Clinical trial NCT01531595: Study of Bevacizumab in Combination with Alternating XELIRI and XELOX in Metastatic Colorectal Cancer
Official title: Phase 2 Study of Bevacizumab in Combination with Alternating XELIRI and XELOX As First-line Treatment of Patients with Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: metastatic colorectal cancer
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
First posted: 2012-02-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: * Open-label, single-arm, phase II study of bevacizumab (AvastinTM) in combination with alternating XELIRI (capecitabine+irinotecan) and XELOX (capecitabine+oxaliplatin) as first-line treatment of patients with metastatic colorectal cancer.
* Primary objective: Progression Free Survival (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 15-dimensional instrument (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


Eligibility criteria: Inclusion Criteria:

1. Patients with histologically confirmed diagnosis of colorectal cancer (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
2. Age \> 18
3. Measurable or evaluable metastatic disease
4. Performance status Eastern co-operative oncology group (ECOG) performance status 0-2
5. Life expectancy greater than 3 months
6. Normal Thrombocytes, neutrophils, Aspartate amino transferase/Alanine amino transferase, Alkaline phosphatase, Serum bilirubin, Serum Creatinine, Urine dipstick of proteinuria.
7. 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
8. Signed written informed consent according to international council for harmonization (ICH)/Good clinical practice (GCP) and the local regulations (approved by the Independent Ethics Committee (IEC)) will be obtained prior to any study specific screening procedures
9. Patient must be able to comply with the protocol

Exclusion Criteria:

1. Prior treatment with first-line chemotherapy for metastatic CRC
2. Adjuvant treatment within 6 months
3. 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)
4. Near future planned radiotherapy for underlying disease (prior completed radiotherapy treatment allowed)
5. Clinical or radiological evidence of central nervous system (CNS) metastases
6. 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
7. Serious non-healing wound or ulcer
8. Evidence of bleeding diathesis or coagulopathy
9. Uncontrolled hypertension
10. 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
11. Treatment with any investigational drug within 30 days prior to enrolment
12. 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
13. Chronic daily intake of aspirin (\> 325 mg/day) or clopidogrel (\> 75 mg/day)
14. Pregnancy (positive serum pregnancy test) and lactation
15. Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial

Primary outcomes:
measure: Resectability of metastases
timeFrame: 5 years
measure: Efficacy of alternating therapy
timeFrame: 5 years
Secondary outcomes:
measure: Response of alternating therapy
timeFrame: 5 years
measure: Efficacy of treatment
timeFrame: 5 years
measure: Progression-free survival
timeFrame: 5 years
measure: Translational research
timeFrame: 10 years
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Department of Oncology
Study officials:
affiliation: Helsinki University Central Hospital
name: Pia Osterlund, MD
role: PRINCIPAL_INVESTIGATOR
References: