Ignite Creation Date:
2024-05-06 @ 12:38 AM
Last Modification Date:
2024-10-26 @ 10:52 AM
Study NCT ID:
NCT01622764
Status:
WITHDRAWN
Last Update Posted:
2024-05-06
First Post:
2012-06-15
Brief Title:
89Zr-RO5323441 PET Imaging in Glioblastoma
Sponsor:
University Medical Center Groningen
Organization:
University Medical Center Groningen
Study Overview
Official Title:
89Zr-RO5323441 PET Imaging in Patients With Recurrent Glioblastoma Treated With Bevacizumab
Status:
WITHDRAWN
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
No funding from the sponsor
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The research the investigators propose is a molecular imaging study of RO5323441 an antibody against placental growth factor PlGF in patients with recurrent GBM treated with bevacizumab a drug against vascular endothelial growth factor VEGF Both VEGF and PlGF are molecules involved in tumor growth since they enable the development of tumor vasculature thus delivery of oxygen and nutrients to the tumor The treatment will consist of bevacizumab iv given every 2 weeks until the patient has clinical benefit no disease progression or unacceptable toxicity Meanwhile patients will receive and injection of low protein-dose radiolabeled RO5323441 89Zr-RO5323441 on day -3 and 11 of the first bevacizumab treatment cycle Brain-only 89Zr-RO5323441 positron emission tomography PET will be performed at 2 hours after each injection of 89Zr-RO5323441 on day -3 and 11 Whole body 89Zr-RO5323441 PET will be performed on day 1 and 15 before and after the first treatment with bevacizumab The main purpose of this trial is to determine how much of RO5323441 actually gets into the recurrent GBM lesions since for a drug to be active it has to be able to reach cancer cells As second aims RO5323441 accumulation in normal non-tumor organs will be assessed as well as how bevacizumab influences RO5323441 penetration into tumor lesions to answer the question of combined bevacizumab RO5323441 treatment in GBM or RO5323441 biodistribution in non-tumor organs
Detailed Description:
Rationale Glioblastomas GBM account for 70 of all gliomas 80 of all malignant brain and CNS tumors and remain the most aggressive sub-type of glioma with a particularly poor prognosis Surgery aimed to complete resection is the first therapeutic modality however the infiltrative nature of the disease makes a complete resection nearly impossible In a randomized phase III EORTC-NCIC trial overall survival in newly diagnosed glioblastoma patients treated with concomitant temozolomide and radiotherapy followed by 6 cycles of temozolomide was 272 95 CI 222-325 at 2 years 160 120-206 at 3 years 121 85-164 at 4 years and 98 64-140 at 5 years treatment which is now standard of care Almost all GBM patients experience relapse and there is no one generally agreed standard of care in recurrent GBM Vascular endothelial growth factor-A VEGF-A a central regulator of physiological and pathological angiogenesis is considered to play a major angiogenic role in GBM Bevacizumab a humanized monoclonal antibody against VEGF-A showed a 28RRa 43 6-month PFS and provided a consistent clinical benefit in terms of both delayed progression and increased median overall survival over historical controls This benefit is limited however with the tumor eventually evading treatment by for example compensatory upregulation of angiogenic factors like placental growth factor PlGF Therefore targeting PlGF could be a new strategy of tumor angiogenesis inhibition complementary to VEGFR inhibition In preclinical setting inhibiting PlGF has shown to inhibit growth and metastasis of various tumors Humanized monoclonal PlGF antibody RO5323441 was evaluated in phase I trials in healthy volunteers and in cancer patients no Dose Limiting Toxicity DLT was found thus no Maximum Tolerated Dose MTD defined Stable disease was observed in 623 patients on different dose levels A phase III study of bevacizumab in combination with RO5323441 is currently ongoing in patients with recurrent GBM NCT01308684 However the amount of RO5323441 to reach the recurrent GBM and how this is affected by bevacizumab treatment are yet unknown This can be determined by repetitive measurement of RO5323441 tumor uptake with 89Zr-RO5323441 PET
Objectives The objectives of this study are to assess the penetration of RO532441 into recurrent GBM by 89Zr-RO5323441 PET imaging and to quantify its uptake to visualize and quantify 89Zr-RO5323441 non-tumor organ distribution and to measure the effect of bevacizumab treatment on 89Zr-RO5323441 uptake in recurrent GBM
Study design This is a single center investigator driven 89Zr-RO5323441 PET imaging and bio-distribution study in patients with recurrent GBM treated with bevacizumab Bevacizumab at a dose of 10 mgkg body weight iv in 90 min on day 1 is given every 2 weeks in cycles of 6 weeks The treatment with bevacizumab will continue until documented disease progression unacceptable toxicity patient refusal or patients best interest 89Zr-RO5323441 will be administered iv at a tracer dose of 5 mg 37 MBq on day -3 and on day 11 of cycle 1 of bevacizumab treatment Four PET scans will be performed 2 brain only PET scans and 2 whole body PET scans Brain only PET scans will be performed 2 hours after each 89Zr-RO5323441 administration on day -3 and day 11 and will take 10 minutes scan Whole body PET scans will be performed 4 days after each 89Zr-RO5323441 administration before dosing with bevacizumab on day 1 and day 15 and will take 50 minutes scan 89Zr-RO5323441 uptake values in recurrent GBM lesions at baseline and day 15 will be compared to assess bevacizumab effect on tracer tumor uptake The purpose of the two early brain-only PET scans after each 89Zr-RO5323441 injection is to identify whether changes in 89Zr-RO5323441 uptake in recurrent GBM lesions following treatment with bevacizumab can be solely attributed to an effect on blood volume vascular permeability or rather indicate a possible modulation of placental growth factor PlGF level in the tumor tissue The rationale for the whole body 89Zr-RO5323441 PET scans is to assess 89Zr-RO5323441 non-tumor organs distribution at baseline as well as to evaluate the influence bevacizumab treatment could exert on 89Zr-RO5323441 non-tumor organs uptake For 89Zr-RO5323441 pharmacokinetics blood samples will be taken 1 hour after 89Zr-RO5323441 tracer injection on d-3 and d11 respectively together with the blood samples for hematology on d1 and d15 during the 1st cycle of bevacizumab treatment The rationale for this is that performing both the 89Zr-RO5323441 PET scan data quantification and the assessment of the tracers blood pharmacokinetics would enable us to better understand the specificity of 89Zr-RO5323441 uptake in recurrent GBM lesions Patients will be assessed for bevacizumab treatment response by brain MRI every 6 weeks ie every cycle in the first 6 month and every 12 weeks thereafter until documented progression using the updated RANO criteria Treatment and tracer injection related side effects will be assessed according to the National Cancer Institute NCI Common Terminology Criteria for Adverse Events CTCAE version 40 for toxicity and adverse event reporting
Main study parameters endpoints 89Zr-RO5323441 tumor uptake and organ distribution will be scored visually and quantitatively Standardized uptake value SUV and relative uptake value RUV will be determined and compared in the recurrent GBM lesions and in relevant tissues at baseline and day 15
Nature and extent of the burden and risk associated with participation benefit and group relatedness Bevacizumab is registered in The Netherlands for use in metastasized colon and breast cancer in lung cancer and in advanced renal cell carcinoma and has already been tested in GBM clinical trials Bevacizumab is expected to have clinical benefit for patients enrolled in this study and similar safety profile compared to the other indications RO5323441 monotherapy was well tolerated in patients with advanced malignant diseases In this study one patient will receive a low total protein dose of 10 mg RO5323441 2X5mg in the tracer and it is expected that RO5323441 will not enhance bevacizumab related side effects The total radiation dose of 89Zr-RO5323441 for a patient participating in this study would be 36 mSv for women and 30 mSv for men According to the investigators this radiation burden is justifiable in this patient group by the information that can be obtained in this study Risk exposure to 89Zr-RO5323441 PET scan-related radiation possibility of allergic reaction to the protein in the tracer possible side-effects of bevacizumab
Objectives The objectives of this study are to assess the penetration of RO532441 into recurrent GBM by 89Zr-RO5323441 PET imaging and to quantify its uptake to visualize and quantify 89Zr-RO5323441 non-tumor organ distribution and to measure the effect of bevacizumab treatment on 89Zr-RO5323441 uptake in recurrent GBM
Study design This is a single center investigator driven 89Zr-RO5323441 PET imaging and bio-distribution study in patients with recurrent GBM treated with bevacizumab Bevacizumab at a dose of 10 mgkg body weight iv in 90 min on day 1 is given every 2 weeks in cycles of 6 weeks The treatment with bevacizumab will continue until documented disease progression unacceptable toxicity patient refusal or patients best interest 89Zr-RO5323441 will be administered iv at a tracer dose of 5 mg 37 MBq on day -3 and on day 11 of cycle 1 of bevacizumab treatment Four PET scans will be performed 2 brain only PET scans and 2 whole body PET scans Brain only PET scans will be performed 2 hours after each 89Zr-RO5323441 administration on day -3 and day 11 and will take 10 minutes scan Whole body PET scans will be performed 4 days after each 89Zr-RO5323441 administration before dosing with bevacizumab on day 1 and day 15 and will take 50 minutes scan 89Zr-RO5323441 uptake values in recurrent GBM lesions at baseline and day 15 will be compared to assess bevacizumab effect on tracer tumor uptake The purpose of the two early brain-only PET scans after each 89Zr-RO5323441 injection is to identify whether changes in 89Zr-RO5323441 uptake in recurrent GBM lesions following treatment with bevacizumab can be solely attributed to an effect on blood volume vascular permeability or rather indicate a possible modulation of placental growth factor PlGF level in the tumor tissue The rationale for the whole body 89Zr-RO5323441 PET scans is to assess 89Zr-RO5323441 non-tumor organs distribution at baseline as well as to evaluate the influence bevacizumab treatment could exert on 89Zr-RO5323441 non-tumor organs uptake For 89Zr-RO5323441 pharmacokinetics blood samples will be taken 1 hour after 89Zr-RO5323441 tracer injection on d-3 and d11 respectively together with the blood samples for hematology on d1 and d15 during the 1st cycle of bevacizumab treatment The rationale for this is that performing both the 89Zr-RO5323441 PET scan data quantification and the assessment of the tracers blood pharmacokinetics would enable us to better understand the specificity of 89Zr-RO5323441 uptake in recurrent GBM lesions Patients will be assessed for bevacizumab treatment response by brain MRI every 6 weeks ie every cycle in the first 6 month and every 12 weeks thereafter until documented progression using the updated RANO criteria Treatment and tracer injection related side effects will be assessed according to the National Cancer Institute NCI Common Terminology Criteria for Adverse Events CTCAE version 40 for toxicity and adverse event reporting
Main study parameters endpoints 89Zr-RO5323441 tumor uptake and organ distribution will be scored visually and quantitatively Standardized uptake value SUV and relative uptake value RUV will be determined and compared in the recurrent GBM lesions and in relevant tissues at baseline and day 15
Nature and extent of the burden and risk associated with participation benefit and group relatedness Bevacizumab is registered in The Netherlands for use in metastasized colon and breast cancer in lung cancer and in advanced renal cell carcinoma and has already been tested in GBM clinical trials Bevacizumab is expected to have clinical benefit for patients enrolled in this study and similar safety profile compared to the other indications RO5323441 monotherapy was well tolerated in patients with advanced malignant diseases In this study one patient will receive a low total protein dose of 10 mg RO5323441 2X5mg in the tracer and it is expected that RO5323441 will not enhance bevacizumab related side effects The total radiation dose of 89Zr-RO5323441 for a patient participating in this study would be 36 mSv for women and 30 mSv for men According to the investigators this radiation burden is justifiable in this patient group by the information that can be obtained in this study Risk exposure to 89Zr-RO5323441 PET scan-related radiation possibility of allergic reaction to the protein in the tracer possible side-effects of bevacizumab
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2011-004974-27 | EUDRACT_NUMBER | None | None |