An Open Label Phase I/II Study of Humanized Human Milk Fat Globule-1 (THEREX) in Patients With Locally Advanced or Metastatic Breast Cancer Following Prior Anthracycline and Taxane Therapy
18 Years
N/A
Female
Breast Cancer
Trial Information
An Open Label Phase I/II Study of Humanized Human Milk Fat Globule-1 (THEREX) in Patients With Locally Advanced or Metastatic Breast Cancer Following Prior Anthracycline and Taxane Therapy
OBJECTIVES:
- Determine the safety and tolerability of monoclonal antibody HuHMFG1 in women with
locally advanced or metastatic breast cancer previously treated with anthracycline and
taxane-based therapy.
- Determine the maximum tolerated dose and appropriate schedule of this drug in these
patients.
- Determine the pharmacokinetic profile of this drug in these patients.
- Determine the tumor response rate, progression-free survival, and median survival of
patients treated with this drug.
- Analyze immunological markers for evaluation of disease status (e.g., in vitro analysis
of antibody-dependent cellular cytotoxicity, natural killer cell activity, complement
depletion, and tumor markers CA 15.3 and CEA) in patients treated with this drug.
OUTLINE: This is a dose-escalation, open-label, nonrandomized, multicenter study.
- Phase I: Patients receive monoclonal antibody HuHMFG1 IV over 1-3 hours once every 3
weeks for doses 1 and 2. All subsequent dose intervals are based on individual
half-life value of the drug. Patients receive at least 6 doses in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 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 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II:Patients receive monoclonal antibody HuHMFG1 as above at the MTD. Patients are
followed at 28 days.
PROJECTED ACCRUAL: Approximately 3-40 patients (3-15 patients for phase I and 19-25 patients
for phase II) will be accrued for this study within approximately 12 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed breast cancer
- Locally advanced or metastatic disease
- No inflammatory breast cancer
- Polymorphic epithelial mucin (PEM) antigen overexpression by immunohistochemistry
- Previously treated with an anthracycline and a taxane in any combination for breast
cancer
- No more than 2 prior chemotherapy regimens, including adjuvant /neoadjuvant
therapy
- No more than 1 prior regimen for distant metastatic disease
- Any number of prior hormonal or biologic therapy regimens allowed
- Measurable disease
- At least one unidimensionally measurable lesion not previously irradiated
- The following are not considered measurable lesions:
- Bone
- Leptomeningeal disease
- Ascites
- Pleural/pericardial effusion
- Lymphangitis cutis/pulmonis
- Abdominal masses not confirmed and followed by imaging techniques
- Cystic lesions
- No metastases accessible to complete surgical resection
- No CNS metastasis by CT scan
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Female
Menopausal status
- Not specified
Performance status
- WHO 0-2
Life expectancy
- At least 4 months
Hematopoietic
- Hemoglobin at least 10 g/dL
- Neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic
- Bilirubin no greater than 1.5 mg/dL
- ALT and AST no greater than 2.5 times upper limit of normal (ULN) (less than 5 times
ULN if liver metastases are present)
Renal
- Creatinine no greater than 1.5 times ULN OR
- Creatinine clearance greater than 60 mL/min
- No hyperuricemia (uric acid at least 1.25 times ULN)
- No hypercalcemia (calcium at least 11.5 mg/dL [corrected for serum albumin])
Cardiovascular
- LVEF at least 45% by MUGA or echocardiogram within the past 4 weeks
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3-6 months after
study participation
- No other prior malignancy within the past 5 years except adequately treated
nonmelanoma skin cancer or cervical intraepithelial neoplasia
- No other concurrent uncontrolled comorbid illness that represents unacceptable risk
in the opinion of the investigator
- No legal incapacity
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- More than 2 weeks since prior growth factors to aid hematologic recovery
- No other concurrent immunotherapy
Chemotherapy
- See Disease Characteristics
- More than 4 weeks since prior cytotoxic chemotherapy
- No concurrent chemotherapy for metastatic breast cancer
Endocrine therapy
- See Disease Characteristics
- No concurrent endocrine therapy for metastatic breast cancer
- No concurrent chronic corticosteroid therapy
- No concurrent high-dose corticosteroids
Radiotherapy
- More than 4 weeks since prior radiotherapy except for palliation
- No concurrent antitumor radiotherapy except for palliation
Surgery
- More than 4 weeks since prior major surgery
Other
- More than 2 weeks since prior blood transfusions to aid hematologic recovery
- No participation in any other investigational drug study
- No other concurrent investigational drugs
- No other concurrent antitumor therapy
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Mark D. Pegram, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000316264
NCT ID:
NCT00066547
Start Date:
May 2003
Completion Date:
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 |
|---|---|
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
