Leuprolide and Goserelin for Ovarian Function Suppression in Pre- or Peri-menopausal Women With Breast Cancer, OFS Trial
- Conditions
- Anatomic Stage I Breast Cancer AJCC v8Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Metastatic Breast Carcinoma
- Interventions
- Procedure: Biospecimen CollectionOther: Electronic Health Record ReviewOther: Questionnaire Administration
- Registration Number
- NCT07158021
- Lead Sponsor
- University of Michigan Rogel Cancer Center
- Brief Summary
This phase II trial compares leuprolide to goserelin for reducing estrogen production by the ovaries in pre- or peri-menopausal women with breast cancer. Estrogen can cause the growth of breast cancer cells. Both leuprolide and goserelin lower the amount of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. This study compares lower dose leuprolide, higher dose leuprolide, and goserelin for their ability to suppress the function of the ovaries to produce estrogen. Both doses of leuprolide may be as safe, tolerable and/or effective as goserelin in suppressing ovarian function in pre- or peri-menopausal women with breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 75
- Female subject aged ≥ 18 years
- Pre- or peri-menopausal patient, who had (1) menses within the 12 months prior to enrollment or (2) estradiol concentration above the postmenopausal range per institutional laboratory guidance within the 12 months prior to enrollment
- Planning to take GnRHa therapy in combination with oral endocrine therapy (tamoxifen, anastrozole, exemestane, or letrozole) for adjuvant treatment of stage 1-3 breast cancer or for treatment of metastatic breast cancer
- Not planning bilateral salpingo-oophorectomy during the 6-month study duration
- Completion of chemotherapy, if given. Concurrent use of trastuzumab, pertuzumab, bisphosphonate therapy, poly adenosine diphosphate-ribose polymerase (PARP) inhibitor therapy, cyclin D kinase 4/6 (CDK4/6) inhibitor, and/or phosphoinositide 3-kinase (PI3K) inhibitor therapy is permitted
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
- Prior bilateral salpingo-oophorectomy
- Pregnant or breast feeding, or plan to become pregnant during the study period
- Concomitant use of systemic or transdermal estrogen products
- Known allergy or hypersensitivity to goserelin or leuprolide, or any of the excipients in the medications
- Unable to take oral medications
- Any medical condition that would interfere with the absorption of endocrine therapy. Prior gastric bypass is permitted
- Patients with a prior or concurrent malignancy whose natural history or treatment, in the opinion of the treating investigator, has the potential to interfere with the safety or efficacy assessment of the investigational regimen
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (leuprolide) Biospecimen Collection Patients receive lower dose leuprolide IM on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm I (leuprolide) Electronic Health Record Review Patients receive lower dose leuprolide IM on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm I (leuprolide) Leuprolide Patients receive lower dose leuprolide IM on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm I (leuprolide) Questionnaire Administration Patients receive lower dose leuprolide IM on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm II (leuprolide) Biospecimen Collection Patients receive higher dose leuprolide IM on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm II (leuprolide) Electronic Health Record Review Patients receive higher dose leuprolide IM on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm II (leuprolide) Leuprolide Patients receive higher dose leuprolide IM on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm II (leuprolide) Questionnaire Administration Patients receive higher dose leuprolide IM on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm III (goserelin) Biospecimen Collection Patients receive goserelin SC on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm III (goserelin) Electronic Health Record Review Patients receive goserelin SC on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm III (goserelin) Goserelin Patients receive goserelin SC on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study. Arm III (goserelin) Questionnaire Administration Patients receive goserelin SC on day 1 of each cycle. Cycles repeat every 28 days for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study.
- Primary Outcome Measures
Name Time Method Proportion of participants with ultrasensitive estradiol concentration > 10 pg/ml During the first 24 weeks of therapy Analyses will primarily be descriptive reporting the overall and by treatment group proportions of women with ultrasensitive estradiol concentration and the corresponding exact binomial 95% confidence intervals over the first 24 weeks of gonadotropin releasing hormone agonist (GnRHa) therapy.
- Secondary Outcome Measures
Name Time Method Proportion of participants with ultrasensitive estradiol concentration > 10 pg/ml Any time after 4 weeks of initial GnRHa treatment administration, assessed cycle 3 day 1-cycle 7 day 1 (cycle length = 28 days) Will be described with corresponding 95% confidence intervals overall and by treatment group.
Change in Functional Assessment of Cancer Therapy-(FACT)-Endocrine Subscale (ES) Trial Outcome Index Up to 24 weeks Will use linear mixed-effects models with fixed effects for study group, time, and their interaction. For each outcome, a random intercept for each participant will be included to account for within-subject correlation. This approach allows for estimation of longitudinal trends in FACT-ES scores and assessment of whether changes over time differ between treatment arms. Missing data will be handled using maximum likelihood estimation under the assumption of missing at random (MAR).
Change in FACT-ES Endocrine Symptom Subscale Up to 24 weeks Will use linear mixed-effects models with fixed effects for study group, time, and their interaction. For each outcome, a random intercept for each participant will be included to account for within-subject correlation. This approach allows for estimation of longitudinal trends in FACT-ES scores and assessment of whether changes over time differ between treatment arms. Missing data will be handled using maximum likelihood estimation under the assumption of MAR.
Percentage of participants reporting discomfort of 6/10 or higher on the Discomfort of Injection questionnaire Before administration of the second GnRHa injection Will be described by study arm and with corresponding exact binomial 95% confidence intervals.
Receipt of GnRHa therapy within ± 1 day of planned dosing Up to 24 weeks Planned dosing should be given every 28 days. The proportion of patients who receive GnRHa therapy within ± 1 day of planned dosing will be reported overall and by study arm with corresponding exact binomial 95% confidence intervals.
Incidence of adverse events (AEs) Up to 24 weeks AEs will be graded and described using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be reported using descriptive statistics for each GnRHa study arm.
Trial Locations
- Locations (1)
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
University of Michigan Comprehensive Cancer Center🇺🇸Ann Arbor, Michigan, United StatesCancer AnswerLineContact800-865-1125CancerAnswerLine@med.umich.eduNorah L. HenryPrincipal Investigator