Clinical Trial Finder

Inclusion Criteria:

• - Histologically confirmed solid tumor or malignant glioblastoma multiforme meeting >= 1 of the following criteria: - Disease refractory to standard therapy.

• - No standard therapy exists.

• - Sunitinib malate monotherapy would be appropriate management.

• - Measurable disease is not required.

• - Previously treated brain metastases or primary brain neoplasms allowed provided patient is not receiving concurrent corticosteroids.

• - Karnofsky performance status 70-100% - Absolute neutrophil count (ANC) >= 1,500/μL.

• - White blood cell count (WBC) >= 3,000/μL.

• - Platelet count >= 100,000/μL.

• - Hemoglobin >= 9 g/dL.

• - Total bilirubin normal (unless due to documented Gilbert syndrome) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal (ULN) (< 5 times ULN in the presence of liver metastases) - Creatinine normal OR creatinine clearance >= 60 mL/min.

• - Serum calcium =< 12.0 mg/dL.

• - QTc < 500 msec.

• - Patients with any of the following are allowed provided they have New York Heart Association (NYHA) class I-II cardiac function and undergo a baseline echocardiogram (ECHO)/multiple gated acquisition (MUGA): - History of class II heart failure and asymptomatic on treatment.

• - Prior anthracycline exposure.

• - Previously treated with central thoracic radiotherapy that included the heart in the radiotherapy port.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective barrier contraception.

• - No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate.

• - No concurrent uncontrolled illness including, but not limited to, any of the following: - Ongoing or active infection.

• - Symptomatic congestive heart failure.

• - Unstable angina pectoris.

• - Cardiac arrhythmia.

• - Psychiatric illness and/or social situation that would limit compliance with study requirements.

• - No pre-existing thyroid abnormality for which thyroid function cannot be maintained in the normal range with medication.

• - No documented thrombosis (pulmonary embolism or deep vein thrombosis) within the past 6 months.

• - No known coagulopathy or thrombophilia.

• - No proven gastric or duodenal ulcer or clinically significant gastrointestinal (GI) blood loss within the past 6 weeks.

• - No history of central nervous system (CNS) hemorrhage.

• - No life-threatening bleeding diathesis within the past 6 months.

• - No history of serious ventricular arrhythmia (i.e., ventricular fibrillation or ventricular tachycardia >= 3 beats in a row) or other significant electrocardiogram (ECG) abnormalities.

• - No poorly controlled hypertension (i.e., systolic blood pressure (BP) >= 150 mm Hg or diastolic BP >= 100 mm Hg) - No condition that would impair the ability to swallow and retain sunitinib malate tablets, including any of the following: - GI tract disease resulting in an inability to take oral medications or a requirement for IV alimentation.

• - Prior surgical procedures affecting absorption.

• - Active peptic ulcer disease.

• - No gastrostomy, jejunostomy, or other forms of enteral tube feeding modalities.

• - None of the following conditions: - Serious or non-healing wound or ulcer.

• - Abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days.

• - Cerebrovascular accident or transient ischemic attack within the past 12 months.

• - Myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months.

• - NYHA class III or IV heart failure.

• - Radiographically or physiologically diagnosed usual interstitial pneumonitis (UIP) or non-specific interstitial pneumonitis (NSIP) - No bone fracture within the past 12 months.

• - No other concurrent anticancer agents or therapies.

• - More than 4 weeks since prior radiotherapy or systemic antineoplastic therapy (6 weeks for nitrosoureas, mitomycin C, or bevacizumab) and recovered.

• - More than 2 weeks since prior hormone replacement therapy or hormonal contraceptives.

• - More than 1 month since prior surgery.

• - At least 7 days since prior and no concurrent CYP3A4 inhibitors.

• - At least 12 days since prior and no concurrent CYP3A4 inducers.

• - Prior luteinizing hormone-releasing hormone agonists for hormone-refractory prostate cancer allowed.

• - Prior antiangiogenic agents (e.g., sorafenib, pazopanib, AZD2171 [cediranib maleate], PTK787 [vatalanib], or VEGF Trap [ziv-aflibercept]) allowed provided there is no disease progression.

• - No prior cilengitide or sunitinib malate.

• - No prior bevacizumab.

• - No other concurrent investigational agents.

• - No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients.

• - No concurrent agents with proarrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, or flecainide) - No concurrent palliative radiotherapy.

• - No other concurrent chemotherapy or biologic agents.

• - No concurrent medications that may cause QTc prolongation.

• - No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin) - Up to 2 mg of daily warfarin for the prophylaxis of thrombosis allowed.

• - Low-molecular weight heparin allowed provided prothrombin time (PT)/international normalized ratio (INR) =< 1.5.

- No concurrent grapefruit juice

PRIMARY OBJECTIVES:

• I. Determine the effect of cilengitide on changes in serum VEGFR2, a pharmacodynamic biomarker of sunitinib malate effects on endothelial function, during the withdrawal phase of a course of sunitinib malate in patients with advanced solid tumors or glioblastoma multiforme.

SECONDARY OBJECTIVES:

• I. Determine the effect of cilengitide exposure on changes in VEGFR2 over the 14-day interval from the end of sunitinib malate administration to the end of course 1 in these patients.

• II. Test the safety and efficacy of this regimen in these patients.

• III. Develop serum collagen c-telopeptide crosslinks (CTx) as a pharmacodynamic marker for cilengitide.

OUTLINE: COURSE I: Patients receive oral sunitinib malate on days 1-14 (weeks 1-2). Patients are then randomized to 1 of 2 treatment arms. ARM I: Patients receive cilengitide IV over 1 hour twice in weeks 3 and 4. ARM II: Patients do not receive treatment in weeks 3 and 4. COURSE II: Patients in both arms then receive oral sunitinib malate on days 1-14 and cilengitide IV over 1 hour twice in weeks 3 and 4. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up periodically.

Arms

Experimental: Arm I (course 1)

Patients receive cilengitide IV over 1 hour twice weekly for 2 weeks.

Other: Arm II (course 1)

Patients do not receive treatment and undergo a 2-week rest period.

Interventions

Drug: - Cilengitide

Given IV

Other: - Clinical Observation

Patients undergo a 2-week rest period

Other: - Laboratory Biomarker Analysis

Correlative studies