Monoclonal Antibody Therapy and Docetaxel in Treating Women With Metastatic or Recurrent Breast Cancer

A Phase II Study Using SGN-15 (cBR96 - Doxorubicin Immunoconjugate) in Combination With Taxotere for the Treatment of Metastatic or Recurrent Breast Carcinoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining docetaxel and monoclonal antibody therapy in treating women who have metastatic or recurrent breast cancer.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: cBR96-doxorubicin immunoconjugate

Detailed Description

OBJECTIVES:

• Determine the toxicity and safety profile of doxorubicin-monoclonal antibody BR96 immunoconjugate (SGN-15) and docetaxel in women with metastatic or recurrent breast cancer.
• Determine the clinical response rate and duration of response of patients treated with this regimen.

OUTLINE: Patients receive doxorubicin-monoclonal antibody BR96 immunoconjugate (SGN-15) IV over 2 hours and docetaxel IV over 30 minutes on day 1 of weeks 1-6. Treatment repeats every 8 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study within 18-24 months.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center

Participation Criteria

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 confirmed metastatic or recurrent breast carcinoma

  • Unresectable disease
  • Previously treated with no more than 2 chemotherapy regimens for metastatic disease OR
  • Recurrent within 6 months of adjuvant chemotherapy

• Must have one of the following:

  • Measurable disease

  • Positive bone scan and elevation of serum tumor marker for adenocarcinoma

    • Serum levels must have increased over 2 consecutive measurements and exceed at least 2 times upper limit of normal
• Lewis-y antigen expression documented by immunohistochemistry
• No brain metastases that are uncontrolled or require active treatment (including steroids)

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Hemoglobin at least 10 g/dL
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No bleeding diathesis

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 2.5 times normal
• Alkaline phosphatase no greater than 2.5 times normal (unless documented bony metastasis present)
• Amylase/lipase less than 1.5 times normal
• Hepatitis B and C negative
• No hepatic failure

Renal:

• Creatinine no greater than 1.5 times upper limit of normal
• No renal failure

Cardiovascular:

• LVEF greater than 50% by echocardiogram or MUGA scan
• No congestive heart failure

Other:

• HIV negative
• No antibody present that detects monoclonal antibody BR96 in serum
• No peripheral neuropathy grade 2 or greater
• No dementia or altered mental status
• No other serious underlying medical condition that would preclude study participation
• No prior allergic reactions to recombinant human or murine proteins
• No uncontrolled peptic ulcer disease
• No active viral, bacterial, or systemic fungal infections
• No other primary malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No serious nonmalignant disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 8 weeks since prior therapeutic or diagnostic murine/humanized/human chimeric antibodies

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, carboplatin, mitomycin, or anthracyclines)
• No prior cumulative anthracycline of 300 mg/m2 or more
• No concurrent antineoplastic agents

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior hormonal therapy
• No concurrent hormonal therapy except estrogen replacement

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No other concurrent experimental agents
• No concurrent immunosuppressive medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Chair: Lisle M. Nabell, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Study Completion (Actual): April 1, 2003

Study Registration Dates

• First Submitted: January 4, 2002
• First Submitted That Met QC Criteria: June 26, 2003
• First Posted (Estimate): June 27, 2003

Study Record Updates

• Last Update Posted (Estimate): October 24, 2011
• Last Update Submitted That Met QC Criteria: October 21, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Doxorubicin; Immunoconjugates
• Other Study ID Numbers: CDR0000069079; SGEN-UAB-9912; UAB-9912