ANGIOPREDICT. ICORG 12-16, V3

Exploratory Phase II Clinical Trial Comprising Biomarker Analysis of Oxaliplatin Plus Fluorouracil/Leucovorin (FOLFOX) in Combination With Bevacizumab (Bvz) in First Line Treatment of Metastatic Colorectal Cancer (CRC) Expressing Mutant K-ras - AC-ANGIOPREDICT

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.

Study Overview

• Status: Completed
• Conditions: Advanced Colorectal Cancer
• Intervention / Treatment: Other: Biomarker analysis

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).

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany
    • Medizinische Klinik III, Universitaetsklinikum
  • Deggendorf, Germany
    • Onkologisches Zentrum
  • Homburg, Germany
    • University Hospital Saarland
  • Lebach, Germany
    • Gemeinschaftspraxis Haematologie/Onkologie
  • Ludwigsburg, Germany
    • Kilnikum Ludwigsburg
  • Mainz, Germany
    • Medizinische Klinik and Poliklinik Mainz
  • Mannheim, Germany
    • Univeritaetsmedizin Mannheim
  • Rhineland-Palatinate
    • Speyer, Rhineland-Palatinate, Germany
      • Private Practice Oncology
• Ireland
  • Cork, Ireland
    • Bon Secours Hospital
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland
    • Beaumont Hospital
  • Dublin, Ireland
    • St James Hospital
  • Dublin, Ireland, D4
    • St Vincent's University Hospital
  • Dublin, Ireland
    • The Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
  • Galway, Ireland
    • Galway University Hospital
  • Sligo, Ireland
    • Sligo General Hospital
  • Waterford, Ireland
    • Waterford Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intent-to-treat population with aCRC or mCRC; Advanced Colorectal Cancer with planned treatment with a aCRC or mCRC and who fulfil all inclusion and exclusion criteria	Other: Biomarker analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of biomarkers	Identification of biomarkers, which are predictive for response and/or prolonged PFS to FOLFOX/bvz combination therapy in aCRC or mCRC patients.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of identified biomarkers	Validation of identified biomarkers with regard to response rate/failure to further treatment strategy, PFS, overall survival (OS) and toxicity.	4 years

Collaborators and Investigators

• Sponsor: Cancer Trials Ireland

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: February 25, 2013
• First Submitted That Met QC Criteria: March 27, 2013
• First Posted (Estimated): April 2, 2013

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Rectal Cancer; Colon Cancer; Metastatic Colorectal Cancer; Advanced Colorectal Cancer; Locally Advanced Colorectal Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Rectal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: ICORG 12-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED