Celecoxib in Treating Women With Metastatic or Recurrent Breast Cancer

Evaluation Of Novel Therapeutic Agents (Celecoxib: NSC # 719627) Against Breast Cancer: An Innovative Randomized Phase II Trial Design

RATIONALE: Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor. It is not yet known which regimen of celecoxib is more effective in treating breast cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of two regimens of celecoxib in treating women who have metastatic or recurrent breast cancer

OBJECTIVES:

Primary

• Compare the progression-free survival of women with metastatic or recurrent breast cancer treated with 2 dose levels of celecoxib.

Secondary

• Compare the side effects of the 2 dose levels of this drug in these patients.
• Compare the overall survival of patients treated with the 2 dose levels of this drug.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to disease status at study entry (complete response vs partial response vs stable) and prior metastatic/recurrent chemotherapy regimens (1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral high-dose celecoxib twice daily.
• Arm II: Patients receive oral low-dose celecoxib twice daily. In both arms, treatment continues until first disease progression. At disease progression, treatment assignment is unblinded and treatment may continue at the treating physician's discretion. Patients initially randomized to the low-dose arm may either continue on that dosage or crossover to the high-dose arm. Patients initially randomized to the high-dose arm may continue on that dosage. Treatment after disease progression may continue for up to 12 months.

Patients are followed every 3 months for 1 year and then every 6 months for up to 4 years.

PROJECTED ACCRUAL: A total of 132 patients (88 in the high-dose arm and 44 in the low-dose arm) will be accrued for this study within 22 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer

  • Metastatic or recurrent disease documented by physical or radiographic examination
  • Isolated recurrence of breast cancer not considered eligible
  • Bone disease alone allowed

• At least 4 prior courses (or 4 months) of chemotherapy resulting in stable disease, partial response, or complete response

• Treated brain metastases allowed provided all of the following conditions are met:

  • Palliation achieved without evidence of progression for at least 3 months after completion of radiotherapy and/or surgical treatment
  • At least 30 days since prior dexamethasone or other corticosteroids
  • Documentation of another site of metastatic disease (in addition to brain metastases)

• Measurable or evaluable disease

• Pleural or peritoneal effusion as only manifestation of disease allowed if palliated by prior chemotherapy

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• CTC (ECOG) 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST or ALT no greater than 2.5 times ULN (5 times ULN if liver metastases present)
• Albumin at least 3.0 g/dL

Renal

• Creatinine no greater than 1.5 times ULN

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other active malignancy within the past 2 years except nonmelanoma skin cancer
• No active peptic ulcer disease
• No known hypersensitivity to sulfonamides, aspirin, or other NSAIDs, including celecoxib

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Concurrent trastuzumab (Herceptin) allowed if initiated at least 3 months prior to study entry

Chemotherapy

• See Disease Characteristics
• At least 6 weeks since prior chemotherapy
• No more than 2 prior chemotherapy regimens for recurrent or metastatic disease

Endocrine therapy

• See Disease Characteristics
• Prior hormonal therapy for metastatic disease allowed
• No concurrent hormonal therapy except hormones for noncancer-related conditions (e.g., insulin for diabetes)

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• Prior radiotherapy to the breast and for metastatic disease allowed
• No concurrent palliative radiotherapy

Surgery

• See Disease Characteristics

Other

• Prior adjuvant therapy for metastatic disease allowed
• Concurrent bisphosphonates allowed
• Concurrent low-dose aspirin (no greater than 325 mg/day) is allowed
• No other concurrent therapy with celecoxib or other nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib, aspirin, choline magnesium trisalicylate, ibuprofen, naproxen, etodolac, oxaprozin, diflunisal, nabumetone, or tolmetin)
• No concurrent fluconazole