Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer

Study Overview
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Brief Summary
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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/II trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced colorectal cancer that has not responded to irinotecan.

Detailed Description
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OBJECTIVES: Determine the recommended phase II dose of monoclonal antibody anti-anb3 integrin in patients with irinotecan-refractory advanced colorectal cancer. Determine the safety and tolerance of this drug in these patients. Determine any antitumor activity of this drug in these patients. Determine the objective response rate, response duration, and time to progression in patients treated with this drug. Determine the pharmacokinetics of this drug in these patients. OUTLINE: This is a dose-escalation study. Patients receive monoclonal antibody anti-anb3 integrin IV over 30 minutes once weekly on weeks 1-52 in the absence of disease progression or unacceptable toxicity. Patients with responding disease may continue therapy. Cohort of 4-6 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 4 or 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at that dose in the phase II portion of the study. Patients are followed every 3 months for 2 years. PROJECTED ACCRUAL: A total of 4-24 patients will be accrued for phase I of this study and a total of 40 patients will be accrued for phase II of this study.

Official Title
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Phase I/II Study of MEDI-522, A Humanized Monoclonal Antibody Directed Against the Human Alpha V Beta 3 Integrin, in Patients With Irinotecan-Refractory Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: etaracizumab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed advanced colorectal cancer Disease progression while receiving an irinotecan-containing regimen for metastatic colorectal cancer OR Disease recurrence within 6 months after completing an irinotecan-containing regimen in the adjuvant setting At least 1 measurable lesion (for phase II only) At least 20 mm by x-ray, CT scan, MRI, or photograph Recurrent disease after surgery or radiotherapy is considered measurable if it has been at least 4 weeks since treatment and measurable disease is outside the port of prior radiotherapy or there is evidence of disease progression within the port of prior radiotherapy The following are not considered measurable: Pleural effusion Ascites Osteoblastic lesion or evidence of disease on bone scan alone Progressive irradiated lesions alone Bone marrow involvement Brain metastases Malignant hepatomegaly by physical exam alone Chemical markers (e.g., carcinoembryonic antigen) No known brain metastases or primary brain tumors No symptomatic pleural effusion or ascites requiring paracentesis No clinical evidence of bowel obstruction PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin greater than 10.0 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dL AST/ALT no greater than 5 times upper limit of normal (ULN) PT/PTT less than ULN OR INR less than 1.12 No hepatitis virus infection Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 50 mL/min Cardiovascular: No prior myocardial infarction No angina No uncontrolled hypertension (systolic blood pressure greater than 150 mm Hg) No prior cerebrovascular accident or transient ischemic attack Pulmonary: No respiratory insufficiency requiring oxygen treatment No lymphangitic involvement of lungs Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for 30 days before, during, and for 30 days after study Thyroxine and thyroid-stimulating hormone normal No hematemesis, melena, hematochezia, or gross hematuria No prior significant adverse reaction to a humanized monoclonal antibody No known HIV infection No active infection requiring systemic anti-infective therapy No other medical or psychological condition or behavior, including substance dependence or abuse, that would preclude study No other malignancy within the past 5 years except basal cell skin cancer or completely excised carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: Prior immunotherapy with approved agents allowed No prior monoclonal antibody anti-anb3 integrin or its precursor (MEDI-523) No other concurrent immunotherapy Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy No concurrent palliative chemotherapy Endocrine therapy: No concurrent hormonal therapy Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy Surgery: See Disease Characteristics At least 4 weeks since prior surgery and surgical wounds must have healed Other: Recovered from all prior therapy At least 4 weeks since prior investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: etaracizumab|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent colon cancer, recurrent rectal cancer