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

• Sponsor: University of South Florida (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00090844
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 49
• Locations: 9
• Arms: 2
• Duration (Months): 46
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

• Study Type: Interventional
• 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: Jul 1, 2004
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Time to Resumption of Menses [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 44 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
2	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida	United States	33612-9497
3	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912-4000
4	MBCCOP - JHS Hospital of Cook County	Chicago	Illinois	United States	60612
5	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
6	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
7	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
8	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
9	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Published Results

Publications

None provided.

• Responsible Party: University of South Florida
• ClinicalTrials.gov Identifier: NCT00090844
• Other Study ID Numbers: CDR0000374991; P30CA076292; MCC-0203; NCI-7031
• First Posted: Sep 8, 2004
• Last Update Posted: Jan 28, 2021
• Last Verified: Jan 1, 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; Triptorelin Pamoate

Study Results

Participant Flow

Recruitment Details	49 female patients were enrolled between July 2003 and January 2007.

Arm/Group Title	Triptorelin	no Triptorelin
Arm/Group Description	Gonadotropin-releasing hormone [GnRH] analogue (triptorelin) during chemotherapy triptorelin : 3.75 mg TRELSTAR DEPOT (triptorelin) administered monthly as single intramuscular injection	No Gonadotropin-releasing hormone [GnRH] analogue (triptorelin) during chemotherapy
Period Title: Overall Study
STARTED	27	22
COMPLETED	26	21
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Triptorelin	no Triptorelin	Total
Arm/Group Description	GnRH analogue (triptorelin) during chemotherapy	no GnRH analogue (triptorelin) during chemotherapy	Total of all reporting groups
Overall Participants	27	22	49
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	27 100%	22 100%	49 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	39	38	39
Sex: Female, Male (Count of Participants)
Female	27 100%	22 100%	49 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 11.1%	2 9.1%	5 10.2%
Not Hispanic or Latino	24 88.9%	20 90.9%	44 89.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 9.1%	2 4.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 7.4%	1 4.5%	3 6.1%
White	25 92.6%	19 86.4%	44 89.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	27 100%	22 100%	49 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Triptorelin	no Triptorelin
Arm/Group Description	GnRH analogue (triptorelin) during chemotherapy triptorelin : 3.75 mg TRELSTAR DEPOT (triptorelin) administered monthly as single intramuscular injection	No GnRH analogue (triptorelin) during chemotherapy
Measure Participants	26	21
Median (Full Range) [months]	4.96	5.82

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Triptorelin	no Triptorelin
Arm/Group Description	GnRH analogue (triptorelin) during chemotherapy triptorelin: 3.75 mg TRELSTAR DEPOT (triptorelin) administered monthly as single intramuscular injection	No GnRH analogue (triptorelin) during chemotherapy
Measure Participants	26	21
Count of Participants [Participants]	3 11.1%	2 9.1%

Adverse Events

Arm/Group Title	Triptorelin		no Triptorelin
Arm/Group Description	GnRH analogue (triptorelin) during chemotherapy triptorelin : 3.75 mg TRELSTAR DEPOT (triptorelin) administered monthly as single intramuscular injection		No GnRH analogue (triptorelin) during chemotherapy
All Cause Mortality
	Triptorelin		no Triptorelin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Triptorelin		no Triptorelin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/27 (7.4%)		0/22 (0%)
Infections and infestations
Febrile Neutropenia	1/27 (3.7%)	1	0/22 (0%)	0
Vascular disorders
Thrombosis/thrombus/embolism	1/27 (3.7%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	Triptorelin		no Triptorelin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/27 (92.6%)		18/22 (81.8%)
Blood and lymphatic system disorders
Edema - limb	1/27 (3.7%)	1	2/22 (9.1%)	3
Endocrine disorders
hot flashes/flushes	23/27 (85.2%)	38	12/22 (54.5%)	18
Gastrointestinal disorders
Constipation	4/27 (14.8%)	5	2/22 (9.1%)	3
Distension/bloating, abdominal	3/27 (11.1%)	3	1/22 (4.5%)	1
Heartburn/dyspepsia	1/27 (3.7%)	2	3/22 (13.6%)	5
Mucositis/stomatitis (clinical exam)	2/27 (7.4%)	2	1/22 (4.5%)	1
Nausea	6/27 (22.2%)	8	7/22 (31.8%)	14
Vomiting	2/27 (7.4%)	2	2/22 (9.1%)	2
Mucositis/stomatitis (NOS)	0/27 (0%)	0	2/22 (9.1%)	2
General disorders
Fatigue	4/27 (14.8%)	5	1/22 (4.5%)	1
Insomnia	3/27 (11.1%)	3	2/22 (9.1%)	2
Sweating (diaphoresis)	4/27 (14.8%)	4	5/22 (22.7%)	6
Weight gain	3/27 (11.1%)	3	1/22 (4.5%)	1
Pain	10/27 (37%)	31	7/22 (31.8%)	16
Headaches	6/27 (22.2%)	13	5/22 (22.7%)	5
Pain - Other	2/27 (7.4%)	2	2/22 (9.1%)	2
Infections and infestations
Infection - Other	2/27 (7.4%)	2	2/22 (9.1%)	2
Infection with unknown ANC	4/27 (14.8%)	6	4/22 (18.2%)	5
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)	6/27 (22.2%)	7	5/22 (22.7%)	5
AST, SGOT (serum glutamic oxaloacetic transaminase)	3/27 (11.1%)	4	3/22 (13.6%)	3
Alkaline phosphatase	2/27 (7.4%)	4	0/22 (0%)	0
Glucose, serum-high (hyperglycemia)	9/27 (33.3%)	22	8/22 (36.4%)	14
Metabolic/Laboratory - Other	6/27 (22.2%)	10	0/22 (0%)	0
Potassium, serum-low (hypokalemia)	3/27 (11.1%)	3	1/22 (4.5%)	1
Nervous system disorders
Mood alteration	13/27 (48.1%)	15	6/22 (27.3%)	8
Neuropathy: sensory	2/27 (7.4%)	2	2/22 (9.1%)	2
Reproductive system and breast disorders
Vaginal dryness	3/27 (11.1%)	3	0/22 (0%)	0
Vaginal discharge (non-infectious)	2/27 (7.4%)	2	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/27 (7.4%)	2	0/22 (0%)	0
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other	3/27 (11.1%)	4	1/22 (4.5%)	1
Hair loss/alopecia (scalp or body)	11/27 (40.7%)	11	7/22 (31.8%)	7
Ulceration	0/27 (0%)	0	2/22 (9.1%)	2

Limitations/Caveats

Study closed to accrual early due to futility

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.