Clinical Trial · NCT01999270

Evaluation of FDOPA-PET/MRI in Pediatric Patients With CNS Tumors

Overview

To determine if FDOPA-PET/MRI imaging can predict response to treatment of bevacizumab.

Sponsor

Washington University School of Medicine

Phase

Phase 1

Contacts

Karen Gauvain, M.D. (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT01999270

Drug / Compound

DOPA

Isotope(s):

Target(s):

AADC

Ligand Class: Small Molecules

Eligibility

Inclusion

Patient must have fully recovered from the acute toxic effects of all prior chemotherapy or radiation prior to entering this study.
Urine protein should be screened by dipstick analysis. If protein ≥ 2+ on dipstick, then Urine Protein Creatinine (UPC) ratio should be calculated. If UPC ratio \>1, 24-hour urine protein should be obtained and the level should be \<1000 mg/24 hours for patient enrollment.Note: UPC ratio of spot urine is an estimation of the 24 hour urine protein excretion- a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using of the following formulae:\[urine protein\]/\[urine creatinine\] - if both protein and creatinine are reported in mg/dL \[(urine protein x 0.088\]/\[urine creatinine\] - if urine creatinine is reported in mmol/L
Medulloblastoma
Ependymoma
Anaplastic oligodendroglioma
1 to \<2 years, male max 0.6, female max 0.6
Platelet count ≥ 100,000/uL (transfusion independent)
Patient must have histological verification of one of the eligible diagnosis listed below. Biopsy is required at time of diagnosis, with the exception of optic pathway tumors. Patients with spinal cord disease are eligible if they have a lesion \>1 cm in 2 dimensions. The following histologies are eligible:
Hemoglobin ≥ 8.0 gm/dL (may receive pRBC transfusions)
Patient must have recovered from any surgical procedure before enrolling on this study.
Pleomorphic xanthoastrocytoma
Mixed glioma (including oligoastrocytoma)
Creatinine clearance or radioisotope GFR ≥70ml/min/1.73 m2 or
1 month to \< 6 months, male max 0.4, female max 0.4
16 years, male max 1.7, female max 1.4
Ganglioneuroma
Patient must have a life expectancy of \>8 weeks.
Infantile desmoplastic astrocytoma
Patient must have adequate liver function defined as:
Peripheral absolute neutrophil count (ANC) ≥1000/uL (must not have received G-CSF within the prior 7 days)
10 to \<13 years, male max 1.2, female max 1.2
Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy.
Astrocytoma variants: fibrillary, protoplasmic, mixed
Anaplastic astrocytoma
Other rare malignant CNS tumors (i.e., pineal blastoma, small cell astrocytoma, etc.)
6 months to \< 1 year, male max 0.5, female max 0.5
Patients receiving corticosteroids are eligible provided the dose is stable or decreasing for at least 7 days.
Patient must have adequate renal function defined as:
Oligodendroglial tumor
2 to \< 6 years, male max 0.8, female max 0.8
Anaplastic oligoastrocytoma
Glioblastoma multiforme (including giant cell and gliosarcoma types)
6 to \<10 years, male max 1.0, female max 1.0
Patient must have measurable residual disease, defined as tumor that is measurable in two perpendicular diameters on MRI. Diffuse leptomeningeal disease is not considered measurable.
Patient must have adequate bone marrow function (including status post-SCT) defined as:
Anaplastic ganglioglioma
13 to \<16 years, male max 1.5, female max 1.4
Pilocytic astrocytoma, including pilomyxoid variants
Patients with a seizure disorder are eligible if well-controlled on anticonvulsants. If on a non-enzyme inducing anticonvulsant, the irinotecan dose will be adjusted as outline in treatment plan.

Exclusion

Patient must not have serious and inadequately controlled cardiac arrhythmia
Patient must not have a known bleeding diathesis or coagulopathy.
Patient must not have a serious or non-healing wound, ulcer, or bone fracture.
Patient must not have a known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.
Patient must not require an intermediate surgical procedure ≤14 days prior to beginning therapy.
Patient must not have an uncontrolled infection.
Patient must not have received any growth factors ≤7 days of entry onto this study.
Patient must not have had myelosuppressive chemotherapy ≤ 3 weeks prior to entry onto this study (or 6 weeks if prior nitrosourea).
Patient must not be known to be HIV-positive on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with study therapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
Patient must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia, or antiphospholipid antibody syndrome). Testing is not required in patients without a thrombophilic history.
Patient must not require a major surgical procedure ≤ 21 days prior to beginning therapy.
Patient must not be receiving an investigational drug.
Patient must not have had significant vascular disease (e.g., Moya-Moya, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) ≤ 6 months prior to study entry.
Patient must not have a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure ≤ 6 months prior to study entry.
There should be no anticipation of need for major surgical procedures during the course of the study.
Patient must not require sedation for imaging purposes.
Patient must not be taking NSAIDS, clopidogrel, dipyridamole, or aspirin therapy \>81 mg/day.
Patient must not have received craniospinal radiotherapy or involved field radiotherapy to the local tumor (and/or tumor designated as "measurable" for protocol purposes) ≤ 24 weeks prior to study entry; focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry.
Patient must not have had any anti-neoplastic biologic agent ≤7 days prior to entry onto this study (or at least 3 half-lives for biologic agents with a long half-life).
Patient must not require a minor surgical procedure (i.e., Broviac line or infusaport placement) ≤ 7 days prior to beginning therapy, and the wound must be healed prior to initiation of therapy.
Patient must not have received bevacizumab, or other anti-VEGF inhibitor in the last 3 months.
Patient must not be pregnant or breastfeeding.
Patient must not have any contraindications to MRI imaging including implanted medical devices and metal objects which may be adversely affected by MRI imaging. All subjects will be required to complete a standard MRI screening form prior to imaging.
Patient must not be receiving any other anti-cancer agent.
Patient must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess ≤ 6 months prior to study entry.
Patient must not have evidence of a new CNS hemorrhage greater than 0.5cm on baseline MRI obtained ≤ 14 days prior to study enrollment.