Metastatic Colorectal Cancer
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of Irinotecan in combination with FOLFOX+Bevacizumab versus FOLFOX+Bevacizumab alone in the first-line treatment of patients with metastatic colorectal cancer.
Detailed description
5-Fluorouracil and oxaliplatin (FOLFOX-Regimen) in combination with bevacizumab is regarded as standard first-line treatment in metastatic colorectal cancer \[Saltz et al., 2008\]. Current studies established the role of the FOLFOXIRI regimen \[Souglakos et al., 2006, Falcone et al., 2007\]. A further intensification of the therapy seems feasible yielding response rates up to 84% and a disease control rate up to 100% \[Falcone, 2008, Santomaggio, 2009, Masi, 2010\]. This trial evaluates the activity of an intensified first-line therapy for metastatic colorectal cancer compared to standard treatment.
Interventions
DRUGOxaliplatin, 5FU/LV, Bevacizumab
bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/ m2 iv over 48 hours (day 1-3)
DRUG5FU/LV, Oxaliplatin, Bevacizumab, Irinotecan
bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) irinotecan at a dose of 165 mg/m2 iv over two hours (day 1) oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/ m2 iv over 48 hours (day 1-3)
Sponsors
Roche Pharma AG
Martin-Luther-Universität Halle-Wittenberg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer (primary tumor may be present) 2. Patients with at least one measurable lesion, with size \> 1 cm (RECIST v1.1) 3. ECOG Performance status ≤ 2 (ECOG 2, only if tumor related) 4. Patients, who are able to tolerate intensive first lien treatment as judged by the investigator 5. Life expectancy \> 3 months 6. Age ≥ 18 years 7. Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x109/L, hemoglobin * 9 g/dl or 5.59 mmol/l 8. Patients not receiving therapeutic anticoagulation must have an INR \< 1.5 ULN and aPTT \< 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of registration. 9. Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 2.5 x ULN (in case of liver metastases \< 5 x ULN) and total bilirubin ≤ 1.5 x ULN 10. Adequate renal function: Serum creatinine ≤ 1.5 x ULN 11. Signed, written informed consent
Exclusion criteria
1. Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer (primary tumor may be present) 2. Patients with at least one measurable lesion, with size \> 1 cm (RECIST v1.1) 3. ECOG Performance status ≤ 2 (ECOG 2, only if tumor related) 4. Patients, who are able to tolerate intensive first lien treatment as judged by the investigator 5. Life expectancy \> 3 months 6. Age ≥ 18 years 7. Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x109/L, hemoglobin * 9 g/dl or 5.59 mmol/l 8. Patients not receiving therapeutic anticoagulation must have an INR \< 1.5 ULN and aPTT \< 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of registration. 9. Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 2.5 x ULN (in case of liver metastases \< 5 x ULN) and total bilirubin ≤ 1.5 x ULN 10. Adequate renal function: Serum creatinine ≤ 1.5 x ULN 11. Signed, written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| progression free survival rate | 9 months after first study drug administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary resection rate | for a maximum of two years after end of treatment | — |
| Progression free survival rate | until progression of disease for a maximum of two years after end of treatment | — |
| tumour response according to RECIST v 1.1 | until progression of disease for a maximum of two years after end of treatment | — |
| Adverse events | 18 months after the date of last study drug administration | Toxicity of study medication |
| Quality of Life evaluated by questionnaire | Until end of treatment (maximum 2 years after first study drug administration) | Quality of Life evaluated using questionnaire EORTC QLQ-30 |
| Overall survival | until death for a maximum of two years after end of treatment | — |
Countries
Germany
Outcome results
None listed