METASTATIC COLORECTAL CANCER
Conditions
Interventions
Trade Name: Avastin
Product Name: Bevacizumab
Product Code: Bevacizumab
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: FLUOROURACILE TEVA* 500mg/10 ml
Product Name: 5 Fluor
Sponsors
G.O.N.O.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Histologically proven diagnosis of colorectal cancer -Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease -At least one measurable lesion according to RECIST1.1 criteria -Availability of a tumoral sample -Male or female of 18-75 years of age -ECOG PS 1.5 x 109/L, Platelets >100 x 109/L, Hgb >9 g/dl -Total bilirubin 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) 50 mL/min or serum creatinine 1.5 x UNL -Urine dipstick of proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range 354
Exclusion criteria
Exclusion criteria: Radiotherapy to any site within 4 weeks before the study -Previous adjuvant oxaliplatin-containing chemotherapy -Previous treatment with bevacizumab -Untreated brain metastases or spinal cord compression or primary brain tumours -History or evidence upon physical examination of CNS disease unless adequately treated -Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria -Serious, non-healing wound, ulcer, or bone fracture -Evidence of bleeding diathesis or coagulopathy -Uncontrolled hypertension and prior histor of hypertensive crisis or hypertensive encephalopathy -Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (=6 months), myocardial infarction (=6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication -Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment. -Any previous venous thromboembolism > NCI CTCAE Grade 3. -History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment. -Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes Chronic, daily treatment with high-dose aspirin (>325 mg/day) -Treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer) -Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ -Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study -Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication -Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barriere contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this trial is to compare the efficacy of the two proposed treatment strategies in terms of duration of Progression Free Survival 2 (PFS2).;Secondary Objective: Secondary objectives of this study are to compare the two proposed treatment strategies in terms of: -Duration of Progression Free Survival (PFS); -Duration of 2nd-Progression Free Survival (2nd-PFS); -Duration of Time to Failure of Strategy (TFS); -Duration of Overall Survival (OS); -Distribution of Objective Response Rate (ORR) during first- and second-line treatment; -Distribution of Early Objective Response (EOR) during first-line treatment; -Distribution of the rate of secondary R0 resection of metastases; -Safety profile; -Translational analyses. ;Primary end point(s): The primary endpoint is Progression Free Survival 2 (PFS2). PFS2 will be defined as beginning with randomization and ending with the first of the following events: a) death; b) disease progression on any treatment given after 1st progression. For patients that will not receive any treatment within 3 months after 1st progression, PFS2 will be equal to PFS. The determination of disease progression will be based on investigator-reported measurements. Disease status will be evaluated according to RECIST 1.1 criteria. Censoring rules for PFS2 will be: end of study without PD, loss at follow-up. Curative surgery for metastasis will not result in censoring for PFS2. PFS2 will be analyzed both in the intention-to-treat population (primary analysis) and in the per-protocol population.;Timepoint(s) of evaluation of this end point: every 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints of this study are the following: Progression free survival (PFS) is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive, on study and progression free at the time of the analysis. Alive patients having no tumor assessments after baseline will have time to event censored on the date of randomization.2nd-Progression free survival (2nd-PFS) is defined as the time from the beginning of the second-line treatment to the documentation of objective disease progression or death due to any cause, whichever occurs first. 2nd-PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive, on study and 2nd-progression free at the time of the analysis. 2nd-PFS will be analyzed both in the intention-to-treat population (whichever 2nd-line treatment will be adopted) and in the per-protocol population. Time to failure of strategy (TFS) is defined as the time time from randomization to the first of the following events: death; patient requires the addition of a new therapeutic agent (i.e. an agent not included in the original strategy); patient experiences disease progression while being treated with all agents that are components of the initial treatment strategy (except for agents which cannot be used because of persistent toxicity or contraindications); or patient experiences disease progression during a partial or complete treatment holiday from initial treatment strategy and receives no further therapy within 3 months. Subjects who did not have an event as stated above while on study will be censored at the last evaluable radiographic assessment date. TFS will be analyzed both in the intention-to-treat po | — |
Countries
Italy
Contacts
Public ContactU.O.Oncologia Medica2Universitaria
Azienda Ospedaliero-Universitaria Pisana
Outcome results
None listed