This trial is active, not recruiting.

Conditions adult anaplastic astrocytoma, adult diffuse astrocytoma, adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, adult mixed glioma, adult oligodendroglioma, adult pineal gland astrocytoma
Treatments sunitinib malate, pharmacological study
Phase phase 2
Targets VEGF, FLT-3, KIT, PDGF
Sponsor National Cancer Institute (NCI)
Start date June 2007
End date June 2009
Trial size 73 participants
Trial identifier NCT00499473, N01CM62203, N01CM62206, N01CM62207, NCI-2009-00215, OSU 06060


This phase II trial is studying how well sunitinib works in treating patients with recurrent malignant gliomas. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Non-EIAC patients receive oral sunitinib malate once daily for 4 consecutive weeks followed by 2 weeks of rest.
sunitinib malate SU11248
Given orally
pharmacological study pharmacological studies
Correlative studies
EIAC & OSU patients receive oral sunitinib malate as in stratum 1. Patients receive escalating doses of oral sunitinib malate until the maximum tolerated dose (MTD) is determined.
sunitinib malate SU11248
Given orally
pharmacological study pharmacological studies
Correlative studies

Primary Outcomes

Progression-free survival at 6 months (Stratum 1)
time frame: From time to registration to up to 6 months
Maximum tolerable dose based on dose-limiting toxicity of sunitinib in patients receiving EIAC (Stratum 2)
time frame: From the time of first treatment with sunitinib until completion of treatment, assessed up to 30 days
Dose resulting in steady-state trough
time frame: At baseline (day 8) and days 15, 22, and 23

Secondary Outcomes

Confirmed objective response (complete response[CR] or partial response [PR])
time frame: On 2 successive evaluations at least 4 weeks apart
Percentage of patients progression free
time frame: At 12 months after the start of treatment
Progression-free survival (Stratum 2)
time frame: Time from study registration to date of disease progression or last follow up
Overall survival
time frame: Time from study registration to date of death from any cause or last follow-up

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Stratum 1: - Currently not receiving an enzyme-inducing anticonvulsant - Patients receiving non-enzyme inducing anticonvulsants are eligible for this stratum - Histologically confirmed WHO grade IV astrocytoma (glioblastoma multiforme [GBM]) including gliosarcoma - Stratum 2 (USA patients only): - Currently on stable dose of an enzyme-inducing anticonvulsant (with confirmed therapeutic serum levels) for at least 2 weeks prior to study registration including any of the following: - Phenytoin - Carbamazepine - Phenobarbital - Histologically confirmed grade IV astrocytoma (GBM), gliosarcoma, grade III astrocytoma, oligodendroglioma, or mixed oligoastrocytoma - All patients must have unequivocal evidence of tumor progression by MRI or CT scan performed no longer than 14 days prior to study registration - Patients undergoing surgery for progressive disease with nonmeasurable disease on post-operative MRI, ideally obtained within 48 hours of surgery, (i.e., macroscopic gross total resection) are eligible - ECOG performance status 0-2 (Karnofsky ≥ 60%) - Life expectancy > 3 months - Leukocytes ≥ 3,000/μL - Absolute neutrophil count ≥ 1,500/μL - Platelet count ≥ 100,000/μL - Hemoglobin ≥ 9 g/dL - Serum calcium ≤ 12.0 mg/dL - Total bilirubin within normal institutional limits (ULN) - AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN - Creatinine < 1.5 X institutional ULN - Patients must have QTc < 500 msec - The following groups of patients are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO or MUGA: - Those with a history of class II heart failure who are asymptomatic on treatment - Those with prior anthracycline exposure - Those who have received central thoracic radiation that included the heart in the radiotherapy port - Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation - All women of childbearing potential must have a negative pregnancy test prior to receiving sunitinib malate - Patients with a history of QTc prolongation (defined as a QTc interval >= 500 msec), serious ventricular arrhythmia (VT or VF > 3 beats in a row) or other significant ECG abnormalities are excluded - Patients with poorly controlled hypertension (systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg) are ineligible - Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib malate tablets are excluded - Patients with any of the following conditions are excluded: - Serious or non-healing wound, ulcer, or bone fracture - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment - History of myocardial infarction, cardiac arrhythmia, stable or unstable angina, symptomatic congestive heart failure, or coronary or peripheral artery bypass graft or stenting within 12 months prior to study entry - Class III or IV heart failure as defined by the NYHA functional classification system - Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible - Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections requiring antibiotics or psychiatric illness/social situations that would limit compliance with study requirements are ineligible - Pregnant women are excluded from this study - Breastfeeding should be discontinued if the mother is treated with sunitinib malate - Patients are eligible if they received up to 1 previous chemotherapy regimen - ≥ 12 weeks must have elapsed from the completion of radiation therapy - ≥ 4 weeks from previous non-nitrosoureas-based cytotoxic chemotherapy - ≥ 6 weeks from any nitrosoureas - ≥ 2 weeks from last cytostatic chemotherapy such as erlotinib hydrochloride or tamoxifen - Patients who have undergone previous stereotactic radiosurgery, intratumoral chemotherapy, or brachytherapy are eligible if functional imaging (PET or SPECT scan, MR spectroscopy, or dynamic MRI) supports the diagnosis of recurrent tumor or recurrent disease is confirmed histologically - Concurrent steroids allowed provided the patients is on a stable or decreasing dose for at least 7 days prior to baseline tumor assessment (MRI and/or CT scan) - Patients who have received prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, or VEGF Trap) are ineligible - Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin or enoxaparin are excluded, although warfarin doses of up to 2 mg daily are permitted for prophylaxis of thrombosis - Low molecular weight heparin is permitted provided the patient's PT INR is < 1.5 - Use of agents with proarrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, or flecainide) is not permitted during the study - No other investigational or commercial agents or non-investigational therapy designed to treat the brain malignancy (i.e., radiation therapy, systemic or intratumoral chemotherapy, biological agents, immunotherapy, or hormonal therapy) is allowed during the study period - HIV-positive patients on combination antiretroviral therapy are ineligible Exclusion Criteria: - History of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate - Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or radiation therapy within 12 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier - At least 4 weeks must have elapsed since any major surgery

Additional Information

Official title A Pharmacokinetic and Phase 2 Study of Sunitinib Malate in Recurrent Malignant Gliomas
Principal investigator Robert Cavaliere
Description PRIMARY OBJECTIVES: I. To assess the efficacy of sunitinib malate in patients with recurrent malignant gliomas as measured by 6-month progression-free survival. II. To determine the lower of the dose of sunitinib malate in patients receiving enzyme-inducing anti-convulsants that would achieve similar serum drug and metabolite concentrations as that in patients not receiving enzyme-inducing anticonvulsants or the maximum tolerated dose in the same population. SECONDARY OBJECTIVES: I. To examine the toxicity and safety of sunitinib malate in patients with the above noted tumors. II. To evaluate tumor responses in the stated patients. III. To evaluate progression-free and overall survival in the stated patients. OUTLINE: This is a multicenter study. Patients are stratified according to use of enzyme-inducing anticonvulsants (EIAC) (yes vs no). STRATUM 1 (non-EIAC): Patients receive oral sunitinib malate once daily for 4 consecutive weeks followed by 2 weeks of rest. STRATUM 2 (EIAC & OSU patients only): Patients receive oral sunitinib malate as in stratum 1. Patients receive escalating doses of oral sunitinib malate until the maximum tolerated dose (MTD) is determined. Patients undergo blood sample collection periodically for pharmacokinetic studies. Samples are analyzed for plasma concentrations of sunitinib malate via LC/MS/MS method. In both strata, treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Trial information was received from ClinicalTrials.gov and was last updated in March 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).