Metastatic colorectal cancer MedDRA version: 16.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: ZALTRAP
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: aflibercept
CAS Number: 862111-32-8
Current Sponsor code: AVE0005
Other descriptive name: AFLIBERCEP
Sponsors
Hellenic Cooperative Oncology Group
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. Metastatic disease confirmed clinically/radiologically, 4. No prior therapy for metastatic disease 5. Duly documented inoperable metastatic disease, ie not suitable for complete curative surgical resection, 6. At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1 7. Age =18 years, 8. ECOG Performance status (PS) 0-2, 9. Adequate hematological status: neutrophils (ANC) =1.5x109/L; platelets =100x109/L; haemoglobin =9g/dL, 10. Adequate renal function: serum creatinine level =1.5 mg/dl and Glomelular Filtration Rate>50 ml/min by Cockroft/Gault formula, 11. Adequate liver function: serum bilirubin =1.5 x upper normal limit (ULN), alkaline phosphatase, AST, ALT =65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: 1. Exclusive presence of bone metastasis only, 2. Uncontrolled hypercalcemia, 3. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg despite medical therapy), or history of hypertensive crisis, or hypertensive encephalopathy, 4. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy), 5. Treatment with any other investigational medicinal product within 28 days prior to study entry, 6. Other serious and uncontrolled chronic non-malignant disease, 7. History or presence of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizures not controlled with standard medical therapy) 8. Gilbert’s syndrome, 9. Intolerance to atropine sulfate or loperamide 10. Known dihydropyrimidine dehydrogenase deficiency 11. Treatment with CYP3A4 inducers unless discontinued > 7 days prior to randomization 12. Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis. 13. 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, 14. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days 15. Pregnant or breastfeeding women, 16. Patients with known allergy to any excipients to study drugs, 17. History of myocardial infarction and/or stroke or other arterial thrombotic events or pulmonary embolism or unstable angina pectoris within 6 months prior to registration, 18. Poorly controlled cardiac arrhythmias 19. Bowel obstruction 20. History of severe tumour bleeding or bleeding disorders 21. Poorly controlled anti-coagulation therapy (INR>3.0 on coumadin or heparin compounds) 22. Palliative radiation therapy within 4 weeks prior to registration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the 12-month progression-free survival (PFS) rate ;Secondary Objective: • To evaluate the efficacy of the combination in terms of overall response rate (ORR), overall survival (OS) and progression-free survival (PFS). • To evaluate the safety of the combination • To investigate potential biomarkers for benefit from treatment combination, in the context of translational research. • To investigate pharmacokinetics/pharmacodynamics of the combination;Primary end point(s): Assessment of Progression-Free Survival (PFS) rate at 1 year;Timepoint(s) of evaluation of this end point: 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Imaging studies will be performed every 8 weeks from treatment initiation for the first year and every 12 weeks thereafter 2. Overall survival is defined as the time interval from registration to the date of death due to any cause. 3. PFS is defined as the time interval from registration to the first date of documented progression or death due to any cause. 4. Assessment of Adverse Events will be performed in every cycle throughout the treatment 5. At study initiation 6. At study initiation, on cycles 1 and 3, during maintenance treatment and at disease progression;Secondary end point(s): 1. Evaluation of objective response rate (ORR) 2. Evaluation of overall survival (OS) 3. Evaluation of progression-free survival (PFS) 4. Evaluation of safety 5. Study of potential biomarkers (Translational research) 6. Pharmacokinetic/pharmacodynamic analysis | — |
Countries
Greece
Contacts
Public ContactClinical Trials
Hellenic Cooperative Oncology Group
Outcome results
None listed