Colorectal cancer with initially unresectable liver metastases MedDRA version: 16.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Avastin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Bevacizunab
CAS Number: 216974-75-3
Current Sponsor code: RO4876646
Other descriptive name: rhuMAb V
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically confirmed carcinoma of the colon and/or rectum with evidence of liver metastases. - Male and female patients aged greater than or equal to 18 years. - ECOG performance score of 0 or 1. - Written informed consent. - General condition considered feasible for major abdominal surgery after first line treatment. - Unresectability of hepatic metastases at randomisation (at least one of the following criteria): - No upfront R0 / R1 resection of all hepatic lesions possible Note: a patient with bilobar disease suitable for a two-stage resection would still fulfil the inclusion criteria for unresectability. - Less than 30% estimated residual liver after resection - Disease in contact with major vessels of the remnant live (vessels remaining after potential hepatectomy) 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - Evidence of extrahepatic metastatic disease (excluded by FDG-PET). - Evidence of diffuse peritoneal carcinosis or involvement of celiac lymph nodes. - Prior systemic or local treatment of metastatic disease. - Prior adjuvant or neo-adjuvant chemotherapy for primary tumour completed less than 6 months prior to randomisation (Note: in case of synchronous metastatic rectal cancer, chemotherapy/radiotherapy for primary tumour is allowed within 6 months of randomisation). - Treatment with any other investigational agent within 30 days prior to randomisation or participation in another clinical trial while participating in this clinical trial. - Current or recent (within 10 days of randomization) chronic use of aspirin (> 325 mg/day) or clopidrogel (> 75 mg/day). - 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 randomization) 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). - Clinically significant cardiovascular disease, for example CVA, myocardial infarction (less than or equal to 12 months before randomization), unstable angina, New York Heart Association (NYHA) greater than or equal to Class II, congestive heart failure (CHF), arrhythmia requiring medication, or uncontrolled hypertension. - Evidence of bleeding diathesis or coagulopathy. - Known hypersensitivity to any of the study drugs. - Serious, non-healing wound, ulcer or bone fracture. - Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization. - 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. - Life expectancy less than 3 months. - Inability or unwillingness to comply with the protocol. - Inadequate haematological function: ANC 1.5 within 7 days prior to randomization. aPTT >1.5 x ULN within 7 days prior to randomization. - Liver function: Serum bilirubin > 1.5 x ULN; alkaline phosphatase and transaminases > 5 x ULN (liver metastases). - Serum Creatinine > 1.5 x ULN. - Urine dipstick for proteinuria grater than or equal to 2+. If urine dipstick is greater than or equal to 2+, 24-hour urine must demonstrate less than or equal to 1 g of protein in 24 hours for patient to be eligible. - Pregnancy or lactation. - Positive serum pregnancy test within 7 days of randomization in pre-menopausal women and women < 2 years after the onset of menopause. Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded. - Fertile women (< 2 years after last menstruation) and men of childbearing potential unwilling or unable to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Overall resection rate (R0 / R1 / R2);Secondary Objective: - Histopathological response (assessment of viable tumour cells within the resected specimen) - Relapse-free survival (RFS) - Progression-free survival (PFS) - Overall survival (OS) - Overall response rate (ORR) - Time to response (TTR) - Surgical safety ;Primary end point(s): The overall incidence of achieved R0/R1/R2 resections in patients rendered resectable after/during pre-operative chemotherapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary study endpoints include assessment of the following parameters after pre-operative/post-operative treatment with bevacizumab and chemotherapy: - Histopathological response - Relapse-free survival - Progression-free survival - Overall survival - Overall response rate (ORR) - Time to response;Timepoint(s) of evaluation of this end point: 3 years after LPLV | — |
Countries
Austria, France, Spain, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed