Phase III study to compare two different chemotherapy treatments to determine whether the first line with the three drugs + bevacizumab followed by a second line with the same regimen may provide better results than treatment with two drugs + bevacizumab is the first and the second treatment line

• Conditions: METASTATIC COLORECTAL CANCER; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-004436-19-IT
• Lead Sponsor: G.O.N.O.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11-11
• Last Update Posted: 16 February 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

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 < or = 2 if aged < 71 years, ECOG PS = 0 if aged 71-75 years
-Life expectancy of at least 12 weeks
-Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse
-Neutrophils >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) <2.5 x UNL (or <5 x UNL in case of liver metastases) alkaline phosphatase <2.5 x UNL (or <5 x UNL in case of liver metastases)
-Creatinine clearance >50 mL/min or serum creatinine 1.5 x UNL
-Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate <1 g of protein/24 hr
-Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.
-Subjects and their partners must be willing to avoid pregnancy during the trial and until 6 months after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore,
be willing to use adequate contraception as approved by the investigator (barriere contraceptive measure or oral contraception)
-Will and ability to comply with the protocol
-Written informed consent to study procedures and to molecular analyses.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 354

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified