Title
Monoclonal Antibody Therapy in Treating Patients With Advanced Solid Tumors
Phase I Study of Monoclonal Antibody Anti-Anb3 Integrin in Patients With Advanced Solid Tumors
Phase
Phase 1Lead Sponsor
Wayne State UniversityStudy Type
InterventionalStatus
WithdrawnIndication/Condition
Unspecified Adult Solid Tumor, Protocol SpecificIntervention/Treatment
anti-anb3 integrin octreotide vatalanib ...Study Participants
0RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.
PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced solid tumors.
OBJECTIVES:
Determine the maximum tolerated dose and recommended phase II dose of monoclonal antibody anti-anb3 integrin in patients with advanced solid tumors.
Determine the toxic effects of this drug in these patients.
Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
Determine the potential anti-tumor activity of this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive monoclonal antibody anti-anb3 integrin IV over 30 minutes weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of monoclonal antibody anti-anb3 integrin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated as above at that dose level.
PROJECTED ACCRUAL: A total of 27-33 patients will be accrued for this study within 9-11 months.
Inclusion Criteria DISEASE CHARACTERISTICS: Histologically or cytologically confirmed solid tumor that is unresponsive to currently available therapies or for which no known effective treatment exists Measurable or evaluable disease Must have clinical or radiological evidence of disease Disease must be accessible to biopsy and imaging studies No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 Life expectancy At least 3 months Hematopoietic Absolute neutrophil count at least 2,000/mm^3 Platelet count at least 100,000/mm^3 No prior bleeding disorder Hepatic Bilirubin no greater than 1.2 mg/dL alanine aminotransferase test (ALT) and Aspartate Aminotransferase (AST) no greater than 2.5 times upper limit of normal (ULN) Prothrombin time (PT)/ partial thromboplastin time (PTT) no greater than ULN Renal Creatinine less than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study Willing to be premedicated for delayed contrast-enhanced MRI No prior claustrophobia No dementia or altered mental status that would preclude informed consent No other uncontrolled concurrent illness No ongoing or active infection No psychiatric illness or social situations that would preclude study compliance No immunodeficiency HIV negative Must be willing to receive blood products No thyroid disease Thyroxine and thyroid-stimulating hormone no greater than ULN PRIOR CONCURRENT THERAPY: Biologic therapy At least 4 weeks since prior immunotherapy Exclusion Criteria Chemotherapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Prior taxanes allowed No concurrent chemotherapy Endocrine therapy No concurrent hormonal therapy except: Concurrent hormonal replacement therapy Concurrent medication for maintaining castrate status in patients with progressive hormone refractory prostate cancer Radiotherapy At least 4 weeks since prior radiotherapy and recovered No prior radiotherapy to more than 25% of the bone marrow No concurrent radiotherapy Surgery More than 4 weeks since prior surgery Other No other concurrent investigational or commercial agents or therapies for the malignancy No other concurrent antitumor therapy
