Efficacy And Safety Of Xeliri + Avastin Followed By Xelox + Avastin Or Reverse Sequence In Metastatic Colorectal Cancer (PASSION)
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|ClinicalTrials.gov Identifier: NCT02119026|
Recruitment Status : Unknown
Verified May 2014 by Prof. Dr. Werner Scheithauer, Medical University of Vienna.
Recruitment status was: Recruiting
First Posted : April 21, 2014
Last Update Posted : May 7, 2014
Since its introduction, 5-fluorouracil (5-FU) has been the cornerstone of treatment for metastatic colorectal cancer (mCRC). Meanwhile the oral 5FU pro-drug Capecitabine (Xeloda®) proved equivalence to 5-FU and is a well tolerated alternative combination partner for Irinotecan (XELIRI) or Oxaliplatin (XELOX) which are widely used for first line treatment of mCRC. Recent advances in molecular biology have resulted in the development of an inhibitor of the vascular endothelial growth factor (VEGF) by the monoclonal humanized antibody bevacizumab (Avastin®).
XELOX or XELIRI +bevacizumab have been investigated in several trials, but not in an approach with clearly defined cross-wise XELIRI-XELOX change criteria. This trial investigates two different sequential treatment options with XELIRI/ XELOX in first and second line with the addition of bevacizumab and tries to give answer to the question if there is an optimal sequence for the benefit of the patient.
This is a prospective, randomized, open-label, 2-arm pilot trial in patients with mCRC who did not receive systemic treatment for their metastatic disease. The study is designed to evaluate the efficacy of XELIRI followed by XELOX and XELOX followed by XELIRI + bevacizumab in terms of Duration of Disease Control (DDC).
Patients will be treated with an established first line therapy consisting of either XELOX or XELIRI + bevacizumab. The chemotherapy treatment will be given for 6 months except prior disease progression, unacceptable toxicity or patient refusal. Bevacizumab will be given until disease progression, unacceptable toxicity or patient refusal.
Capecitabine can be given in addition at the investigators' discretion until disease progression, unacceptable toxicity or patient refusal.
If serious side effects occur despite adequate dose reduction, Oxaliplatin or Irinotecan should be discontinued. In case of Oxaliplatin or Irinotecan-related discontinuation Capecitabine and Bevacizumab should be continued. If Capecitabine also has to be discontinued in first line treatment bevacizumab should be continued. In case of permanent discontinuation of bevacizumab for toxicities, chemotherapy should be continued.
Upon completion of first line chemotherapy patients with disease control will receive bevacizumab maintenance treatment. On investigators decision patients can receive Capecitabine as additional maintenance treatment.
The primary endpoint is to determine the efficacy of a modified XELIRI + bevacizumab followed by XELOX + bevacizumab scheme at progression in comparison with the reverse sequence based on DDC.
Secondary endpoints are first line progression-free survival (PFS), second line PFS, overall response rate, time to response, duration of response, overall survival, tumor assessments (based on RECIST criteria) using CT scans, MRI scans, X-ray, bone scan, clinical examination.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer||Drug: Capecitabine Drug: Bevacizumab Drug: Oxaliplatin Drug: Irinotecan||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study to Assess Efficacy and Safety of Capecitabine and Irinotecan Plus Bevacizumab Followed by Capecitabine and Oxaliplatin Plus Bevacizumab or the Reverse Sequence in Patients With Metastatic Colorectal Cancer|
|Study Start Date :||February 2011|
|Estimated Primary Completion Date :||December 2014|
|Estimated Study Completion Date :||December 2014|
Active Comparator: A
capecitabine and irinotecan (XELIRI) plus bevacizumab (AVASTIN)
Capecitabine : 800mg/m2 bid d1-14, bevacizumab 7,5 mg/kg given on day 1 q3w combined with irinotecan 200mg/m2 iv. d 1 q3w . Bevacizumab (7.5 mg/kg q3w) ± Capecitabine (1000 mg/m2 bid, days 1-14 q3w) maintenance
At disease progression irinotecan will be replaced by oxaliplatin (arm A). Bevacizumab will be continued.
800mg/m2 bid d1-14
± 1000 mg/m2 bid,days 1-14 q3w: maintenance
Other Name: Brand Name: Xeloda
7,5 mg/kg given on d1 q3w
Other Name: Brand name: Avastin
200mg/m2 iv. d 1 q3w .
Active Comparator: B
capecitabine and oxaliplatin (XELOX) plus bevacizumab (Avastin)
Capecitabine: 1000mg/m2 bid d1-14, bevacizumab 7,5 mg/kg given on d1 q3w combined with oxaliplatin 130mg/m2 iv. d 1 q3w Bevacizumab (7.5 mg/kg q3w) ± Capecitabine (1000 mg/m2 bid, days 1-14 q3w) maintenance
At disease progression oxaliplatin will be replaced by irinotecan (arm B). Bevacizumab will be continued.
1000mg/m2 bid d1-14,
Other Name: Brand name: Xeloda
7,5 mg/kg given on d1 q3w
Other Name: Brand name: Avastin
130mg/m2 iv. d 1 q3w
- Efficacy Duration of disease control by tumor assessment (CT/MRI/clinical examination) [ Time Frame: screening, every 8 to 9 weeks until progression, at end of treatment (other than progression), every 3 months until progression, death or up to 24 months (whatever comes first) ]end of treatment could neither be specified for an individual case, since it depends completely on individual response to therapy, nor for the total study population
- first line progression free survival (PFS) [ Time Frame: at progression of disease (PD) in first line therapy or at 28 days safety follow-up in cases without PD ]
- second line PFS [ Time Frame: at progression of disease (PD) in second line therapy or at 28 days safety follow-up in cases without PD ]
- overall response rate [ Time Frame: at the day of documented complete or partial response or at 28 days safety follow-up in cases without PD ]
- time to response [ Time Frame: at the day of documented complete or partial response or at 28 days safety follow-up in cases without PD ]
- duration of response [ Time Frame: at the day of documented complete or partial response or at 28 days safety follow-up in cases without PD ]
- overall survival of XELIRI plus bevacizumab and XELOX plus bevacizumab [ Time Frame: date of death or date of last tumor assessment (28d safety f-u) in patients without death ]
- tumour assessments (based on RECIST criteria) [ Time Frame: Baseline, every 8-9 weeks, 28d Safety follow-up ]for the tumor assessment, CT scans, MRI scans, X-ray, bone scan and clinical examinations are used
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02119026
|Contact: Werner Scheithauer, Prof.Dr.||+43-1-40400 firstname.lastname@example.org|
|Contact: Gabriela Kornek, Prof.Dr.||+43-1-40 400 email@example.com|
|Medical University of Vienna||Recruiting|
|Vienna, Austria, 1090|
|Contact: Werner Scheithauer, Prof. Dr. +43-1-40 400 ext 4424 firstname.lastname@example.org|
|Contact: Gabriela 4424 Kornek, Prof. Dr. +43-1-40 400 email@example.com|
|Principal Investigator: Werner Scheithauer, Prof. Dr.|
|Principal Investigator:||Werner Scheithauer, Prof. Dr.||Medical University of Vienna|