Pilot Biomarker Study of the Integrin AlphavBeta3 Antagonist Cilengitide (EMD121974) in Combination With Sunitinib
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Change in serum VEGFR2
Study Overview
Brief Summary
This clinical trial is studying how well giving cilengitide together with sunitinib malate works in treating patients with advanced solid tumors or glioblastoma multiforme. Cilengitide and sunitinib malate may stop the growth of tumor cells by blocking blood flow to the tumor. Giving cilengitide together with sunitinib malate may kill more tumor cells. Studying samples of blood in the laboratory from patients receiving cilengitide and sunitinib malate may help doctors understand the effect of these drugs on biomarkers.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
- +21 more not shown
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (course 1)
Patients receive cilengitide IV over 1 hour twice weekly for 2 weeks.
Intervention: Cilengitide (Drug)
Arm I (course 1)
Patients receive cilengitide IV over 1 hour twice weekly for 2 weeks.
Intervention: Laboratory Biomarker Analysis (Other)
Arm II (course 1)
Patients do not receive treatment and undergo a 2-week rest period.
Intervention: Clinical Observation (Other)
Arm II (course 1)
Patients do not receive treatment and undergo a 2-week rest period.
Intervention: Laboratory Biomarker Analysis (Other)
Outcomes
Primary Outcomes
Change in serum VEGFR2
Time Frame: Over 14 days from the end of sunitinib to the end of course 1
Secondary Outcomes
- Progression-free survival(Assessed up to 30 days after completion of study treatment)
- Serum type I collagen c-telopeptide crosslink measurements(Up to 30 days after completion of study treatment)
- Comparison of the change in serum VEGFR2 in courses 1 and 2(Over 14 days)
- Toxicity rates, graded using the NCI CTCAE version 4.0(Up to 30 days after completion of study treatment)
- Response rate evaluated using RECIST criteria(Up to 30 days after completion of study treatment)