Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas

Completed · Phase 2

Conditions studied: Glioma

In brief

The purpose of this study is to determine the survival, disease response, and side effects of Tasigna® (nilotinib) in patients who have malignant gliomas and are positive for Platelet Derived Growth Factor Receptor (PDGFR) amplification. This study is designed to test the hypothesis that patients with malignant gliomas with PDGFR amplification are sensitive to PDGFR kinase inhibitors.

Key facts

Study ID

NCT01140568

Run by

David Piccioni, M.D., Ph.D

People needed

38

Starts

2010-04-21

Expected to finish

2019-01-01

Last updated by the study team

2020-05-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Ability to provide written informed consent prior to participation in the study and any related procedures being performed.
• Participants must have agreed to and signed an authorization for the release of their protected health information.
• Subjects must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary.
• Participants must have a life expectancy of at least 8 weeks.
• Patients greater than 18 years of age.
• Histologically documented diagnosis of proven glioblastoma (GBM), or anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and anaplastic mixed oligoastrocytoma (AMO). Patients are eligible if the original local pathology was lower-grade glioma. Pathology will be read centrally to confirm diagnosis.
• Documentation of amplified PDGFRA by fluorescent in-situ hybridization (FISH), colorimetric in-situ hybridization (CISH), or quantitative PCR from tumor tissue (=>3 copy number). Availability of unstained paraffin slides or the paraffin block of pretreatment baseline tissue is required for eligibility and for molecular analysis and would help to identify molecular predictors of outcome (all patients).
• Participants must have a Karnofsky Performance Status (KPS) ≥ 60.
• Adequate end organ function, defined as the following:
• Hematology:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• White blood cell (WBC) count ≥ 3.0 x 109/L
• Biochemistry:
• AST/SGOT and ALT/SGPT ≤ 2.5 x institution's ULN
• Total bilirubin ≤ 1.5 x institution's ULN
• Serum creatinine ≤ 1.5 x institution's ULN or 24-hour creatinine clearance ≥ 50 ml/min
• Alkaline phosphatase (ALP) ≤ 2.5 x ULN unless considered tumor related
• Patients must have the following laboratory values within normal limits (WNL) at the local institution lab or corrected to WNL with supplements prior to first dose of study medication.
• Potassium (WNL)
• Magnesium (WNL)
• Phosphorous (WNL)
• Calcium (WNL)
• Coagulation studies:

You may not qualify if…

• Patients who received PDGFR inhibitors (imatinib, sunitinib, nilotinib, etc.) previously are excluded (patients who received PDGFR antibody based treatment however are allowed).
• History of intratumoral or peritumoral hemorrhage if deemed significant by the treating physician.
• For patients requiring anticoagulation therapy, only therapeutic low molecular weight heparin or factor Xa inhibitors are permitted.
• Due to the potential interaction between nilotinib and enzyme-inducing anti-epileptic drugs (EIAED), only patients on non-enzyme inducing anti-epileptic drugs (NEIAED) or on no anti-epileptic drugs are eligible.
• Patient is < 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically neither significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• Female patients who are pregnant or breast-feeding, or intends to become pregnant during the study.
• Any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• Patient has a rare hereditary problem of galactose intolerance, severe lactase deficiency or of glucose-galactose malabsorption.
• Patients with any disease that will obscure toxicity or dangerously alter drug metabolism.
• Patient with electrolyte abnormality (e.g., hypokalemia, hypomagnesemia, hypophosphatemia, hyperkalemia, hypocalcemia, hyponatremia) unless the level can be corrected to normal levels prior to initiating study drug.
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea) prior to study entry, unless the disease is rapidly progressing.
• Concomitant use of any anti-cancer therapy or radiation therapy, or any other investigational agent.
• Impaired cardiac function including any of the following:
• Congenital long QT syndrome or a known family history of long QT syndrome;
• History or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (< 50 beats per minute)
• Inability to monitor the QT interval by ECG
• QTc > 450 msec on baseline ECG. If QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
• Myocardial infarction within 1 year of starting study drug
• Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
• Patients currently receiving treatment with strong CYP3A4 inhibitors and treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of CYP3A4 inhibitors (http://medicine.iupui.edu/clinpharm/ddis/table.asp)
• Patient currently receiving treatment with any medications that have the potential to prolong the QT interval and cannot be either discontinued or switched to a different medication prior to starting study drug. See link for a comprehensive list of agents that prolong the QT interval (http://www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm).
• Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery).
• Acute or chronic pancreatic disease.

Where it is running

• The Rebecca and John Moores UCSD Cancer Center — La Jolla, California, United States

Full record on ClinicalTrials.gov

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