Advanced Colorectal Cancer
Conditions
Keywords
Colorectal Cancer, Advanced Colorectal Cancer, Metastatic Colorectal Cancer, Locally Advanced Colorectal Cancer, Colon Cancer, Rectal Cancer
Brief summary
Primary Objective: The primary objective is to validate previously identified predictive/prognostic genomic DNA and expression biomarkers of response to combination bvz treatments in K-ras mutant advanced CRC (a CRC) or metastatic CRC (mCRC). Secondary Objective: 1. To test the efficacy of bvz in combination with FOLFOX in patients with newly diagnosed advanced or metastatic K-ras mutant CRC and 2. To determine the progression free and overall survival of patients under first line FOLFOX + bvz in aCRC or mCRC.
Detailed description
Study Design: Type of Study: Exploratory, translational, multicenter and multinational Phase II study. Patient Population:All patients from the intent-to-treat population with aCRC or mCRC, (incurable with any conventional multimodality approach) and who fulfil all inclusion and exclusion criteria. Number of Patients: 224 Sample Type: Serial tissue and blood samples will be collected before (week 0), during (week 6, month 3 and 6) and at the end of treatment (month 12).
Interventions
OTHERBiomarker analysis
Sponsors
Cancer Trials Ireland
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients ≥ 18 years of age. 2. Patients diagnosed with recurrent or de novo, locally advanced (unresectable) or metastatic adenocarcinoma of the colon or rectum. 3. Planned combination bevacizumab (bvz) treatment with either: * leucovorin, fluorouracil and oxaliplatin (FOLFOX) * capecitabine and oxaliplatin (XELOX) * leucovorin, fluorouracil and irinotecan (FOLFIRI) * capecitabine and irinotecan (XELIRI) 4. Naive for bvz 5. An evaluable site of disease 6. ECOG Performance status 0, 1, or 2 7. Adequate renal function as shown by serum creatinine ≤ 1.5 x ULN or GFR ≥ 50ml/min 8. Adequate hematopoietic function \[white blood cell (WBC) count ≥ 3000/μl, absolute neutrophil count (ANC) ≥1500/μl, platelets ≥100 000/μl, haemoglobin level ≥ 9.0 g/dl\] 9. Adequate end organ function, defined as the following: total bilirubin \< 1.5 x ULN, SGOT and SGPT \< 3.0 x ULN (in case of liver metastases SGOT and SGPT \< 5.0 x ULN) 10. Ability to give signed informed consent prior to any screening procedures 11. FFPE Tissue is available
Exclusion criteria
1. Patient has received any other investigational product within 28 days of first day of study drug dosing 2. Patients having familial and/or hereditary CRC 3. CRC associated with ulcerative colitis 4. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of biomarkers | 4 years | Identification of biomarkers, which are predictive for response and/or prolonged PFS to FOLFOX/bvz combination therapy in aCRC or mCRC patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Validation of identified biomarkers | 4 years | Validation of identified biomarkers with regard to response rate/failure to further treatment strategy, PFS, overall survival (OS) and toxicity. |
Countries
Germany, Ireland
Outcome results
None listed