Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of metastases. Diagnosis of metastatic disease according to RECIST not more than 3 months prior to enrolment No prior chemotherapeutic treatment for metastatic colorectal carcinoma MedDRA version: 18.1 Level: LLT Classification code 10010028 Term: Colorectal cancer Duke's D System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal can
Conditions
Interventions
Trade Name: Xeloda
Product Name: Xeloda
Product Code: RO0091978
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Capecitabine
CAS Number: 158798-73-3
Current Sponsor code: RO0091978
Conce
Sponsors
Medizinische Universität Wien, Univ.Klink f. Innere Medizin I
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Written informed consent 2) Age = 18 years 3) Patient must be able to comply with the protocol 4) Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of metastases. 5 )Diagnosis of metastatic disease according to RECIST not more than 3 months prior to enrolment. 6) Life Expectancy of at least 3 months 7) At least one measurable metastatic lesion (as per RECIST criteria) 8) Prior adjuvant or neo-adjuvant chemotherapy /radiotherapy allowed if completed more than 6 months before inclusion. Patients who received Oxaliplatin for neoadjuvant or adjuvant treatment should receive XELIRI for 1st line treatment, patients who received Irinotecan for neoadjuvant or adjuvant treatment should receive XELOX for 1st line treatment for their metastatic disease. 9) ECOG performance score of 0 or 1 10) Adequate haematological function: ANC = 1.5 x 109/L; platelets = 100 x 109/L, Hb = 9 g/dL 11) INR = 1.5 and aPTT = 1.5 x ULN within 7 days prior to starting study treatment 12) Adequate liver function: Serum bilirubin = 1.5 x ULN; alkaline phosphatase and transaminases = 2.5 x ULN (in case of liver metastases =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1) Prior chemotherapeutic treatment for metastatic CRC 2) Symptomatic CNS metastases 3) Significant vascular disease (e.g. aortic aneurysm potentially requiring surgical intervention, pulmonary embolism or recent peripheral arterial thrombosis) within 6 months prior start of study treatment. 4) History of haemoptysis (= ½ teaspoon of bright red blood per episode) within 1 month prior start of study treatment 5) Past or current history (within the last 2 years prior to treatment start) of other malignancies (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible). 6) Clinically significant cardiovascular disease, for example CVA (= 6 months before treatment start), myocardial infarction (= 6 months before treatment start), unstable angina, NYHA = grade 2 CHF, arrhythmia requiring medication, or uncontrolled hypertension. 7) Prior history of hypertensive crisis or hypertensive encephalopathy 8) Treatment with any other investigational agent or any other biological agent (e.g.cetuximab), or participation in another clinical trial within 30 days prior to entering this study. 9) Known hypersensitivity to any of the study drugs 10) Current or recent (within 10 days of first dose of study treatment) chronic use of aspirin (> 325 mg/day) 11) Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes. 12) Evidence of bleeding diathesis or coagulopathy. 13) Serious, non healing wound, ulcer, or bone fracture. 14) Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment, or anticipation of the need for major surgery during the course of the study. If CVAD is required for chemotherapy administration, it should be inserted within 2 days prior to study treatment cycle. 15) Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior start of study therapy 16) History of abdominal fistula, tracheo-oesophageal fistula or any grade 4 non gastrointestinal fistula, gastrointestinal perforation or intraabdominal abscess before 1st line therapy. 17) History or evidence upon physical/neurological examination of CNS disease (unrelated to cancer) (unless adequately treated with standard medical therapy) e.g. uncontrolled seizures 18) Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications 19) Patients with contraindication for cross over chemotherapy (e.g. patients treated with irinotecan based first line therapy and serious polyneuropathy > grade 1, not feasible for oxaliplatin based cross over second line therapy, or patients treated with oxaliplatin based first line therapy and hereditary fructose intolerance not feasible for Irinotecan based cross over second line therapy) 20) Pregnancy or lactation 21) Fertile women (<2 years after last menstruation) and men not willing to use effective means of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the efficacy of modified XELIRI (Capecitabine and Irinotecan) in combination with bevacizumab followed by XELOX (Capecitabine and Oxaliplatin) in combination with bevacizumab at progression in comparison with the reverse sequence based on duration of disease control (DDC) . ;Secondary Objective: -Determine • first line progression free survival (PFS) • second line PFS • overall response rate • time to response • duration of response • overall survival of XELIRI plus bevacizumab and XELOX plus bevacizumab -Tumour assessments (based on RECIST criteria) using CT scans, MRI scans, X-ray, bone scan, clinical examination ;Primary end point(s): The primary endpoint is to determine the efficacy of modified XELIRI (Capecitabine and Irinotecan) in combination with bevacizumab followed by XELOX (Capecitabine and Oxaliplatin) in combination with bevacizumab at progression in comparison with the reverse sequence based on DDC. ;Timepoint(s) of evaluation of this end point: 64 months from first patient entered (first patient in 12-April-2012) (accrual time was 33 months from 1st patient entered, projected analysis of the primary endpoint will be 64 months from first patient entered). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: To determine • first line PFS • second line PFS • the overall response rate • time to response • duration of response • overall survival of Xeliri plus bevacizumab and Xelox plus bevacizumab - Tumour assessments (based on RECIST criteria) using CT scans, MRI scans, X-ray, bone scan, clinical examination. ;Timepoint(s) of evaluation of this end point: 64 months from first patient entered (first patient in 12-April-2012) (accrual time was 33 months from 1st patient entered, projected analysis of the primary endpoint will be 64 months from first patient entered). | — |
Countries
Austria
Contacts
Public ContactUniv.Klink f. Innere Medizin I
Medizinische Universität Wien
Outcome results
None listed