89Zr-RO5323441 PET Imaging in Glioblastoma

NCT01622764 | Withdrawn Phase 2

• 2 other identifiers: BP280152011-004974-27
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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 (i.v.) 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.

Conditions

Glioblastoma

Keywords

RO5323441; bevacizumab; PET imaging; recurrent glioblastoma

Outcome Measures

Primary Outcomes (1)

• Assess the penetration of RO5323441 into recurrent GBM by 89Zr-RO5323441 PET imaging and to quantify its uptake

  Calculations of specific 89Zr-RO5323441 uptake in recurrent GBM lesions will be determined for all patients who underwent tracer injection(s) and 89Zr-RO5323441 PET. 89Zr-RO5323441 tumor uptake will be scored visually and quantitatively. The visual analysis of the PET scans will be performed by a qualified nuclear medicine physician. Quantification of 89Zr-RO5323441 uptake will be performed using AMIDE software (Stanford University, Palo Alto, CA). Standardized uptake value (SUV) and relative uptake value (RUV)of 89Zr-RO5323441 will be determined.

  Patients will be assessed up to 19 days after the first 89Zr-RO5323441 tracer injection (D-3)

Secondary Outcomes (2)

• Visualize and quantify 89Zr-RO5323441 non-tumor organ distribution

  Patients will be assessed up to 19 days after the first 89Zr-RO5323441 tracer injection (D-3)

• Assess the effect of bevacizumab treatment on 89Zr-RO5323441 uptake in recurrent GBM lesions

  Patients will be assessed up to 19 days after the first 89Zr-RO5323441 tracer injection, which also corresponds to the second bevacizumab dose administered

Study Arms (1)

Molecular imaging with 89Zr-RO5323441

EXPERIMENTAL

Radiation: Molecular imaging with 89Zr-RO5323441

Interventions

Molecular imaging with 89Zr-RO5323441 RADIATION

Bevacizumab at a dose of 10 mg/kg body weight i.v. in 90 min on day 1 will be given every 2 weeks in cycles of 6 weeks, until documented disease progression, unacceptable toxicity, patient refusal or patient's best interest. 89Zr-RO5323441 will be administered i.v. 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. Whole body PET scans will be performed 4 days after each 89Zr-RO5323441 administration (before dosing with bevacizumab on day 1 and day 15).

Also known as: TB403

Molecular imaging with 89Zr-RO5323441

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age more or at least equal to 18 years
• WHO Performance Status between 0 and 2
• Histologically proven glioblastoma multiforme at recurrence, including patients with anaplastic oligoastrocytomas with necrosis
• Patients treated with one line of systemic treatment (combined treatment with temozolomide and RT followed by 6 cycles of temozolomide is considered as one line of systemic treatment)
• No prior treatment with bevacizumab or other PlGF,VEGF,VEGF-R targeted agents, cilengitide or enzastaurin
• No radiotherapy within 4 weeks prior to the diagnosis of progression
• No chemotherapy within 4 weeks prior to study enrollment
• Adequate bone marrow function
• Adequate liver function
• Adequate renal function
• Women of reproductive potential, female patients within one year of entering the menopause as well as males must agree to use an effective non-hormonal method of contraception during the treatment period and for at least 6 months after the last dose of bevacizumab
• Written informed consent

You may not qualify if:

• Invasive procedures (major surgical procedure, open biopsy or significant traumatic injury) within 28 days prior to start study treatment, or anticipation of the need for major surgery during the course of the study treatment. Placement of a vascular access device is not considered as a major surgical procedure if performed more than 24 hours prior to bevacizumab administration.
• Arterial or venous thrombosis less or equal than 6 months prior to study registration
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Uncontrolled hypertension defined by a systolic blood pressure (BP) more than 140 mm Hg and or diastolic pressure more than 100 mm Hg, with or without anti-hypertensive medication. Patients with initial blood pressure elevation are eligible if initiation or adjustment of anti-hypertensive medication lowers pressure to meet the entry criteria
• History or evidence of inherited bleeding diathesis or coagulopathy with risk of bleeding
• Current or recent (within 10 days of first dose of bevacizumab) use of aspirin more than 325 mg per day) or other NSAID with anti-platelet activity or treatment with dipyramidole, ticlopidine, clopidogrel and cilostazol
• Use of therapeutic-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes
• Clinically serious (as judged by the investigator) non-healing wounds, active skin ulcers or incompletely healed bone fracture
• Evidence of any active infection requiring hospitalization or antibiotics, within 2 weeks prior to day 1 of cycle 1
• Current or recent (within 4 weeks of enrollment) treatment with another investigational drug or participation in another investigational study
• Known hypersensitivity to any part of the bevacizumab formulation
• Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibody
• Other diseases, interfering with the follow-up
• Geographical, psychological or other non-medical conditions interfering with follow-up
• Pregnant or lactating females (serum pregnancy test to be assessed before entry in the trial)

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Molecular Imaging; TB-403

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Molecular Probe Techniques; Investigative Techniques

Study Officials

• Annemiek M. Walenkamp, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2012
• First Posted: June 19, 2012
• Study Start: September 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2016
• Last Updated: May 6, 2024

Record last verified: 2024-05

Locations

NL (1)