Profile of Soluble and Cellular Biomarkers and of Functional Imaging During Antiangiogenic Therapies in Cancer Patients

Tumour angiogenesis has been identified to play a critical role in tumour growth and this knowledge has led to the identification of new targets for cancer therapy. Multiple angiogenic factors are involved in the regulation of angiogenesis, among them VEGF (vascular endothelial growth factor) and its receptor are of crucial relevance. The inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully established for the treatment of different cancer entities and multiple new drugs are being tested in clinical trials. The ever-expanding list of antiangiogenic agents being available in the near future will raise the questions when to use which agent and in which sequence. As a consequence biomarkers are going to be indispensible tools for choosing the most effective drugs and to predict dosing and resistance.

The present project is based on an academic clinical trial in which patients suffering from different cancer types (colorectal cancer, non-small cell lung cancer, renal cell cancer and hepatocellular cancer) treated routinely with antiangiogenic agents will be included. Consecutive serum and blood probes will be taken and will be examined and correlated with functional imaging and the clinical course. The following parameters have been selected: soluble markers in the plasma (VEGF, bFGF, ICAM, sVGFR-2 IL-8, SDF1 and Dickkopf 3) and cellular parameters like circulating endothelial cells (CEC) and circulating endothelial progenitor cells (CEPs).

In conclusion, the present project is screening for potential biomarkers and biomarker combinations relevant for antiangiogenic drugs in different tumour types. The predictive value of such profiles should then be evaluated in larger cohorts. In the future such profiles could possibly help clinicians to use these agents more effectively and therefore also more economically.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Non-small Cell Lung Cancer; Renal Cell Cancer; Hepatocellular Cancer
• Intervention / Treatment: Drug: Avastin; Drug: Suntent; Drug: Nexavar

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, A-6020
    • University Hospital Innsbruck, Internal Medicine V, Hematology Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• 10 NSCLC patients treated with bevacizumab monotherapy (maintenance therapy)
• 10 RCC patients treated either with sorafenib or sunitinib monotherapy
• 10 CRC patients treated with bevacizumab monotherapy
• 10 HCC patients treated with sorafenib monotherapy

Description

Inclusion Criteria:

• Age over 18 years
• Patients with HCC, NSCLC, RCC or CRC treated with an approved antiangiogenic drug (bevacizumab, sorafenib, sunitinib)*
• Patients with at least one measurable lesion. Lesions must be measurable by CT-scan or MRI (Magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumours (RECIST)

Exclusion Criteria:

• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
• Known or suspected allergy to the investigational agent or any agent given in association with this trial -_> allergy
• MRI contraindications: implants (pacemaker)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Control group n=20
2; investigational group (cancer patients) n=40 patients treated with antiangiogenic agent	Drug: Avastin; Dosage, duration, indications and contraindications of treatment rely on the sole responsibility of the treating physician and are not subject of the present study; Drug: Suntent; Dosage, duration, indications and contraindications of treatment rely on the sole responsibility of the treating physician and are not subject of the present study; Drug: Nexavar; Dosage, duration, indications and contraindications of treatment rely on the sole responsibility of the treating physician and are not subject of the present study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival under antiangiogenic therapy	From date of study inclusion until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	progression of disease, up to 48 months

Collaborators and Investigators

• Sponsor: Medical University Innsbruck
• Investigators: Principal Investigator: Wolfgang Hilbe, Prof, Medical University Innsbruck

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: September 18, 2009
• First Submitted That Met QC Criteria: January 8, 2012
• First Posted (Estimate): January 11, 2012

Study Record Updates

• Last Update Posted (Estimate): April 29, 2015
• Last Update Submitted That Met QC Criteria: April 28, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma, Hepatocellular; Liver Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sorafenib; Bevacizumab
• Other Study ID Numbers: Praemarker AAT 08