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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)

Phase 1
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

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)


- 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.

Inclusion Criteria


- 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

- Patients whose tumor overexpresses HER-2 must have failed prior trastuzumab

- 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



- 18 and over


- Female

Menopausal status

- Not specified

Performance status

- WHO 0-1

Life expectancy

- At least 4 months


- Hemoglobin ≥ 10 g/dL

- Absolute neutrophil count ≥ 1,500/mm^3

- WBC ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3


- 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

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


- 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


- LVEF ≥ 45% by MUGA or echocardiogram within the past 4 weeks


- 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


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


- 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


- 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


- More than 4 weeks since prior major surgery


- More than 30 days since prior investigational agents

- No other concurrent investigational agents

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Mark D. Pegram, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Jonsson Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

May 2004

Completion Date:

December 2007

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • Breast Neoplasms



M.D. Anderson Cancer Center at University of Texas Houston, Texas  77030
Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California  90095-1781
University of Colorado Cancer Center at UC Health Sciences Center Aurora, Colorado  80045