Celecoxib and Trastuzumab in Treating Women With Metastatic Breast Cancer

Phase II Study of Celecoxib in HER-2/Neu Overexpressing Metastatic Breast Cancer Patients Who Have Failed Recombinant Humanized Anti-p 185HER Monoclonal Antibody Trastuzumab (HERCEPTIN)

RATIONALE: Celecoxib may be effective in preventing the further development of cancer. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining trastuzumab with celecoxib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining celecoxib and trastuzumab in treating women who have metastatic breast cancer that has not responded to previous trastuzumab.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: celecoxib; Biological: trastuzumab

Detailed Description

OBJECTIVES:

• Determine the efficacy of celecoxib and trastuzumab (Herceptin) in women with HER2/neu-overexpressing metastatic breast cancer that is refractory to prior trastuzumab.
• Determine the safety of celecoxib in these patients.

OUTLINE: At least 3 weeks after the last dose of prior chemotherapy, patients receive oral celecoxib twice daily. Patients continue or restart trastuzumab (Herceptin) IV over 30-90 minutes weekly or every 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within approximately 9 months.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering 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 proven metastatic breast cancer

  • HER2/neu-positive (overexpressing) tumor tissue
• Failed prior trastuzumab (Herceptin) therapy with or without chemotherapy
• Resected stage IV disease allowed if evidence of disease

• Bidimensionally measurable or evaluable disease

  • No lesions in previously irradiated field except nonbone lesions progressive after radiotherapy
  • No pleural effusions
  • No blastic or mixed bony metastases
  • No palpable abdominal masses
• No leptomeningeal disease

• Brain metastases allowed if:

  • No concurrent use of steroids
  • At least 3 months since prior brain irradiation
  • No evidence of progression of metastases

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Hemoglobin at least 8.0 g/dL
• Platelet count at least 100,000/mm^3

Hepatic:

• AST/ALT no greater than 2 times upper limit of normal (ULN)
• Bilirubin no greater than 1.5 times ULN

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• LVEF at least 50%

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No other prior malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer
• No other serious medical illness
• No severe infection
• No severe malnutrition
• No prior allergic reactions to sulfonamides or celecoxib

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• Prior trastuzumab (Herceptin) for breast cancer allowed, either as adjuvant/neoadjuvant or for metastatic disease

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior cytotoxic therapy for breast cancer allowed, either as adjuvant/neoadjuvant or for metastatic disease

Endocrine therapy:

• See Disease Characteristics
• At least 3 weeks since prior hormonal therapy
• Prior exogenous hormonal therapy for stage IV disease and/or as adjuvant therapy allowed

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• Prior localized radiotherapy allowed if no influence on the signal measurable lesion
• Concurrent localized radiotherapy allowed if no influence on the signal measurable lesion

Surgery:

• See Disease Characteristics
• At least 3 weeks since prior major surgery and recovered
• At least 2 weeks since prior minor surgery and recovered

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Chau T. Dang, MD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2000
• Study Completion (Actual): February 1, 2004

Study Registration Dates

• First Submitted: October 4, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 19, 2013
• Last Update Submitted That Met QC Criteria: December 18, 2013
• Last Verified: December 1, 2003

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; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cyclooxygenase 2 Inhibitors; Trastuzumab; Celecoxib
• Other Study ID Numbers: CDR0000068255; MSKCC-00078; NCI-G00-1869