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


N/A
18 Years
N/A
Open (Enrolling)
Both
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


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.


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

Type of Study:

Interventional

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:

No

Principal Investigator

Michael Maitland

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-01455

NCT ID:

NCT01122888

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

Name

Location

University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470