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
- 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.
Masking: Open Label, Primary Purpose: Treatment
Mark D. Pegram, MD
Jonsson Comprehensive Cancer Center
United States: Federal Government
|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|