Estudio de fase III randomizado, abierto del Intergroup: Efecto de la adición de bevacizumab a quimioterapia (QT) basada en fluoropirimidinas como tratamiento en segunda línea de pacientes con cáncer colorrectal metastático que han manifestado progresión de la enfermedad durante un tratamiento de combinación con QT estándar/bevacizumab en primera línea.A randomized phase III study: Effect of adding Bevacizumab to cross over fluoropyrimidine based chemotherapy (CTx) in patients with metastatic colorectal cancer and disease progression under first-line standard CTx / Bevacizumab combination - TM

Conditions: Cáncer colorrectal metastático con progresión de la enfermedad durante un tratamiento estándar en primera línea (bevacizumab y quimioterapia basada en fluoropirimidinas / oxaliplatino, o bevacizumab y quimioterapia basada en fluoropirimidinas / irinotecan). (Los pacientes no deben ser candidatos a resección metastática primaria). Metastasic colorectal cancer

Registration Number: EUCTR2006-004634-32-ES

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 820

Inclusion Criteria

- Patients with histological confirmed diagnosis of metastatic CRC and disease progression (according to RECIST assessed by investigator, documented by CT or MRI), previously treated with first-line Therapy (Bevacizumab and Fluoropyrimidin / Oxaliplatin based or Bevacizumab and Fluoropyrimidin/ Irinotecan based CTx) and are no candidates for primary metastectomy.
- Disease Progression ? 2 months after last bevacizumab administration
- Evaluation of tumour disease according to RECIST by investigator, 4 weeks or less prior to randomization
- No major surgery within 4 weeks prior to randomization. Wound healing has to be completed
- Age ?18 years
- Life expectancy > 3 month
- ECOG ? 2
- Neutrophils ? 1.500/µl
- Platelets ? 100.000µl
- Hemoglobin > 9 g/dl
- Creatinine clearance > 30 ml/min (Dosage modification for Capecitabine if creatinine clearance < 30-50 ml/min), serum creatinine < 1,25 x upper normal limit,
- Serum bilirubin < 1,25x upper normal limit, AST / ALT < 2.5 x UNL
- In case of liver metastasis, serum bilirubin < 1,5 x upper normal limit, AST/ALT < 5 x UNL
- Signed written informed consent
- Fertile women and men of childbearing potential (<2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

?Diagnosis of progression of disease more than 2 m after last Bevacizumab (BV) administration
? First Line patients who had a PFS in first-line of < 3 m
? Patient receiving less than 3 consecutive months of BV in first line therapy
? Treatment with any other investigational agent or other biological agent (e.g. cetuximab)
? Participation in another clinical trial within 30 d prior to entering this study
? Concomitant use with St John?s Wort (for capecitabine based CTx)
? Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg
? Prior history of hypertensive crisis or hypertensive encephalopathy
? NYHA Class II or greater CHF
? History of myocardial infarction or unstable angina within 6 m prior to Day 1
? Known CNS disease, expect for treated brain metastasis (treated brain metastases are defined as having no evidence of progression or haemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging during the screening period. Anticonvulsants are allowed. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 m of start of study therapy will be excluded.
? Significant vascular disease (e.g. aortic aneurysm requiring surgical intervention, pulmonary embolism or recent peripheral arterial thrombosis) within 6 m prior start of study treatment.
? History of haemoptysis (? ½ tsp of bright red blood per episode) within 1 m prior start of study treatment
? Evidence of bleeding diathesis or significant coagulopathy (in absence of therapeutic anticoagulation)
? Major surgical procedure, open biopsy, or significant traumatic injury within 28 d prior to start of study therapy, or anticipation of need for major surgical procedure during the course of the study
? Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 d prior start of study therapy
? History of abdominal fistula or gastrointestinal perforation within 6 m prior start of study therapy.
? Serious, non healing wound, active ulcer, or untreated bone fracture
? History or evidence upon physical/neurological examination of CNS disease (unrelated to cancer) (unless adequately treated with standard medical therapy) e.g. uncontrolled seizures
? Past or current history (within the last 2 years prior to treatment start) of other malignancies except metastatic colorectal cancer (patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible)
? Known hypersensitivity to any of the study drugs
? Acute intra abdominal inflammatory process
? Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
? Patients with contraindication for cross over chemotherapy (e.g. patients treated with irinotecan based first line therapy and serious polyneuropathy > grade 1, not feasible for oxaliplatin based cross over second line therapy, or patients treated with oxaliplatin based first line therapy and hereditary fructose intolerance not feasible for Iri

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess Overall survival (OS);Secondary Objective: - To assess OS from time of starting first line therapy<br>- To assess PFS (after first progression) overall and on treatment population<br>- To evaluate the Response rate (RECIST)<br>- To evaluate the Safety profile in both arms;Primary end point(s): - To assess Overall survival (OS).

Secondary Outcome Measures