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)
18 Years
N/A
Female
Breast Cancer
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)
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Mark D. Pegram, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
ROCHE-NP17787
NCT ID:
NCT00096057
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
Name | Location |
|---|---|
| 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 |
