Triptorelin for Preserving Ovarian Function in Premenopausal Women Receiving Chemotherapy for Early-Stage Breast Cancer

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as triptorelin, may protect normal ovarian cells from the side effects of chemotherapy.

PURPOSE: This randomized phase II trial is studying how well triptorelin works in preserving ovarian function in premenopausal women who are receiving chemotherapy for early-stage breast cancer.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Hormone Changes; Drug Toxicity	Drug: triptorelin	Phase 2

Detailed Description:

OBJECTIVES:

Primary

• Determine the protective effect of chemical ovarian suppression using triptorelin on the preservation of ovarian function in premenopausal women with early-stage operable breast cancer undergoing adjuvant or neoadjuvant systemic chemotherapy.

Secondary

• Determine the rate of chemotherapy-related amenorrhea in patients treated with this drug.
• Determine the value of inhibin A and B as alternative markers of premature ovarian failure in patients treated with this drug.
• Determine quality of life of patients treated with this drug.
• Determine disease-free and overall survival of patients treated with this drug.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (< 35 years vs 35 to 39 years vs > 39 years); concurrent neoadjuvant or adjuvant systemic chemotherapy (fluorouracil, epirubicin, and cyclophosphamide [6 courses] OR fluorouracil, doxorubicin, and cyclophosphamide [6 courses] vs doxorubicin and cyclophosphamide [AC] [4 courses] vs doxorubicin and cyclophosphamide [AC] [4 courses] followed by a taxane [4 courses]); and hormone receptor status (estrogen receptor [ER]- AND progesterone receptor [PR]-negative vs ER- OR PR-positive).

• Arm I: Beginning within 1-4 weeks before the start of chemotherapy, patients receive triptorelin intramuscularly once monthly for 4-6 months during neoadjuvant or adjuvant systemic chemotherapy.
• Arm II: Patients receive neoadjuvant or adjuvant systemic chemotherapy only. Quality of life is assessed at baseline, monthly during treatment, every 6 months for 2 years, and then annually for 3 years.

Patients are followed every 6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 138 patients (69 per treatment arm) will be accrued for this study within 35 months.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	49 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Supportive Care
Official Title:	Preservation of Ovarian Function in Young Women Treated With (Neo) Adjuvant Chemotherapy for Breast Cancer: A Randomized Trial Using the Gonadotropin-releasing Hormone (GnRH) Agonist (Triptorelin) During Chemotherapy
Study Start Date :	July 2004
Actual Primary Completion Date :	May 2008
Actual Study Completion Date :	May 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: triptorelin; GnRH analogue (triptorelin) during chemotherapy	Drug: triptorelin; 3.75 mg TRELSTAR DEPOT (triptorelin) administered monthly as single intramuscular injection; Other Name: Trelstar Depot
No Intervention: no triptorelin; No GnRH analogue (triptorelin) during chemotherapy

Outcome Measures

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Primary Outcome Measures :

1. Time to Resumption of Menses [ Time Frame: Baseline, end of chemotherapy then 5 years ]
   Ovarian function as assessed by follicle stimulating hormone (FSH) and record of menses every 6 months beginning in month 6 for 2 years and then annually for 3 years

Secondary Outcome Measures :

1. Chemotherapy-related Amenorrhea [ Time Frame: Baseline, end of chemotherapy then 5 years ]
   Chemotherapy-related amenorrhea as assessed by record of menses monthly during treatment. Record of menses is completed by patient throughout their time on study through chemotherapy and for 5 years.
2. Alternative Markers of Ovarian Failure as Assessed by Inhibin A and Inhibin B Every 6 Months Beginning in Month 6 for 2 Years and Then Annually for 3 Years [ Time Frame: Baseline, end of chemotherapy then 5 years ]
   Inhibin A & inhibin B are collected at baseline, end of chemotherapy, then every 6 months for 2 years then annually for 3 more years. Inhibin A & Inhibin B are markers of ovarian failure.
3. Quality of Life as Assessed by FACT-ES Monthly During Treatment, Every Very 6 Months Beginning in Month 6 for 2 Years and Then Annually for 3 Years [ Time Frame: Baseline, through chemotherapy then 5 years ]
   FACT-ES (v4/4a) quality of life validated tool combines 18 item endocrine subscale (ES) with standardized breast cancer quality of life measure. Administered monthly during treatment, every very 6 months beginning in month 6 for 2 years and then annually for 3 years.
4. Disease-free Survival Every Very 6 Months Beginning in Month 6 for 2 Years and Then Annually for 3 Years [ Time Frame: 5 years after end of chemotherapy ]
   Every 6 months for 2 years then annual for 3 more years. Patients will be seen, laboratory specimens will be drawn. Menses records will be collected and reviewed. Concomitant medications will be updated.

Eligibility Criteria

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Ages Eligible for Study:	up to 44 Years (Child, Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

  • Early-stage, operable disease
• Scheduled to receive adjuvant or neoadjuvant systemic chemotherapy for breast cancer

• Hormone receptor status:

  • Meets 1 of the following criteria:

    • Estrogen receptor (ER)- OR progesterone receptor (PR)-positive
    • ER- AND PR-negative
• No history of premature ovarian failure

PATIENT CHARACTERISTICS:

Age

• Under 45

Sex

• Female

Menopausal status

• Premenopausal

  • Follicle-stimulating hormone levels < 40 IU/L at baseline AND at least 2 menstrual periods within the past 6 months
• No first-degree relative menopausal at < 40 years of age

Performance status

• Eastern Cooperative Oncology Group [ECOG] 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Fertile patients must use effective non-hormonal methods of contraception
• No prior osteoporosis or other non-malignant systemic disease that would preclude prolonged follow-up
• No known allergies to gonadotrophin-releasing hormone agonists
• No other cancer except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior chemotherapy

Endocrine therapy

• At least 2 weeks since prior oral contraceptives

• No prior fertility treatment

  • Clomiphene or pergonal for polycystic ovarian disease allowed

• No other concurrent oral or transdermal hormonal therapy, including any of the following:

  • Estrogen
  • Progesterone
  • Androgens
  • Aromatase inhibitors
  • Hormone replacement therapy
  • Oral contraceptives

Radiotherapy

• No prior ovarian radiotherapy

Surgery

• No prior bilateral oophorectomy
• No plans for oophorectomy or hysterectomy within the next 2 years

Other

• At least 1 week since prior warfarin

Exclusion Criteria:

• History of premature ovarian failure
• Over 45 years of age
• First-degree relative menopausal at < 40 years of age
• Pregnant or nursing
• Prior osteoporosis or other non-malignant systemic disease that would preclude prolonged follow-up
• Known allergies to gonadotrophin-releasing hormone agonists
• Other cancer besides nonmelanoma skin cancer
• Prior chemotherapy
• Prior ovarian radiotherapy
• Prior bilateral oophorectomy

Contacts and Locations

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Locations

United States, California
CCOP - Bay Area Tumor Institute
Oakland, California, United States, 94609-3305
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Georgia
MBCCOP - Medical College of Georgia Cancer Center
Augusta, Georgia, United States, 30912-4000
United States, Illinois
MBCCOP - JHS Hospital of Cook County
Chicago, Illinois, United States, 60612
United States, Missouri
CCOP - Cancer Research for the Ozarks
Springfield, Missouri, United States, 65807
Hulston Cancer Center at Cox Medical Center South
Springfield, Missouri, United States, 65807
United States, North Dakota
CCOP - MeritCare Hospital
Fargo, North Dakota, United States, 58122
United States, Texas
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Washington
CCOP - Northwest
Tacoma, Washington, United States, 98405-0986

Sponsors and Collaborators

University of South Florida

National Cancer Institute (NCI)

Investigators

Study Chair:	Pamela N. Munster, MD	H. Lee Moffitt Cancer Center and Research Institute

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	University of South Florida
ClinicalTrials.gov Identifier:	NCT00090844 History of Changes
Other Study ID Numbers:	CDR0000374991; P30CA076292 ( U.S. NIH Grant/Contract ); MCC-0203 ( Other Identifier: Moffitt CCOP Research Base ); NCI-7031 ( Other Identifier: National Cancer Institute Division of Cancer Prevention )
First Posted:	September 8, 2004
Results First Posted:	January 21, 2013
Last Update Posted:	January 31, 2013
Last Verified:	January 2013

Keywords provided by University of South Florida:

drug/agent toxicity by tissue/organ; hormone changes; stage I breast cancer; stage II breast cancer

Additional relevant MeSH terms:

Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Chemically-Induced Disorders; Triptorelin Pamoate	Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents