FOLFOXIRI Compared to FOLFOX in First Line Treatment of Metastatic Colorectal Cancer
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Drug: FOLFOXIRIDrug: FOLFOX
- Registration Number
- NCT02128425
- Lead Sponsor
- Sun Yat-sen University
- Brief 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
- Detailed Description
Survival of patients with metastatic colorectal cancer is correlated with the proportion of patients who receive all the three active drugs , but not with the proportion of patients who receive any second-line therapy. A superior efficacy in PFS,ORR and OS of FOLFOXIRI has been reported with acceptable toxicity. Moreover,evidence suggests that continuous dosing metronomic chemotherapy may be more efficacious than interval-chemotherapy.
Therefore, a way to improve the outcome of metastatic colorectal cancer patients could be to administer a maintenance first-line regimen containing the three active agents.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 162
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FOLFOXIRI FOLFOXIRI FOLFOXIRI FOLFOX FOLFOX FOLFOX
- Primary Outcome Measures
Name Time Method Progression-free survival after induction and maintenance chemotherapy (PFS1) up to 18 months Progressions are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of follow up (36 months).
- Secondary Outcome Measures
Name Time Method Translational research up to 5 years toxicity and safety up to 24 months Number of participants with adverse events as a measure of safety and tolerability according to NCI CTC 4.0
QLQ (QLQ C30) - scores according to EORTC QLQ-C30 scoring manual (Quality of life) up to 36 months Progression-free survival after re-introduction of chemotherapy (PFS2) up to 24 months Response rate during re-introduction of chemotherapy up to 12 months (CR + PR rate according to RECIST)
Overall survival up to 5 years Early tumor shrinkage rate in 8 weeks after induction treatment 8 weeks
Trial Locations
- Locations (1)
Gastrointestinal Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China