Clinical trial NCT02128425: FOLFOXIRI Compared to FOLFOX in First Line Treatment of Metastatic Colorectal Cancer
Official title: Phase II Randomized Controlled Trial of FOLFOXIRI Compared to FOLFOX in First Line Treatment of Chemo-naive Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Colorectal cancer
Metastatic colorectal cancer
FOLFOXIRI
FOLFOX
Oxaliplatin
irinotecan
Leucovorin
5-FU
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2014-05-01
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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).

Primary outcomes:
measure: Progression-free survival after induction and maintenance chemotherapy (PFS1)
timeFrame: up to 18 months
Secondary outcomes:
measure: Progression-free survival after re-introduction of chemotherapy (PFS2)
timeFrame: up to 24 months
measure: Response rate during re-introduction of chemotherapy
timeFrame: up to 12 months
measure: Early tumor shrinkage rate in 8 weeks after induction treatment
timeFrame: 8 weeks
measure: Overall survival
timeFrame: up to 5 years
measure: toxicity and safety
timeFrame: up to 24 months
measure: QLQ (QLQ C30) - scores according to EORTC QLQ-C30 scoring manual (Quality of life)
timeFrame: up to 36 months
measure: Translational research
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Gastrointestinal Hospital, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sixth Affiliated Hospital, Sun Yat-sen University
name: Yanhong Deng, M.D.
role: PRINCIPAL_INVESTIGATOR
References: