Vascular Endothelial Growth Factor (VEGF) Imaging Before and During Everolimus Treatment for Renal Cell Carcinoma (Everolimage)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01028638
Recruitment Status : Completed
First Posted : December 9, 2009
Last Update Posted : January 28, 2015
Information provided by (Responsible Party):
S.F. Oosting, University Medical Centre Groningen

Brief Summary:

Everolimus indirectly inhibits angiogenesis by reducing VEGF production. VEGF can be non-invasively visualized and quantified with serial 89Zr-bevacizumab PET imaging in patients.

The investigators hypothesize that a decline in VEGF early during everolimus treatment in patients with metastatic renal cell carcinoma predicts treatment efficacy.

89Zr-bevacizumab PET scans will be performed at baseline, after 2 and 6 weeks of everolimus treatment in 14 adult patients with metastatic renal cell carcinoma.

Condition or disease Intervention/treatment
Metastatic Renal Cell Carcinoma Other: 89Zr-bevacizumab PET scan

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Detailed Description:

Background of the study

The majority of renal cell carcinomas (RCC) is characterized by profound angiogenesis because of inactivation of the Von Hippel Lindau gene. Angiogenesis inhibitors are established first line treatment options in the metastatic setting. Patients with progressive disease during or after treatment with angiogenesis inhibitors can benefit from treatment with everolimus, an oral mTOR inhibitor that resulted in doubling of progression free survival in a phase III study. Currently it is not possible to predict which patient will benefit from treatment with mTOR inhibitors. A predictive biomarker for efficacy of mTOR inhibitors is urgently needed as it may spare the patients unnecessary side effects, safes costs for the society as mTOR inhibitors are very expensive agents, and may speed up research on new drugs, drug combinations and drug dosing. One of the actions of mTOR inhibitors is blockage of production of vascular endothelial growth factor (VEGF), and this is thought to be the primary mechanism that is responsible for antitumor activity in RCC. The investigators hypothesize that non-invasive measurement of VEGF in the tumour and its surroundings by 89Zr-bevacizumab PET imaging before and shortly after start of everolimus is a good readout of efficacy of everolimus in patients with RCC.

Objective of the study

The primary objective of the study is to evaluate the feasibility of 89Zr-bevacizumab PET imaging as a biomarker before and during treatment with everolimus in patients with metastatic RCC. 89Zr-bevacizumab PET imaging will be regarded a promising biomarker if uptake changes after institution of treatment.

Study design

This is a pilot study for evaluation of 89Zr-bevacizumab PET imaging as a biomarker during treatment with everolimus in patients with mRCC.

89Zr-bevacizumab PET imaging will be performed before start of treatment and after 2 and 6 weeks of treatment.

Study population

14 patients who will start treatment with everolimus for metastatic RCC will be included in this study.

Primary study parameters

The primary endpoint is change in 89Zr-bevacizumab uptake in tumor lesions between the baseline scan and the scan during treatment.

Secondary study parameters The secondary endpoint is progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, after 3 months of treatment. Progression is defined as the appearance of new disease or an increase of 20% in the sum of the longest diameters of the target lesions.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness

Patients will be intravenously injected at 3 time points with 37MBq resulting in a cumulative radiation dose of 54 mSv. According to ICRP 62 this radiation dose falls in category III (moderate risk).

Life expectancy of the patients is limited because of their incurable renal cell carcinoma, making the risk of development of a secondary malignancy clinically likely not relevant.

Patients have to pay 3 extra visits to the hospital for tracer injection. PET scans will be performed on regular visit days. Blood samples for biomarkers will be drawn during routine blood investigations.

There is no direct benefit for the patients in this study. If 89Zr-bevacizumab PET imaging however is a predictive biomarker for angiogenesis inhibitors, many patients can be spared unnecessary side effects and society can be spared costs of futile treatment in the future.

Study Type : Observational
Actual Enrollment : 13 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: 89Zr-bevacizumab PET Imaging in Patients With Renal Cell Carcinoma Treated With Everolimus; a Pilot Study
Study Start Date : December 2009
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Group/Cohort Intervention/treatment
Renal Cancer
Renal Cancer patients treated with everolimus
Other: 89Zr-bevacizumab PET scan

A tracer dose of 89Zr-bevacizumab (37 MBq, 5 mg protein dose) is given intravenously at day -3, day 11 and day 39.

PET scans are made on day 1, day 15 and day 43.

Other Name: VEGF imaging

Primary Outcome Measures :
  1. Change in 89Zr-bevacizumab uptake in tumor lesions between the baseline scan and the scan during treatment [ Time Frame: Baseline, 2 weeks and 6 weeks ]

Secondary Outcome Measures :
  1. Progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, after 3 months of treatment [ Time Frame: 3 months ]

Biospecimen Retention:   Samples With DNA
whole blood, white blood cells, plasma, serum, urine

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adult patients with metastatic renal cell carcinoma who will start treatment with everolimus.

Inclusion Criteria:

  • metastatic renal cell cancer
  • Intention to start treatment with everolimus
  • WHO performance score ≤ 2
  • measurable disease with x-ray or CT scan, at least one site of disease must be unidimensionally measurable as follows: X-ray > 20 mm Spiral CT scan > 10 mm Non-spiral CT scan > 20 mm
  • ≥ 18 years
  • not pregnant or nursing
  • women of childbearing potential must use effective contraception
  • absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • before patient randomization, written informed consent must be given according to GCP, and local regulations

Exclusion Criteria:

  • formulated as "not" or "absence of" under inclusion criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01028638

University Medical Centre Groningen
Groningen, Netherlands, 9700 RB
Sponsors and Collaborators
University Medical Center Groningen
Principal Investigator: Sjoukje Oosting, MD University Medical Center Groningen

Responsible Party: S.F. Oosting, Principal investigator, University Medical Centre Groningen Identifier: NCT01028638     History of Changes
Other Study ID Numbers: NL28799.042.09
First Posted: December 9, 2009    Key Record Dates
Last Update Posted: January 28, 2015
Last Verified: January 2015

Keywords provided by S.F. Oosting, University Medical Centre Groningen:
VEGF imaging
renal cell carcinoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Endothelial Growth Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents