Clinical trial NCT01163396: First-line FOLFOXIRI In Combination With Bevacizumab For Metastatic Colorectal Cancer
Official title: Open-label, Multicenter, Phase II Study Of First-line Biweekly Irinotecan, Oxaliplatin And Infusional 5-FU/LV (FOLFOXIRI) In Combination With Bevacizumab In Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer Metastatic
Lead sponsor: Gruppo Oncologico del Nord-Ovest
Sponsor class: OTHER
First posted: 2010-07-15
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, open-label, multicentre phase II study evaluating the safety and efficacy of the combination of the G.O.N.O. FOLFOXIRI regimen with bevacizumab as first-line treatment of metastatic colorectal cancer.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed colorectal adenocarcinoma
* Unresectable and measurable metastatic disease (RECIST criteria)
* Male or female, aged \> 18 years and ≤ 75 years
* ECOG Performance Status (PS) \< 2 if aged \< 71 years
* ECOG PS = 0 if aged 71-75 years
* Life expectancy of more than 3 months
* Adequate haematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL
* INR ≤ 1.5 and aPTT ≤ 1.5 x ULN within 7 days prior to starting study treatment
* Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases \< 5 x ULN)
* Serum Creatinine ≤ 1.5 x ULN
* Urine dipstick for proteinuria \< 2+. If urine dipstick is ≥ 2+, 24- hour urine must demonstrate ≤ 1 g of protein in 24 hours
* Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse
* At least 6 weeks from prior radiotherapy and 4 weeks from surgery

Exclusion Criteria:

* Prior palliative chemotherapy
* Prior treatment with bevacizumab
* Bowel obstruction (or subobstruction)
* History of inflammatory enteropathy or extensive intestinal resection (\> hemicolectomy or extensive small intestine resection with chronic diarrhea)
* Symptomatic peripheral neuropathy \> 2 grade NCIC-CTG criteria
* Presence or history of CNS metastasis
* Active uncontrolled infections
* Active disseminated intravascular coagulation
* Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment, or anticipation of the need for major surgery during the course of the study
* Central Venous Access Device (CVAD) for chemotherapy administration inserted within 2 days prior to study treatment start
* Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix
* Clinically significant cardiovascular disease, for example cerebrovascular accidents (CVA) (≤ 6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia
* Uncontrolled hypertension
* 24-hour urine protein \> 1 g if dipstick \> 2+
* History of thromboembolic or hemorrhagic events within 6 months prior to treatment
* Evidence of bleeding diathesis or coagulopathy
* Serious, non healing wound/ulcer or serious bone fracture
* No therapeutic anticoagulation or antiplatelet agents or NSAID with anti-platelet activity (aspirin ≤ 325 mg/day allowed)
* Pregnancy or lactation
* Fertile women (\< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: PFS rate at 10 months from study entry
Secondary outcomes:
measure: Response rate (RR)
timeFrame: 2007-2010
measure: Overall survival (OS)
timeFrame: 2007-2010
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 2007-2010
measure: Evaluation of potential surrogate markers predictive of bevacizumab activity
timeFrame: 2007-2010
Other outcomes:
Locations:
Study officials:
affiliation: University of Pisa
name: Alfredo Falcone, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cremolini C, Casagrande M, Loupakis F, Aprile G, Bergamo F, Masi G, Moretto R R, Pietrantonio F, Marmorino F, Zucchelli G, Tomasello G, Tonini G, Allegrini G, Granetto C, Ferrari L, Urbani L, Cillo U, Pilati P, Sensi E, Pellegrinelli A, Milione M, Fontanini G, Falcone A. Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest. Eur J Cancer. 2017 Mar;73:74-84. doi: 10.1016/j.ejca.2016.10.028. Epub 2016 Dec 13.
citation: Masi G, Loupakis F, Salvatore L, Fornaro L, Cremolini C, Cupini S, Ciarlo A, Del Monte F, Cortesi E, Amoroso D, Granetto C, Fontanini G, Sensi E, Lupi C, Andreuccetti M, Falcone A. Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol. 2010 Sep;11(9):845-52. doi: 10.1016/S1470-2045(10)70175-3. Epub 2010 Aug 9.