Study of Bevacizumab in Combination With Alternating Xeliri and Xelox in Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Open-label, single-arm, phase II study of bevacizumab (AvastinTM) in combination with alternating Xeliri and Xelox as first-line treatment of patients with metastatic colorectal cancer. Primary objective: PFS, To assess overall resectability in patients with metastatic colorectal cancer, postoperative morbidity and outcomes after resection. Secondary objectives: To assess response rates according to RECIST criteria, failure free survival (TTF) and overall survival (OS), Quality of life according to 15D questionnaire, To radiologically assess tumour density and morphology, and assess alternative radiologic response evaluation in comparison with RECIST response criteria, Biomarker evaluation to measure plasma biomarkers, tumour blocks and DNA polymorphisms that may predict drug effects, safety, resectability and clinical behaviour of the tumour

Official Title
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Phase 2 Study of Bevacizumab in Combination With Alternating Xeliri and Xelox as First-line Treatment of Patients With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Bevacizumab plus alternating Xelox/Xeliri


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed diagnosis of CRC, chemotherapy naïve for metastatic disease (prior adjuvant chemotherapy more than 6 months previously for CRC allowed), who are scheduled to start first line chemotherapy for metastatic disease Age > 18 Measurable or evaluable metastatic disease Performance status ECOG performance status 0-2 Life expectancy greater than 3 months Normal Thrombocytes, neutrophils, Aspartate amino transferase/Alanine amino transferase, Alkaline phosphatase, Serum bilirubin, Serum Creatinine, Urine dipstick of proteinuria. Women of childbearing potential must have a negative serum pregnancy test done prior to the administration of bevacizumab. Patient and their partner should have adequate contraception up to at least 6 months after last treatment completion or the last drug dose, whatever happens first Signed written informed consent according to ICH/GCP and the local regulations (approved by the Independent Ethics Committee [IEC]) will be obtained prior to any study specific screening procedures Patient must be able to comply with the protocol Exclusion Criteria: Prior treatment with first-line chemotherapy for metastatic CRC Adjuvant treatment within 6 months Major surgical procedure (placing of central venous access device and liver biopsy etc are considered minor procedure), open biopsy or significant traumatic injury within 28 days prior to Day 0 (Patients must have recovered from any major surgery) Near future planned radiotherapy for underlying disease (prior completed radiotherapy treatment allowed) Clinical or radiological evidence of CNS metastases Past or current history within the last 2 years of malignancies except for the indication under this study and curatively treated basal and squamous cell carcinoma of the skin or in-situ carcinoma of the cervix Serious non-healing wound or ulcer Evidence of bleeding diathesis or coagulopathy Uncontrolled hypertension 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 Treatment with any investigational drug within 30 days prior to enrolment Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the treatment or patient at high risk from treatment complications Chronic daily intake of aspirin (> 325 mg/day) or clopidogren (> 75 mg/day) Pregnancy (positive serum pregnancy test) and lactation Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy plus bevazicumab<br> | Drug: Bevacizumab plus alternating Xelox/Xeliri<br>* 3 cycles of XELOX+bevacizumab alternating with 3 cycles XELIRI+bevacizumab until disease progression<br>* Other names: oxaliplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resectability | To assess overall resectability in patients with metastatic colorectal cancer, postoperative morbidity and outcomes after resection | 5 years | 
| Efficacy | progression free survival | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | To assess response rates according to RECIST criteria | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic colorectal cancer