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

Phase 2
Terminated
Conditions
Breast Cancer
Hormone Changes
Drug Toxicity
Interventions
Registration Number
NCT00090844
Lead Sponsor
University of South Florida
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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
Female
Target Recruitment
49
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
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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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
triptorelintriptorelinGnRH analogue (triptorelin) during chemotherapy
Primary Outcome Measures
NameTimeMethod
Time to Resumption of MensesBaseline, 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
NameTimeMethod
Chemotherapy-related AmenorrheaBaseline, 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.

Trial Locations

Locations (9)

MBCCOP - JHS Hospital of Cook County

🇺🇸

Chicago, Illinois, United States

MBCCOP - Medical College of Georgia Cancer Center

🇺🇸

Augusta, Georgia, United States

CCOP - Cancer Research for the Ozarks

🇺🇸

Springfield, Missouri, United States

CCOP - Bay Area Tumor Institute

🇺🇸

Oakland, California, United States

CCOP - MeritCare Hospital

🇺🇸

Fargo, North Dakota, United States

Hulston Cancer Center at Cox Medical Center South

🇺🇸

Springfield, Missouri, United States

CCOP - Scott and White Hospital

🇺🇸

Temple, Texas, United States

CCOP - Northwest

🇺🇸

Tacoma, Washington, United States

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

🇺🇸

Tampa, Florida, United States

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