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

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00096057

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: monoclonal antibody HuHMFG1	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Study Start Date :

May 1, 2004

Actual Study Completion Date :

Dec 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
2	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado	United States	80045
3	M.D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009