Cilengitide and Sunitinib Malate in Treating Patients With Advanced Solid Tumors or Glioblastoma Multiforme

This is an interventional treatment trial for Adult Giant Cell Glioblastoma Read More

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