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

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Drug Toxicity; Hormone Changes
• Intervention / Treatment: Drug: triptorelin

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 Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 44 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Trelstar Depot
NO_INTERVENTION: no triptorelin; No GnRH analogue (triptorelin) during chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Resumption of Menses	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	Baseline, end of chemotherapy then 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemotherapy-related Amenorrhea	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.	Baseline, end of chemotherapy then 5 years

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Pamela N. Munster, MD, H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

Helpful Links

• Published Results

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (ACTUAL): May 1, 2008
• Study Completion (ACTUAL): May 1, 2008

Study Registration Dates

• First Submitted: September 7, 2004
• First Submitted That Met QC Criteria: September 7, 2004
• First Posted (ESTIMATE): September 8, 2004

Study Record Updates

• Last Update Posted (ACTUAL): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage I breast cancer; drug/agent toxicity by tissue/organ; hormone changes
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Triptorelin Pamoate
• Other Study ID Numbers: CDR0000374991; P30CA076292 (U.S. NIH Grant/Contract); MCC-0203 (OTHER: Moffitt CCOP Research Base); NCI-7031 (OTHER: National Cancer Institute Division of Cancer Prevention)