Neuroendocrine TumorsNETPETNCT01338090
89Zr-bevacizumab PET Imaging in Patients With Neuroendocrine Tumors
An observational study of Neuroendocrine Tumors, run by University Medical Center Groningen at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neuroendocrine Tumors
- What is being tested?
- 89Zr-bevacizumab and Everolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 14 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2010to Mar 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with metastatic neuroendocrine tumors.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 89Zr-bevacizumab PET Imaging as Predictive Biomarker for Everolimus Efficacy in Patients With Neuroendocrine Tumors
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.
Read the detailed description
- 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.
- 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.
- Conditions
- Neuroendocrine Tumors
- Being tested
- 89Zr-bevacizumab, Everolimus
- Keywords
- VEGF imaging, neuroendocrine tumors, biomarker, mTOR inhibition
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
89Zr-bevacizumabDrug
Intravenous injection 120 MBq
EverolimusDrug
Also called RAD001
Oral use, 10 mg per day
| Study group | Role | What they receive |
|---|---|---|
| 89Zr-bevacizumab | Not described Receives: Drug: 89Zr-bevacizumab; Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in 89Zr-bevacizumab uptake
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.
Measured: 12 weeks
Secondary outcomes (1)
Progressive disease
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2011 (estimated)
- Study startApr 2010
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Investigators
- Elisabeth GE de Vries, MD, PHD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01338090
- Sponsor's protocol ID
- 20091104
- Other IDs
- 2009-017195-24, 2009
- Acronym
- NETPET
- Status last verified
- Aug 2011
- First submitted
- 12 Apr 2011
- Last updated
- 3 Apr 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 89Zr-bevacizumab PET Imaging as Predictive Biomarker for Everolimus Efficacy in Patients With Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT01338090
- Acronym / sponsor ID
- NETPET / 20091104
- Conditions
- Neuroendocrine Tumors
- Keywords
- VEGF imaging, neuroendocrine tumors, biomarker, mTOR inhibition
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Apr 2010
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 19 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- 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.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 89Zr-bevacizumab | – | Drug: 89Zr-bevacizumab, Drug: Everolimus |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with metastatic neuroendocrine tumors.
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 89Zr-bevacizumabIntravenous injection 120 MBq | Drug | 89Zr-bevacizumab |
| EverolimusAlso: RAD001Oral use, 10 mg per day | Drug | 89Zr-bevacizumab |
Primary outcome
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.
1 secondary outcome
Progressive disease
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2012.
Related trials for Neuroendocrine Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 3
Somatostatin Analogues vs. Observation After Peptide Receptor Radionuclide Therapy (PRRT) in Nonfunctional Neuroendocrine Neoplasms
Neuroendocrine Neoplasm, Gastroenteropancreatic Neuroendocrine Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elisabeth GE de Vries, MD, PHD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neuroendocrine Tumors, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in 89Zr-bevacizumab uptake (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2012.