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

RATIONALE: 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.

Study Overview

• Status: Withdrawn
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Procedure: anti-cytokine therapy; Procedure: antiangiogenesis therapy; Procedure: growth factor antagonist therapy; Procedure: antibody therapy; Procedure: monoclonal antibody therapy; Procedure: biological response modifier therapy; Drug: monoclonal antibody anti-anb3 integrin

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Patricia LoRusso, DO, Harper Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2002

Study Registration Dates

• First Submitted: January 24, 2003
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 16, 2014
• Last Update Submitted That Met QC Criteria: January 15, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Mitosis Modulators; Antibodies; Immunoglobulins; Immunologic Factors; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Mitogens; Antibodies, Anti-Idiotypic
• Other Study ID Numbers: CDR0000258300; WSU-C-2453; NCI-5496