Status and phase
Conditions
Treatments
About
Major attempt is being given to the potential of curing patients with metastatic colorectal cancer due to the recognition of dramatic change in survival figures achieved in palliative chemotherapy combination treatment protocols. Achieving resectablity rates in previously unresectable patients has been defined as study endpoint among other well known primary and secondary objectives. Curing metastatic colorectal cancer is most likely in resectable patients and therefore the logical next step after completion of chemotherapy combination studies (e.g. EORTC 40983) is the addition of targeted agents. Bevacizumab has the most valid data of improving outcome figures and was therefore chosen as additional agent. Safety of the combination with Xelox was demonstrated in the investigators pilot trial (Gruenberger JCO 2006, ASCO 2006, WCGC 2006, ESMO 2006), consequently response rate and resection rate will be the primary endpoints in this trial.
STUDY OBJECTIVES
Primary Objective The primary objective of this study is the Resectability (R0) rate after neoadjuvant Bevacizumab in potentially resectable mCRC.
Secondary Objectives The secondary objectives of this study include
STUDY DURATION Recruitment is planned for 12 months. Patients will be treated for 6 cycles XELOX and 5 cycles Bevacizumab. Surgery will be performed 2 weeks after the last Capecitabine administration, allowing a time window of 5 weeks between the last Bevacizumab administration and surgery.
Therapy with 6 cycles of XELOX and Bevacizumab will be restarted 4-5 weeks after surgery.
With a Follow up period of 2 years after the last enrolled patient, in order to assess RFS and OS, the trial will last for approx. 3 years.
NUMBER OF CENTRES Four centres with a high level of experience in the surgery of liver metastases are planned to participate in this study.
SELECTION CRITERIA
Total Number of Patients and Target Population The planned total sample size for this study is 43 patients. Patients with potentially resectable metastatic colorectal cancer previously untreated for metastatic disease will be enrolled in this trial.
Full description
Major attempt is being given to the potential of curing patients with metastatic colorectal cancer due to the recognition of dramatic change in survival figures achieved in palliative chemotherapy combination treatment protocols. Achieving resectablity rates in previously unresectable patients has been defined as study endpoint among other well known primary and secondary objectives. Curing metastatic colorectal cancer is most likely in resectable patients and therefore the logical next step after completion of chemotherapy combination studies (e.g. EORTC 40983) is the addition of targeted agents. Bevacizumab has the most valid data of improving outcome figures and was therefore chosen as additional agent. Safety of the combination with Xelox was demonstrated in our pilot trial (Gruenberger JCO 2006, ASCO 2006, WCGC 2006, ESMO 2006), consequently response rate and resection rate will be the primary endpoints in this trial.
STUDY OBJECTIVES
Primary Objective The primary objective of this study is the Resectability (R0) rate after neoadjuvant Bevacizumab in potentially resectable mCRC.
Secondary Objectives The secondary objectives of this study include
STUDY DURATION Recruitment is planned for 12 months. Patients will be treated for 6 cycles XELOX and 5 cycles Bevacizumab. Surgery will be performed 2 weeks after the last Capecitabine administration, allowing a time window of 5 weeks between the last Bevacizumab administration and surgery.
Therapy with 6 cycles of XELOX and Bevacizumab will be restarted 4-5 weeks after surgery.
With a Follow up period of 2 years after the last enrolled patient, in order to assess RFS and OS, the trial will last for approx. 3 years.
NUMBER OF CENTRES Four centres with a high level of experience in the surgery of liver metastases are planned to participate in this study.
SELECTION CRITERIA
Total Number of Patients and Target Population The planned total sample size for this study is 40 patients. Patients with potentially resectable metastatic colorectal cancer previously untreated for metastatic disease will be enrolled in this trial.
STUDY DESIGN
Design This is a single arm, multicenter Phase I/II trial to evaluate the Resectability (R0) rate after neoadjuvant Bevacizumab in combination with a biweekly regime of capecitabine plus oxaliplatin (XELOX) in potentially resectable mCRC.
The pre-operative treatment phase consists of 6 cycles XELOX and 5 cycles Bevacizumab. The cycle duration is 2 weeks.
Surgery will be performed 2 weeks after the last administration of Capecitabine, allowing a time window of 5 weeks between the last dose of Bevacizumab and surgery.
The post-operative treatment phase consists of 6 cycles XELOX + Bevacizumab and will be re-started 4-5 weeks after surgery.
Patients will be further followed for tumour progression and survival for a further 2 years after the last patient has been enrolled in this trial (end of the study follow up).
Schedule of Assessment and Study Procedures Study assessments and procedures will be performed as shown in Table 1 and 2. Screening and Baseline Written informed consent must be obtained prior to the patient undergoing any study-specific procedures.
If a Central Venous Access Device (CVAD) is required, at least a 2-day interval between placement of a central line and first bevacizumab administration is recommended.
Treatment Phase (pre- and post-operative) Standard Clinical Assessments
Laboratory Assessments
The following laboratory tests are to be done:
Surgery and Control Visits after Surgery
The first control visit should be performed 10 days after surgery and should include the following assessments:
The second control visit will be performed 21 days after surgery and should include the same assessments as on the first control visit with the addition of:
Final Visit End of treatment safety visit to be performed 28 days after the last drug administration.
Follow up Phase and Termination of Study Progression Free Survival Status and Survival status should be assessed every 3 months for a maximum of 2 years.
STUDY MEDICATION
Dose, Schedule and Administration Bevacizumab Bevacizumab will be given at 5 mg/kg on d1 every two weeks, for 5 consecutive cycles. The 6th cycle will be XELOX without Bevacizumab, allowing for a time window between last administration of Bevacizumab and surgery of 5 weeks.
The time window between surgery and re-start of treatment will be at least 4 weeks and wound healing must be completed. Bevacizumab will then be given at 5 mg/kg on d1 every two weeks, for 6 consecutive cycles in combination with XELOX.
Bevacizumab doses will be calculated for each patient in milligrams per kilogram. The patient's actual weight from the screening visit will be the reference weight throughout the study (i.e., patients will receive the same dose at each treatment). Doses of Bevacizumab will be recalculated for patients who experience more than 10% change in body weight from baseline during the treatment period.
All patients will receive an infusion of study drug in a total volume of 100 mL of 0.9% Sodium Chloride Injection, USP. Bevacizumab infusions should not be administered or mixed with dextrose or glucose solutions.
The initial study drug dose will be delivered over 90 minutes as a continuous IV infusion. If the first infusion is tolerated without infusion associated adverse events the second infusion may be delivered over 60 minutes. If the 60 minute infusion is tolerated, all subsequent infusions may be delivered over 30 minutes. If a patient experiences infusion associated adverse events with the 60 minute infusion, all subsequent doses will be given over 90 minutes. If a patient experiences infusion associated adverse events with the 30 minute infusion, all subsequent doses will be given over 60 minutes.
Should extravasation of the study drug infusion occur, the following steps are to be taken:
In the pre-surgery phase, Bevacizumab will be obtained locally by prescription. After surgery, Bevacizumab will be supplied as glass vials with 4-mL fill, containing 100 mg (25 mg/mL) or with 16-mL fill, containing 400 mg (25 mg/mL). Vials contain no preservative and are for single use only.
Oxaliplatin Liquid Oxaliplatin will be given at 85 mg/m2 on d1 every two weeks, for 6 consecutive cycles, before and after surgery.
Liquid Oxaliplatin dose will be calculated using the body surface area (BSA) of the patient (see Appendix 2). The dose of oxaliplatin administered should be as close as possible to the calculated dose.
Liquid Oxaliplatin administration does not require hyperhydration. In the event of extravasation, administration must be discontinued immediately.
For nausea and vomiting, 5-HT3 antagonists with or without dexamethasone are strongly recommended for oxaliplatin-based chemotherapy.
Liquid Oxaliplatin must be infused either by peripheral vein or central venous line over 2 hours. The infusion line must be adequately flushed with 5% dextrose solution (D5W) between oxaliplatin infusion and the administration of any other drug.
Liquid Oxaliplatin (Eloxatin®) will be obtained locally by prescription.
Capecitabine The dose of Capecitabine is 1.500 mg/m2 twice daily from the evening of d1 until the morning of d8, followed by 1 week rest period. One treatment cycle consists of 2 weeks. Capecitabine will be given for 6 consecutive cycles, before and after surgery.
The appropriate daily dose of capecitabine is identified by determination of the Body Surface Area (see Appendix 2 and 3).
Capecitabine is to be administered orally within 30 minutes after the end of a meal (breakfast, dinner). Tablets should be swallowed with approximately 200 mL water (not fruit juices). The first dose of each cycle will be administered as the evening dose on day 1 and the last dose of each cycle is scheduled the morning of day 8, followed by a 7 day rest period.
Capecitabine (Xeloda®) will be obtained locally by prescription.
Study Treatment Duration In the pre-operative treatment phase 6 cycles of XELOX and 5 cycles of Bevacizumab will be administered, resulting in a total treatment duration of 12 weeks.
Surgery will be performed 2 weeks after the last administration of Capecitabine.
Post-operative treatment consists of 6 cycles XELOX + Bevacizumab and will re-start 4-5 weeks after surgery.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria:
Exclusion Criteria
Primary purpose
Allocation
Interventional model
Masking
43 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal