Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00027729
• Other study ID #: 01-078
• Secondary ID: CDR0000069061MED
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 7, 2001
• Last updated: June 4, 2013
• Start date: June 2001
• Est. completion date: November 2004

Study information

• Verified date: June 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: November 2004
• Est. primary completion date: November 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• etaracizumab

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,