A single-arm, open-label phase II study: Treatment beyond progression by adding Bevacizumab to XELOX or FOLFOX chemotherapy in patients with metastatic colorectal cancer and disease progression, under first-line FOLFIRI + bevacizumab combination - AVASTAY
- Conditions
- Metastatic colorectal cancer with disease progression under first-line FOLFIRI + Bevacizumab combination (Patients no candidates for primary metastectomy)MedDRA version: 14.1Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2009-012090-36-BE
- Lead Sponsor
- .V. Roche S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
- Patients with histological onfirmed diagnosis of metastatic CRC and disease progression (according to RECIST assessed by investigator, documented by CT or MRI) previously treated with first-line therapy (FOLFIRI + Bevacizumab) until progression and who are no candidates for primary metastectomy.
- At least one measurable lesion according to RECIST version 1.1
- Disease Progression = 8 weeks after last bevacizumab administration.
- No more than 8 weeks between last administration 1st line treatment with FOLFIRI + bevacizumab and start 2nd line XELOX or FOLFOX + Bevacizumab
- Evaluation of tumor disease according to RECIST by investigator, 4 weeks or less prior inclusion.
- No major surgery within 4 weeks prior to inclusion
- Wound healing completed
- Age = 18 years
- Life expectancy > 3 months
- ECOG = 2
- Neutrophils = 1.500/µL
- Platelets = 100.000/µL
- Hemoglobin > 9 g/dL
- Creatinine clearance > 30mL/min (Dosage modification for Capecitabine 1250 mg/m² bid if creatinine clearance < 30-50 mL/min), serum creatinine < 1,25 x upper normal limit
- Serum bilirubin < 1,25 x upper normal limit, AST/ALT < 2.5 x ULN
- In case of liver metastasis, serum bilirubin < 1,5 x upper normal limit, AST/ALT < 5 x ULN
- Signed written informed consent
- Fertile women (< 2 years after last menstruation) and men of childbearing potential 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
- Diagnosis of progression of disease more than 8 weeks after last Bevacizumab administration
- Current and/or previous treatment with any other investigational agent or other biological agent (e.g. cetuximab)
- Participation in another clinical trial (except for the non-interventiolal trial ML22517 - Avastart) within 30 days prior to entering this study
- Inadequately controlled hypertension (definded 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 months prior to Day 1
- Known CNS disease, except for treated brain metastasis (treated brain metastasis are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvultants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radio surgery (RS; Gamma Knife; LINAC; or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months 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 months prior start of study treatment.
- History of haemoptysis (= ½ teaspoon of bright red blood per episode) within 1 month prior to 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 days 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 vascular access device, within 7 days prior start of study therapy
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to 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 oxaliplatin containing chemotherapy (e.g. patients with serious polyneuropathy > grade 1, not feasible for oxaliplatin based treatment beyond progression).
- Previous radiotherapy: Patients must have recovered from any radiotherapy toxicity prior to enrolment
- Contraindication for CTX regimen as indicated in re
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess Progression Free Survival (PFS) of treatment beyond progression therapy ;Secondary Objective: - To assess PFS from time of starting first line therapy<br>- To evaluate the Response rate (RECIST version 1.1)<br>- To evaluate the safety profile<br>- To study the relationship between the levels of proangiogenic cytokines and progression (only in selected qualified centers);Primary end point(s): Assessment of efficacy through:<br>- PFS of treatment beyond progression therapy<br>- PFS from time of starting first-line therapy<br>- Overall Response rate (RECIST)<br><br>Assessment of safety through:<br>incidence of serious and non-serious adverse events will be investigated. The NCI CTCAE criteria (version 3.0) will be used to score intensity of these events
- Secondary Outcome Measures
Name Time Method