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Pilot Biomarker Study of the Integrin AlphavBeta3 Antagonist Cilengitide (EMD121974) in Combination With Sunitinib

18 Years
Open (Enrolling)
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Pilot Biomarker Study of the Integrin AlphavBeta3 Antagonist Cilengitide (EMD121974) in Combination With Sunitinib


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


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

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.


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.

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

- 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

- 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.,

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Change in serum VEGFR2

Outcome Time Frame:

Over 14 days from the end of sunitinib to the end of course 1

Safety Issue:


Principal Investigator

Michael Maitland

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2009

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Brain Neoplasms
  • Glioblastoma
  • Gliosarcoma



University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470