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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Breast Cancer

Thank you

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


- 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

- 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


- 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

- No more than 2 prior chemotherapy regimens, including adjuvant /neoadjuvant

- 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



- 18 and over


- Female

Menopausal status

- Not specified

Performance status

- WHO 0-2

Life expectancy

- At least 4 months


- Hemoglobin at least 10 g/dL

- Neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3


- 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)


- 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])


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


- 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


Biologic therapy

- See Disease Characteristics

- More than 2 weeks since prior growth factors to aid hematologic recovery

- No other concurrent immunotherapy


- 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


- More than 4 weeks since prior radiotherapy except for palliation

- No concurrent antitumor radiotherapy except for palliation


- More than 4 weeks since prior major surgery


- 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:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Mark D. Pegram, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center


United States: Federal Government

Study ID:




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



Jonsson Comprehensive Cancer Center, UCLA Los Angeles, California  90095-1781