Patients with metastatic colorectal cancer, who have not previously received systemic treatment for metastatic disease. MedDRA version: 12.0 Level: LLT Classification code 10055114 Term: Colon cancer metastatic
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Bevacizumab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Sponsors
CONSORZIO ONCOTECH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically proven diagnosis of colorectal cancer 2. Metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease 3. Age >= 18 4. ECOG Performance Status 0-1 (Appendix III) 5. Life expectancy of at least 12 weeks 6. Measurable and/or evaluable lesions according to RECIST criteria 7. Laboratory requirements: Neutrophils >=1.5 x 10(9)/L and Platelets >=100 x 10(9)/L Total bilirubin 50 mL/min or serum creatinine =2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Radiotherapy to any site within 4 weeks before the study. 2. Prior adjuvant chemotherapy with an oxaliplatin-containing regimen. 3. Symptomatic and/or unstable pre-existing brain metastases. 4. History of inflammatory bowel disease and/or acute/subacute bowel occlusion. 5. Serious non-healing wound or ulcer. 6. Evidence of bleeding diathesis or coagulopathy. 7. Uncontrolled hypertension. 8. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. 9. Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes. 10. Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate toxicity and the safety profile of the combination. To evaluate duration of response (DR), time to progression (TTP), time to treatment failure (TTF), and overall survival (OS).;Main Objective: First step: To determine the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT) and the recommended dose of erlotinib in combination with fixed doses of bevacizumab, capecitabine, and oxaliplatin. Second step: To assess the preliminary antitumor activity in terms of overall response rate (complete and partial responses) of erlotinib in combination with bevacizumab, capecitabine, and oxaliplatin;Primary end point(s): This is a phase I-II study. At each dose level (first step) will be treated a cohort of 3 consecutive patients. In absence of dose- limiting toxicity (DLT) we will proceed to the next dose-level. Each cycle of treatment will be repeated every three weeks and patients are scheduled to receive at least three courses of therapy at the same dose level. Escalation of the dose to the next higher level proceeds after all 3 patients received the first cycle of therapy with the preceding dose and have been observed for at least 21 days without evidence of a dose-limiting toxicity (DLT), as defined below. Drug-related toxicities will be evaluated during each cycle of therapy and graded according to the NCI Common Toxicity Criteria. A DLT is defined as any of the following events: grade 4 neutropenia, grade 4 thrombocytopenia; any drug-related nonhematological toxicity greater than or equal to grade 3 (except alopecia). At the occurrence of a DLT in three patients from any cohort, an additional three patients will be enrolled at the preceding dose level, which is then considered the maximum tolerated dose (MTD) and the recommended dose for further evaluation (second step). | — |
Countries
Italy
Outcome results
None listed