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

Phase III Trial of LHRH Analog Administration During Chemotherapy to Reduce Ovarian Failure Following Chemotherapy in Early Stage, Hormone-Receptor Negative Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Infertility; Menopausal Symptoms
• Intervention / Treatment: Drug: cyclophosphamide; Drug: goserelin acetate

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
• Enrollment (Actual): 257
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Mater Hospital - North Sydney
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Waratah, New South Wales, Australia, 2298
      • Newcastle Mater Misericordiae Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital Cancer Centre
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Ballarat Oncology And Haematology Services
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Center - Clayton Campus
    • East Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Centre
    • East Ringwood, Victoria, Australia, 3135
      • Maroondah Hospital
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital - Melbourne
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Belgium
  • Huy, Belgium, 4500
    • Centre Hospitalier Hutois
  • Leuven, Belgium, B-3000
    • U.Z. Gasthuisberg
  • Liege, Belgium, B-4000
    • CHU Liege - Domaine Universitaire du Sart Tilman
  • Liege, Belgium, 4000
    • Centre Hospitalier Régional de la Citadelle
  • Oostende, Belgium, 8400
    • AZ Damiaan
  • Verviers, Belgium, B-4800
    • Centre Hospitalier Peltzer-La Tourelle
• Hungary
  • Budapest, Hungary, 1122
    • National Institute of Oncology
• Italy
  • Bergamo, Italy, 24100
    • Ospedali Riuniti di Bergamo
  • Biella, Italy, 13900
    • Ospedale degli Infermi - ASL 12
  • Carpi, Italy, 41012
    • Ospedale Civile Ramazzini
  • Lecco, Italy, 23900
    • Ospedale Alessandro Manzoni
  • Milano, Italy, 20141
    • European Institute of Oncology
• New Zealand
  • Auckland, New Zealand, 1
    • Auckland City Hospital
• Switzerland
  • Bellinzona, Switzerland, CH-6500
    • Oncology Institute of Southern Switzerland
  • Bern, Switzerland, CH-3010
    • Inselspital Bern
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
  • Locarno, Switzerland, CH-6601
    • Oncology Institute of Southern Switzerland - Locarno
  • Lugano, Switzerland, CH-6900
    • Oncology Institute of Southern Switzerland - Lugano
  • Mendrisio, Switzerland, CH-6850
    • Oncology Institute of Southern Switzerland - Mendrisio
  • Thun, Switzerland, 3600
    • Regionalspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Chemotherapy; Patients receive cyclophosphamide-containing chemotherapy alone.	Drug: cyclophosphamide; Part of planned chemotherapy regimen
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.	Drug: cyclophosphamide; Part of planned chemotherapy regimen; Drug: goserelin acetate; Given subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Premature Ovarian Failure at 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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Ovarian Dysfunction at 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.	2 years
Rate of Ovarian Dysfunction at 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.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ovarian Reserve at 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).	1 and 2 years

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI); Eastern Cooperative Oncology Group; Cancer and Leukemia Group B; ETOP IBCSG Partners Foundation
• Investigators: Study Chair: Silvana Martino, DO, Saint John's Cancer Institute; Principal Investigator: Halle C Moore, MD, The Cleveland Clinic; 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

Publications and helpful links

General 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.

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: September 10, 2003
• First Submitted That Met QC Criteria: September 10, 2003
• First Posted (Estimate): September 11, 2003

Study Record Updates

• Last Update Posted (Actual): December 30, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; infertility; stage II breast cancer; stage IA breast cancer; stage IB breast cancer; estrogen receptor-negative breast cancer; progesterone receptor-negative breast cancer; menopausal symptoms
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Infertility; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Goserelin
• Other Study ID Numbers: CDR0000327758; U10CA037429 (U.S. NIH Grant/Contract); S0230 (Other Identifier: SWOG); CALGB-40401 (Other Identifier: CALGB); IBCSG-34-05 (Other Identifier: IBCSG)