Clinical Trial · NCT01622764

89Zr-RO5323441 PET Imaging in Glioblastoma

Overview

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.

Sponsor

University Medical Center Groningen

Phase

Phase 2

Contacts

Annemiek M. Walenkamp, MD, PhD (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT01622764

Eligibility

Inclusion

No prior treatment with bevacizumab or other PlGF,VEGF,VEGF-R targeted agents, cilengitide or enzastaurin
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)
Adequate liver function
No radiotherapy within 4 weeks prior to the diagnosis of progression
No chemotherapy within 4 weeks prior to study enrollment
WHO Performance Status between 0 and 2
Adequate bone marrow 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

Exclusion

Arterial or venous thrombosis less or equal than 6 months prior to study registration
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
Current or recent (within 4 weeks of enrollment) treatment with another investigational drug or participation in another investigational study
History of myocardial infarction (less or equal than 6 months prior to inclusion), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring digoxin treatment
Prior history of hypertensive crisis or hypertensive encephalopathy
Clinically serious (as judged by the investigator) non-healing wounds, active skin ulcers or incompletely healed bone fracture
Known hypersensitivity to any part of the bevacizumab formulation
Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibody
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
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.
Other diseases, interfering with the follow-up
Pregnant or lactating females (serum pregnancy test to be assessed before entry in the trial)
Evidence of any active infection requiring hospitalization or antibiotics, within 2 weeks prior to day 1 of cycle 1
Use of therapeutic-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes
Geographical, psychological or other non-medical conditions interfering with follow-up
History or evidence of inherited bleeding diathesis or coagulopathy with risk of bleeding