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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University Medical Centre Groningen
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
S.F. Oosting, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01028638
First received: December 8, 2009
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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 Intervention
Metastatic Renal Cell Carcinoma
Other: 89Zr-bevacizumab PET scan

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: 89Zr-bevacizumab PET Imaging in Patients With Renal Cell Carcinoma Treated With Everolimus; a Pilot Study

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, after 3 months of treatment [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

whole blood, white blood cells, plasma, serum, urine


Estimated Enrollment: 14
Study Start Date: December 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Adult patients with metastatic renal cell carcinoma who will start treatment with everolimus.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01028638

Contacts
Contact: Sjoukje Oosting, MD + 31 50 3612821 s.oosting@umcg.nl
Contact: Jourik Gietema, MD PhD +31 50 3612821 j.a.gietema@umcg.nl

Locations
Netherlands
University Medical Centre Groningen Recruiting
Groningen, Netherlands, 9700 RB
Principal Investigator: Sjoukje Oosting, MD         
Sponsors and Collaborators
University Medical Centre Groningen
Novartis
Investigators
Principal Investigator: Sjoukje Oosting, MD University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: S.F. Oosting, Principal investigator, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01028638     History of Changes
Other Study ID Numbers: NL28799.042.09, METc2009.236
Study First Received: December 8, 2009
Last Updated: May 22, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by University Medical Centre Groningen:
VEGF imaging
everolimus
renal cell carcinoma
PET
bevacizumab

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

ClinicalTrials.gov processed this record on July 22, 2014