Monoclonal Antibody HuHMFG1 in Treating Women With Locally Advanced or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00096057
First received: November 9, 2004
Last updated: June 25, 2013
Last verified: April 2007

November 9, 2004
June 25, 2013
May 2004
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Complete list of historical versions of study NCT00096057 on ClinicalTrials.gov Archive Site
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Monoclonal Antibody HuHMFG1 in Treating Women With Locally Advanced or Metastatic Breast Cancer
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)

RATIONALE: Monoclonal antibodies such as HuHMFG1 can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of monoclonal antibody HuHMFG1 in treating women with locally advanced or metastatic breast cancer.

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.

Interventional
Phase 1
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
Biological: monoclonal antibody HuHMFG1
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
December 2007
Not Provided

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00096057
ROCHE-NP17787, UCLA-0402065-01, CDR0000391212
Not Provided
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Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Mark D. Pegram, MD Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
April 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP