Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 25 of 2732 for:    Neuroendocrine Tumors | Neuroendocrine Tumors

89Zr-bevacizumab PET Imaging in Patients With Neuroendocrine Tumors (NETPET)

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.
ClinicalTrials.gov Identifier: NCT01338090
Recruitment Status : Completed
First Posted : April 19, 2011
Last Update Posted : April 3, 2012
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by:
University Medical Center Groningen

Brief Summary:

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

Patients with progressive disease during the last year will receive treatment with everolimus 10 mg/day orally and 89Zr-bevacizumab PET imaging will be performed before start of treatment and after 2 and 12 weeks of treatment in the first three patients. If the scan after 2 weeks of treatment is already informative further patients will not undergo a scan at 12 weeks. A scan is considered already informative if both scans show at least 30% decrease in uptake in case of response, or at least 30% increase in uptake in case of disease progression.

Four days before the scan patients will be injected intravenously 37 MBq, protein dose 5 mg 89Zr-bevacizumab. At day 1, day 15 and day 99, PET images will be made for visualization and quantification of VEGF in the tumor lesions and blood will be drawn for determination of angiogenesis and mTOR pathway related biomarkers.


Condition or disease Intervention/treatment
Neuroendocrine Tumors Drug: 89Zr-bevacizumab Drug: Everolimus

Detailed Description:
  1. Rationale:

    Profound angiogenesis is an important characteristic of neuroendocrine tumors. Antiangiogenic drugs including sunitinib, bevacizumab and everolimus have shown antitumor activity in neuroendocrine tumors. The investigators participated in the RAD001 studies for neuroendocrine tumors. From preclinical studies including studies performed in our own lab the investigators know that everolimus downregulates VEGF.

    Currently it is not possible to predict which individual patient will benefit from treatment with an mTOR inhibitor. A predictive biomarker for efficacy of mTOR inhibitors is urgently needed and would be helpful, as a predictive biomarker may facilitate the development of combination therapies, of individual titration of the dose, and it may facilitate early clinical studies. Furthermore, it may spare the patients unnecessary side effects. mTOR inhibitors may fail in individual patients because angiogenesis is not sufficiently inhibited. Non-invasive imaging of VEGF before and early after start of treatment may have predictive value for treatment efficacy.

    Within the UMCG the investigators have an active ongoing research line on molecular imaging. The investigators have developed as part of this the 89Zr-bevacizumab PET label for non-invasive measurement of VEGF levels in the tumor and its surrounding microenvironment. This tracer can give insight in the tumors' dependency on angiogenesis as the investigators have already proven for a VEGF-receptor tyrosine kinase inhibitor. Currently this tracer is used in clinical trials. The investigators would like to examine whether all neuroendocrine tumors produce VEGF and whether they differ in their response to inhibition of VEGF by mTOR.

  2. Objectives:

The primary objective is to evaluate the feasibility of 89Zr-bevacizumab-PET imaging as predictive biomarker before and during treatment with everolimus in patients with neuroendocrine tumors.

The secondary Objectives are the following:

  • To explore if 89Zr-bevacizumab PET imaging can differentiate patients with progressive neuroendocrine tumors from patients with non-progressive disease early during treatment with everolimus.
  • To explore relationships between VEGF pathway related blood biomarkers and changes in 89Zr-bevacizumab tumor uptake.

Layout table for study information
Study Type : Observational
Actual Enrollment : 14 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: 89Zr-bevacizumab PET Imaging as Predictive Biomarker for Everolimus Efficacy in Patients With Neuroendocrine Tumors
Study Start Date : April 2010
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012


Group/Cohort Intervention/treatment
89Zr-bevacizumab Drug: 89Zr-bevacizumab
Intravenous injection 120 MBq

Drug: Everolimus
Oral use, 10 mg per day
Other Name: RAD001




Primary Outcome Measures :
  1. change in 89Zr-bevacizumab uptake [ Time Frame: 12 weeks ]
    The change in 89Zr-bevacizumab uptake in tumor lesions between the baseline PET scan and the scans performed after 2 and 12 weeks of everolimus treatment in patients with neuroendocrine tumors. In addition, effect sizes and confidence intervals will be determined.


Secondary Outcome Measures :
  1. Progressive disease [ Time Frame: 12 weeks ]

    Progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST)22 criteria on CT after 12 weeks 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.




Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with metastatic neuroendocrine tumors.
Criteria

Inclusion Criteria:

  • adult patients with metastatic neuroendocrine tumors
  • radiological documentation of progressive disease over the past year
  • measurable disease according to RECIST criteria
  • Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb > 9 g/dL.
  • Adequate liver function: serum bilirubin: ≤ 1.5 x ULN, ALT and AST ≤ 2.5x ULN. Patients with known liver metastases: AST and ALT ≤ 5x ULN.
  • Adequate renal function: serum creatinine ≤ 1.5 x ULN.
  • Fasting serum cholesterol ≤300 mg/dL OR 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In cases where one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication

Exclusion Criteria:

  • uncontrolled medical conditions (eg, unstable angina, symptomatic heart failure, serious intercurrent infections)
  • any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule of the study
  • Patients with uncontrolled diabetes mellitus as defined by fast blood sugar > 1.5 x ULN.
  • Prior therapy with RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus).
  • Concomitant medications known to inhibit, induce or be a substrate to isoenzyme CYP3A are excluded unless the drugs are medically necessary and no substitutes are available. If there are no acceptable substitutes, special precautions should be taken in these patients

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 ClinicalTrials.gov identifier (NCT number): NCT01338090


Locations
Layout table for location information
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Sponsors and Collaborators
University Medical Center Groningen
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Principal Investigator: Elisabeth GE de Vries, MD, PHD University Medical Center Groningen

Layout table for additonal information
Responsible Party: Prof.dr. E.G.E. de Vries, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT01338090     History of Changes
Other Study ID Numbers: 20091104
2009-017195-24 ( EudraCT Number )
First Posted: April 19, 2011    Key Record Dates
Last Update Posted: April 3, 2012
Last Verified: August 2011

Keywords provided by University Medical Center Groningen:
VEGF imaging
neuroendocrine tumors
biomarker
mTOR inhibition

Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Bevacizumab
Everolimus
Sirolimus
89Zr-bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action