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

• ClinicalTrials.gov Identifier: NCT00068601
• Recruitment Status: Completed
• First Posted: September 11, 2003
• Results First Posted: April 4, 2017
• Last Update Posted: December 30, 2019
• Sponsor: SWOG Cancer Research Network
• Collaborators: National Cancer Institute (NCI); Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; ETOP IBCSG Partners Foundation
• Information provided by (Responsible Party): SWOG Cancer Research Network

Tracking Information

• First Submitted Date: September 10, 2003
• First Posted Date: September 11, 2003
• Results First Submitted Date: December 16, 2016
• Results First Posted Date: April 4, 2017
• Last Update Posted Date: December 30, 2019
• Study Start Date: October 2003
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 15, 2017)

Rate of Premature Ovarian Failure at 2 Years [ Time Frame: 2 years ]

Ovarian failure at two years is defined as amenorrhea (absence of menstrual bleeding) for the preceding six months AND the presence of follicle-stimulating hormone (FSH) in the post-menopausal range.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: February 15, 2017)

• Rate of Ovarian Dysfunction at 2 Years [ Time Frame: 2 years ]
  Ovarian dysfunction is defined as amenorrhea for the preceding three months and the presence of FSH, estradiol and/or inhibin B levels in the postmenopausal range.
• Rate of Ovarian Dysfunction at 1 Year [ Time Frame: 1 year ]
  Ovarian dysfunction is defined as amenorrhea for the preceding three months and the presence of FSH, estradiol and/or inhibin B levels in the postmenopausal range.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: February 15, 2017)

Ovarian Reserve at 1 and 2 Years [ Time Frame: 1 and 2 years ]

Measurements of ovarian reserve will consist of "Day 2 - 4" levels of FSH, estradiol and inhibin B during Month 12/13 and Month 24/25 (or if amenorrheic, anytime during Month 12/13 and Month 24/25).

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: S0230 Goserelin in Preventing Ovarian Failure in Women Receiving Chemotherapy for Breast Cancer
• Official Title: Phase III Trial of LHRH Analog Administration During Chemotherapy to Reduce Ovarian Failure Following Chemotherapy in Early Stage, Hormone-Receptor Negative Breast Cancer

Brief Summary

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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care

Condition

• Breast Cancer
• Infertility
• Menopausal Symptoms

Intervention

• Drug: cyclophosphamide
  Part of planned chemotherapy regimen
• Drug: goserelin acetate
  Given subcutaneously

Study Arms

• Active Comparator: Standard Chemotherapy
  Patients receive cyclophosphamide-containing chemotherapy alone.
  Intervention: Drug: cyclophosphamide
• Experimental: Chemotherapy Plus Goserelin
  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.
  Interventions:

  • Drug: cyclophosphamide
  • Drug: goserelin acetate

• Publications *: Moore HC, Unger JM, Phillips KA, Boyle F, Hitre E, Porter D, Francis PA, Goldstein LJ, Gomez HL, Vallejos CS, Partridge AH, Dakhil SR, Garcia AA, Gralow J, Lombard JM, Forbes JF, Martino S, Barlow WE, Fabian CJ, Minasian L, Meyskens FL Jr, Gelber RD, Hortobagyi GN, Albain KS; POEMS/S0230 Investigators. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 2015 Mar 5;372(10):923-32. doi: 10.1056/NEJMoa1413204.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 28, 2016): 257
• Original Enrollment: Not Provided
• Actual Study Completion Date: September 2016
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 49 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Hungary, Italy, New Zealand, Switzerland
• Removed Location Countries: Peru, Saudi Arabia, United States

Administrative Information

• NCT Number: NCT00068601
• Other Study ID Numbers: CDR0000327758; S0230 ( Other Identifier: SWOG ); CALGB-40401 ( Other Identifier: CALGB ); IBCSG-34-05 ( Other Identifier: IBCSG ); U10CA037429 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: SWOG Cancer Research Network
• Original Responsible Party: Not Provided
• Current Study Sponsor: SWOG Cancer Research Network
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• Cancer and Leukemia Group B
• Eastern Cooperative Oncology Group
• ETOP IBCSG Partners Foundation

Investigators

• Principal Investigator: Halle C Moore, MD; The Cleveland Clinic
• Study Chair: Kathy S. Albain, MD; Loyola University
• Study Chair: Silvana Martino, DO; Saint John's Cancer Institute
• Study Chair: Ann H. Partridge, MD, MPH; Dana-Farber Cancer Institute
• Study Chair: Lori J. Goldstein, MD; Fox Chase Cancer Center
• Study Chair: Kelly-Anne Phillips; Peter MacCallum Cancer Centre, Australia

• PRS Account: SWOG Cancer Research Network
• Verification Date: December 2019