Clinical trial NCT00068601: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Infertility
Menopausal Symptoms
Keywords: infertility
menopausal symptoms
stage II breast cancer
stage IIIA breast cancer
stage IA breast cancer
stage IB breast cancer
estrogen receptor-negative breast cancer
progesterone receptor-negative breast cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Cancer and Leukemia Group B
name: Eastern Cooperative Oncology Group
name: ETOP IBCSG Partners Foundation
First posted: 2003-09-11
Enrollment: 257
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Rate of Premature Ovarian Failure at 2 Years
timeFrame: 2 years
Secondary outcomes:
measure: Rate of Ovarian Dysfunction at 2 Years
timeFrame: 2 years
measure: Rate of Ovarian Dysfunction at 1 Year
timeFrame: 1 year
Other outcomes:
measure: Ovarian Reserve at 1 and 2 Years
timeFrame: 1 and 2 years
Locations:
city: North Sydney
country: Australia
facility: Mater Hospital - North Sydney
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Newcastle Mater Misericordiae Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital Cancer Centre
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Ballarat
country: Australia
facility: Ballarat Oncology and Haematology Services
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Center - Clayton Campus
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: East Ringwood
country: Australia
facility: Maroondah Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital - Melbourne
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Huy
country: Belgium
facility: Centre Hospitalier Hutois
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Liege
country: Belgium
facility: CHU Liege - Domaine Universitaire du Sart Tilman
city: Oostende
country: Belgium
facility: AZ Damiaan
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer-La Tourelle
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
city: Biella
country: Italy
facility: Ospedale degli Infermi - ASL 12
city: Carpi
country: Italy
facility: Ospedale Civile Ramazzini
city: Lecco
country: Italy
facility: Ospedale Alessandro Manzoni
city: Milano
country: Italy
facility: European Institute of Oncology
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Locarno
country: Switzerland
facility: Oncology Institute of Southern Switzerland - Locarno
city: Lugano
country: Switzerland
facility: Oncology Institute of Southern Switzerland - Lugano
city: Mendrisio
country: Switzerland
facility: Oncology Institute of Southern Switzerland - Mendrisio
city: Thun
country: Switzerland
facility: Regionalspital
Study officials:
affiliation: The Cleveland Clinic
name: Halle C Moore, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Loyola University
name: Kathy S. Albain, MD
role: STUDY_CHAIR
affiliation: Saint John's Cancer Institute
name: Silvana Martino, DO
role: STUDY_CHAIR
affiliation: Dana-Farber Cancer Institute
name: Ann H. Partridge, MD, MPH
role: STUDY_CHAIR
affiliation: Fox Chase Cancer Center
name: Lori J. Goldstein, MD
role: STUDY_CHAIR
affiliation: Peter MacCallum Cancer Centre, Australia
name: Kelly-Anne Phillips
role: STUDY_CHAIR
References:
citation: 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.