Unresectable Wild-Type KRAS Metastatic Colorectal Cancer MedDRA version: 16.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: bevacizumab
Product Name: bevacizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Concentration unit: mg/ml milligra
Sponsors
GERCOR
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated informed consent, and willing and able to comply with protocol requirements, 2. Histologically proven adenocarcinoma of the colon and/or rectum, 3. Wild-type KRAS tumor (local assessment, performed either on primary tumor or metastasis), 4. Metastatic disease confirmed, 5. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be >6 months for fluoropyrimidine alone or >12 months for oxaliplatin-based, bevacizumab-based, or cetuximab-based therapy), 6. Duly documented unresectable metastatic disease, ie not suitable for complete carcinological surgical resection at inclusion [NB: patients with unresectable disease at study entry but with any potential of salvage surgery after induction therapy are eligible], 7. At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1, 8. Age =18 years, 9. ECOG Performance status (PS) 0-2, 10. Hematological status: neutrophils (ANC) =1.5x109/L; platelets =100x109/L; haemoglobin =9g/dL, 11. Adequate renal function: serum creatinine level =65 years) yes F.1.3.1 Number of subjects for this age range 237
Exclusion criteria
Exclusion criteria: 1. History or evidence upon physical examination of CNS metastasis (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy), unless adequately treated, 2. Exclusive bone metastasis, 3. Uncontrolled hypercalcemia, 4. Pre-existing permanent neuropathy (NCI grade =2), 5. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy, 6. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy), 7. Treatment with any investigational medicinal product within 28 days prior to study entry, 8. Other serious and uncontrolled non-malignant disease, 9. Gilbert’s syndrome, 10. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years, 11. Major surgery (open biopsy, surgical resection, wound revision or any other major surgery involving entry into body cavity) or significant traumatic injury within the last 28 days prior to randomization, and/or minor surgical procedure including placement of a vascular device within 2 days of first study treatment, 12. Pregnant or breastfeeding women, 13. Patients with known allergy/hypersensitivity to any component of study drugs, 14. History of arterial thrombo and/or embolic event (e.g. myocardial infarction, stroke,…) within 6 months prior to randomization, 15. Total bowel obstruction, 16.History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to randomization, 17. Serious, non-healing wound, active ulcer or untreated bone fracture, 18. History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding, 19. Current or recent (within 10 days of randomization) use of aspirin (>325 mg/d), clopidogrel (>75 mg/d) or use of oral anticoagulants or thrombolytic agents.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate two treatment strategies in wild-type KRAS metastatic colorectal cancer patients: (1) FOLFIRI-cetuximab, followed by oxaliplatin-based chemotherapy with bevacizumab vs. (2) OPTIMOX-bevacizumab, followed by irinotecan-based chemotherapy with bevacizumab, followed by anti-EGFR mab with or without irinotecan.;Primary end point(s): duration of disease control (DDC);Timepoint(s) of evaluation of this end point: sum of PFS of each active treatment course planned in the treatment strategy. Assessed at the end of the strategy.;Secondary Objective: - To assess health related Quality of life (EORTC QLQ C-30), - To evaluate Overall Survival (OS), - To evaluate Time to Failure of Strategy (TFS), - To evaluate Progression-free survival (PFS) per sequence of therapy, - To evaluate Duration of disease control (DDC) per drug, - To evaluate tumor Response Rate (RR) per sequence of therapy (RECIST v1.1), - To evaluate curative salvage surgery rate (R0 or R1 resection, global and per sequence of therapy), - To evaluate the safety profile of each treatment sequence (NCI CTCAE v4.0). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: - QoL assessed at baseline and every 2 months during treatment. - OS is defined as the time interval from randomization to the date of death from any cause. Follow-up until death. - TFS is defined as beginning with the initiation of the strategy under investigation and ending with the first of the predefined events - PFS is defined as the time interval from randomization to the date of first documented disease progression or death from any cause - Tumor response will be assessed using RECIST version 1.1. at baseline and every 2 months during treatment. - AEs assessed at each cycle;Secondary end point(s): - Time to QoL score deterioration for targeted dimensions - Overall survival (OS) - Time to failure of strategy (TFS) - Progression-free survival (PFS) - Tumor response - Salvage surgery - safety | — |
Countries
Austria, Belgium, France, Ireland, Israel, Italy, Spain
Contacts
Public ContactGERCOR
GERCOR
Outcome results
None listed