Monoclonal Antibody HuHMFG1 in Treating Women With Locally Advanced or Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

An Open Label Phase I Study of Humanized Human Milk Fat Globule-1 (huHMFG1) Antibody in Patients With Locally Advanced or Metastatic Breast Cancer (TOPCAT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00096057
• Other study ID #: ROCHE-NP17787
• Secondary ID: UCLA-0402065-01C
• Status: Completed
• Phase: Phase 1
• First received: November 9, 2004
• Last updated: June 25, 2013
• Start date: May 2004
• Est. completion date: December 2007

Study information

• Verified date: April 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies such as HuHMFG1 can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of monoclonal antibody HuHMFG1 in treating women with locally advanced or metastatic breast cancer.

Description:

OBJECTIVES:

• Determine the safety and tolerability of monoclonal antibody HuHMFG1 in women with locally advanced or metastatic breast cancer.

• Determine a safe recommended dose and schedule of this drug in these patients.

• Determine the pharmacokinetic profile, in the absence of any other chemotherapy or endocrine agent, of this drug in these patients.

• Determine the antitumor activity of this drug in these patients.

• Determine time to progression in patients treated with this drug.

• Assess immunological markers (e.g., granzyme B, gamma interferon, and C1Q) for determining response to this drug in these patients.

• Assess markers of immunogenicity (e.g., human anti-human antibody) of this drug in these patients.

• Assess tumor markers (e.g., CA15.3 and CEA) in patients treated with this drug.

• Correlate, preliminarily, soluble HMFG1 antigen levels with pharmacokinetic data for this drug in these patients.

OUTLINE: This is an open-label, non-randomized, dose-escalation study.

Patients in cohorts 1 and 2 receive monoclonal antibody HuHMFG1 IV over 1-3 hours once every 21 days for doses 1 and 2. All subsequent dose intervals are based on individual half-life value of the drug, to be within 3 days of the estimated half-life in multiples of 7 days. Patients in cohorts 3 and 4 receive monoclonal antibody HuHMFG1 at the dosing interval determined in the first 2 cohorts. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of monoclonal antibody HuHMFG1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

All patients are followed at 4 weeks and then every 6 weeks for 6 months. Patients with an antitumor response or stable disease are followed every 12 weeks until disease progression or initiation of another antitumor treatment.

PROJECTED ACCRUAL: A total of 6-24 patients will be accrued for this study within 18 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer

• Locally advanced or metastatic disease

• No inflammatory breast cancer

• Measurable (RECIST) or evaluable disease (e.g., cytologically or radiologically detectable disease that does not fulfill RECIST criteria)

• Failed prior OR not a candidate for OR refused anthracycline- and taxane-containing chemotherapy

• Patients whose tumor overexpresses HER-2 must have failed prior trastuzumab (Herceptin®)

• No known CNS metastases

• No metastases accessible to complete surgical resection

• Unstained slides cut from formalin-fixed and paraffin-embedded tumor blocks available

• Appropriate tumor block also acceptable

• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• WHO 0-1

Life expectancy

• At least 4 months

Hematopoietic

• Hemoglobin = 10 g/dL

• Absolute neutrophil count = 1,500/mm^3

• WBC = 1,000/mm^3

• Platelet count = 100,000/mm^3

Hepatic

• Bilirubin = 1.5 mg/dL

• ALT or AST = 2.5 times upper limit of normal (ULN) (< 5 times ULN in patients with liver metastases) OR

• Alkaline phosphatase = 2.5 times ULN (< 5 times ULN in patients with liver metastases)

• Any degree of elevated alkaline phosphatase allowed provided it is due to bone metastases

Renal

• Creatinine = 1.5 times ULN OR

• Creatinine clearance > 60 mL/min

• Uric acid < 1.25 times ULN (for patients with hyperuricemia only)

• Calcium (corrected for serum albumin) < 11.5 mg/dL (for patients with hypercalcemia only)

Cardiovascular

• LVEF = 45% by MUGA or echocardiogram within the past 4 weeks

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or cervical intra-epithelial neoplasia

• No other uncontrolled illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• Prior biological therapy allowed

• More than 2 weeks since prior blood transfusions or growth factors to aid hematological recovery

• No other concurrent antitumor immunotherapy

Chemotherapy

• See Disease Characteristics

• More than 4 weeks since prior cytotoxic chemotherapy

• No more than 3 prior chemotherapy regimens, including adjuvant/neoadjuvant therapy

• No concurrent antitumor chemotherapy

Endocrine therapy

• Prior hormonal therapy allowed

• No concurrent corticosteroids except as physiologic replacement and/or for acute short-term treatment of, or prophylaxis against, infusion reactions

• No concurrent antitumor hormonal therapy

Radiotherapy

• See Disease Characteristics

• More than 4 weeks since prior radiotherapy (except for palliative radiotherapy)

• No concurrent antitumor radiotherapy, except for palliation to non-study lesions

• Irradiated area should be as small as possible and involve = 10% of the bone marrow in any given 4-week period

Surgery

• More than 4 weeks since prior major surgery

Other

• More than 30 days since prior investigational agents

• No other concurrent investigational agents

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• monoclonal antibody HuHMFG1

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,