Molecular Determinants for Therapy Response on Renal Cell Carcinoma (MORE)

Aim of the scientific analysis is to find biological factors (biomarkers) allowing a prediction of disease progression and a better choice of therapy. After diagnosis the kidney and the tumor will be removed by standard surgery followed by drug therapy. Within surgery remaining tumor tissue will be used for the scientific analysis. In case of disease progression during the drug treatment the drug therapy will be changed. Before therapy change a small tissue sample will be collected for molecular diagnostics. This will be done by puncture through the skin under local anesthesia. Blood samples taken before surgery and at the time of first and second disease progression will also be used for molecular-biological analysis. As there is no clear recommendation for drug therapy after disease progression this study should serve to determine an individual therapy on the basis of the molecular profile and the molecular changes. As the tumor disease changes and developes resistance to drugs, analysis at the time of disease progression shall identify biological factors which will predict a likelihood response to a specific drugs.

This shall allow to give the patient an individual therapy.

Study Overview

• Status: Unknown
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: Sunitinib, Pazopanib, Bevacizumab, Everolimus...

Detailed Description

Aim of this study is to perform a profound molecular analysis of the tumor before beginning therapy and after failure of the approved targeted first-and second line therapy (standard therapy). The tumor sample will be analyzed by using profound molecular analysis to identify target structures which will predict the efficacy of a specific therapy (substance group)and therefore have a predictive value. The analysis of molecular biomarkers include the genomic sequencing of targeted areas or of the entire DNA of the tumor tissue comparative to the DNA of healthy cells, the measurement of DNA-regulatory elements (methylation, mi-RNA expression, protein expression analytics, functional tumorcell analysis in-vitro, efficacy analysis in cell culture or in animal model) who are supposed to inspect the biological influence of the molecular biomarkers and measurements of free tumor DNA out of the blood.

The response to the established standard therapy in the first and second line will be acquired due to all clinical and radiological established standard parameters. The clinical-radiological response will be correlated with the molecular changes and their changes in therapy process to allow predictive prognosis for a further therapy.

There is no approved clinical standard for third line therapy. However there are further medications approved without any scientific evidence of their efficacy in this therapy situation (third line treatment after failure of first and second line treatment) and for which a response of under 6 weeks is expected.

For these patients the third line therapy will be adjusted to the molecular profiles of the previous therapies. Therefore the oncological history of the noticed marker profiles and the presence of target structures (from whom it is known that they are influenced by certain substances) will be considered.

The therapy will use substances which are approved in general for the treatment of metastatic renal cell cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 4
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sascha Pahernik, PD Dr.; Phone Number: +49 6221 5639689; Email: sascha.pahernik@med.uni-heidelberg.de
• Study Contact Backup: Name: Carsten Grüllich, PD Dr.; Phone Number: +49 6221 5637125; Email: carsten.gruellich@med.uni-heidelberg.de

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • Urological Department of the University Hospital Heidelberg
    • Contact: Sascha Pahernik, PD Dr.; Phone Number: +49 6221 56 39689; Email: sascha.pahernik@med.uni-heidelberg.de
    • Principal Investigator: Sascha Pahernik, PD Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Minimum Age: 18 Years Maximum Age: no maximum age

• metastatic lesions easy of access for puncture for specimen storage
• histological subtype: clear-cell renal cancer
• no contraindications against systemic therapy
• indication for systemic therapy given

Exclusion Criteria:

• preexisting mental illness
• further active malignancy
• patients with increased risk of bleeding and/or wound healing disorder
• patients who are not legally competent or unable to consent
• contraindication for surgical intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

No Intervention: Receptor-Tyrosinkinase-Inhibitor; Guidelines-oriented therapy with approved systemic medications for renal cell carcinoma individually for each patient (Receptor-Tyrosinkinase-Inhibitor) (e.g.Sunitinib, Pazopanib, Bevacizumab, Everolimus, Axitinib, Temsirolimus). With 1.progression turning to second line treatment with one of the upper mentioned medications. Third line therapy due to the individual molecular modifications for each patient.

Drug: Sunitinib, Pazopanib, Bevacizumab, Everolimus...; Clinical standard; Other Names: e.g.Sunitinib, Pazopanib, Bevacizumab, Everolimus...

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to disease progression in third line therapy	Progression free survival in third-line therapy ( defined as the time from beginning of the third-line therapy to the date of the first documented progression as determined by the investigator using Response Evaluation Criteria in Solid Tumors criteria assessed by CT/MRI every 12 weeks).	Approximately 2 years depending on when the failure in third line therapy happens

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of preventive biomarkers.	Identification of preventive biomarkers.	2weeks in average before surgery and 4 weeks in average after surgery before starting first line treatment

Other Outcome Measures

Outcome Measure	Time Frame
Identification of preventive biomarkers	2years

Collaborators and Investigators

• Sponsor: Heidelberg University
• Investigators: Principal Investigator: Sascha Pahernil, PD Dr., University of Heidelberg, Urological Department

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Anticipated): February 1, 2018
• Study Completion (Anticipated): February 1, 2018

Study Registration Dates

• First Submitted: June 2, 2014
• First Submitted That Met QC Criteria: July 31, 2014
• First Posted (Estimate): August 4, 2014

Study Record Updates

• Last Update Posted (Estimate): August 4, 2014
• Last Update Submitted That Met QC Criteria: July 31, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Biomarkers; Renal cell carcinoma; Molecular modifications
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib; Bevacizumab; Everolimus
• Other Study ID Numbers: S-539/2013; DRKS00006193 (Other Identifier: Deutsches Register Klinischer Studien)