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

June 25, 2013 updated by: Jonsson Comprehensive Cancer Center

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center at UCLA
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center at UC Health Sciences Center
    • Texas
      • Houston, Texas, United States, 77030-4009
        • M.D. Anderson Cancer Center at University of Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: NONE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jonsson Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Study Completion (ACTUAL)

December 1, 2007

Study Registration Dates

First Submitted

November 9, 2004

First Submitted That Met QC Criteria

November 8, 2004

First Posted (ESTIMATE)

November 9, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

June 26, 2013

Last Update Submitted That Met QC Criteria

June 25, 2013

Last Verified

April 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ROCHE-NP17787
  • UCLA-0402065-01
  • CDR0000391212 (REGISTRY: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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