients will be randomized to two therapy groups:

Experimental arm A: Chemotherapy with FOLFOXIRI Standard arm B: Chemotherapy with FOLFOX

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-sen University
• Treatments: Fluorouracil; Irinotecan; Leucovorin; Levoleucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

• Signed informed consent obtained before any study specific procedures. -Subjects must be able to understand and willing to sign a written informed consent.

• Male or female subjects ≥ 18 years ≤ 75 years of age

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.(ECOG PS 0-2 for≥18 years ≤ 65 years of age ，ECOG PS 0-1 for >65 years of age)

• Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.

• There must be documentation by PET/CT scan, CT scan, MRI, or intraoperative palpation (at the time of resection of the primary colorectal tumor, if applicable) that the patient has evidence of metastases (Histologic confirmation of metastasis is not required.).

• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria measured within 4 weeks prior to registration.

• No previous chemotherapy or target therapy for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago).

• In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.

• Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:

• Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet count ≥ 100 x109/ L, hemoglobin (Hb) ≥9g/ dL.

• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN).

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.

• Alkaline phosphatase limit ≤ 5x ULN.

• Amylase and lipase ≤ 1.5 x the ULN.

• Serum creatinine ≤ 1.5 x the ULN.

• Calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min.

Exclusion Criteria:

• Previous palliative chemotherapy for metastatic disease，previous adjuvant chemotherapy including irinotecan or oxaliplatin within 6 months before random assignment.

• Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.

• Life expectancy > 12 weeks;

• Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. Subjects must have recovered from all therapy-related toxicities.

• Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks before start of study medication.

• Congestive heart failure ≤ New York Heart Association (NYHA) class 2.

• Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment or a history of ventricular arrhythmia

• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication.

• Any evidence of active infection.

• History of interstitial pneumonitis or pulmonary fibrosis

• Pregnancy or lactation at the time of study entry.

• Known dihydropyrimidine dehydrogenase (DPD) deficiency

• Any illness or medical conditions that are unstable or could jeopardize the safety of the subjects and his/her compliance in the study.

• Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea

• Subjects with known allergy to the study drugs or to any of its excipients.

• Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.

• Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).