S0230 Goserelin in Preventing Ovarian Failure in Women Receiving Chemotherapy for Breast Cancer

SWOG Cancer Research Network

Status and phase: Completed; Phase 3

Conditions: Breast Cancer; Infertility; Menopausal Symptoms

Treatments: Drug: goserelin acetate; Drug: cyclophosphamide

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00068601

CALGB-40401 (Other Identifier)

IBCSG-34-05 (Other Identifier)

CDR0000327758

U10CA037429 (U.S. NIH Grant/Contract)

S0230 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Goserelin blocks hormone production in the ovaries. It is not yet known whether ovarian suppression using goserelin will prevent ovarian failure (early menopause) in women receiving chemotherapy for breast cancer.

PURPOSE: This randomized phase III trial is studying how well giving goserelin together with chemotherapy works compared with chemotherapy alone in preventing early menopause in women with stage I, stage II, or stage IIIA breast cancer.

Full description

OBJECTIVES:

Primary

• Compare the rate of premature ovarian failure in women with stage I-IIIA hormone receptor-negative breast cancer treated with chemotherapy with vs without goserelin.

Secondary

• Compare the rate of ovarian dysfunction in patients treated with these regimens.
• Compare ovarian reserve in patients treated with these regimens.
• Describe the pregnancy rates in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to age (under 40 vs 40 to 49) and planned chemotherapy regimen (3- to 4-month/course anthracycline-based vs 6- to 8-month/course anthracycline-based vs 3- to 4-month/course non-anthracycline-based vs 6- to 8-month/course non-anthracycline-based). Patients are randomized to 1 of 2 treatment arms.

• Arm 1: Patients receive cyclophosphamide-containing chemotherapy alone. Patients are followed at 1, 2, and 5 years.
• Arm 2: Patients receive goserelin subcutaneously once every 4 weeks beginning 1 week before start of cyclophosphamide-containing chemotherapy. Treatment continues until completion of chemotherapy in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 416 patients (208 per treatment arm) will be accrued for this study within 3 years.

Enrollment: 257 patients

Sex: Female

Ages: 18 to 49 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer

  • Stage I-IIIA
  • Operable disease

• Bilateral synchronous invasive breast cancer allowed provided primary tumors were diagnosed no more than 1 month apart and both tumors are hormone receptor negative

• Must be planning to receive 3-8 months of a preoperative or postoperative chemotherapy regimen containing alkylating agents (anthracyclines or non-anthracyclines), meeting 1 of the following criteria:

  • 3-month/4-course anthracycline-based regimen
  • 6- to 8-month/course anthracycline-based regimen
  • 6- to 8-month/course non-anthracycline-based regimen

• Hormone receptor status:

  • Estrogen receptor negative
  • Progesterone receptor negative

PATIENT CHARACTERISTICS:

Age

• 18 to 49

Sex

• Female

Menopausal status

• Premenopausal

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Fertile patients must use effective barrier contraception
• No other prior malignancy except adequately treated basal cell or squamous cell skin cancer or any in situ cancer from which the patient has been disease-free for at least 5 years after treatment with curative intent

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior cytotoxic chemotherapy

Endocrine therapy

• No other concurrent hormonal therapy

Radiotherapy

• Concurrent radiotherapy to the breast, chest wall, or lymph nodes allowed

Surgery

• See Disease Characteristics

Other

• Concurrent participation in other therapeutic clinical trials, including SWOG-S0221, allowed

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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257 participants in 2 patient groups

Standard Chemotherapy

Active Comparator group

Description:

Patients receive cyclophosphamide-containing chemotherapy alone.

Treatment:

Drug: cyclophosphamide

Chemotherapy Plus Goserelin

Experimental group

Description:

Patients receive goserelin subcutaneously once every 4 weeks beginning 1 week before start of cyclophosphamide-containing chemotherapy. Treatment continues until completion of chemotherapy in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: cyclophosphamide

Drug: goserelin acetate