Clinical trial NCT02119026
Conditions: Metastatic Colorectal Cancer
Keywords: metastatic colorectal cancer Patients with metastatic colorectal cancer who did not receive systemic treatment for their metastatic disease
Sponsor: Prof. Dr. Werner Scheithauer
Start date: 2011-02-01; Completion date: 2017-08-31
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
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.

Detailed description:

Arms: arm 1: capecitabine and irinotecan (XELIRI) plus bevacizumab (AVASTIN; BEV)

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. arm 2: capecitabine and oxaliplatin (XELOX) plus bevacizumab (Avastin; BEV)

Arm B:

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.
Interventions: intervention 1: Capecitabine intervention 2: Capecitabine intervention 3: Bevacizumab intervention 4: Oxaliplatin intervention 5: Irinotecan
Intervention descriptions: intervention 1: 800mg/m2 bid d1-14

± 1000 mg/m2 bid,days 1-14 q3w: maintenance intervention 2: 1000mg/m2 bid d1-14, intervention 3: 7,5 mg/kg given on d1 q3w intervention 4: 130mg/m2 iv. d 1 q3w intervention 5: 200mg/m2 iv. d 1 q3w .

Protocol documents:
Prot_SAP_000.pdf: