Leuprolide and Goserelin for Ovarian Function Suppression in Pre- or Peri-menopausal Women With Breast Cancer, OFS Trial

Phase 2RecruitingNCT07158021

University of Michigan Rogel Cancer Center75 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Anatomic Stage I Breast Cancer AJCC v8 Anatomic Stage II Breast Cancer AJCC v8 Anatomic Stage III Breast Cancer AJCC v8

Interventions

Biospecimen CollectionPROCEDURE

Undergo blood sample collection

Electronic Health Record ReviewOTHER

Ancillary studies

GoserelinDRUG

Given SC

LeuprolideDRUG

Given IM

Questionnaire AdministrationOTHER

Ancillary studies

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * Prior bilateral salpingo-oophorectomy * Known to be pregnant or breastfeeding (negative pregnancy test will be confirmed prior to study treatment initiation) * 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

Outcomes

Primary Outcomes

Proportion of participants with ultrasensitive estradiol concentration > 10 pg/ml

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.

Time frame: During the first 24 weeks of therapy

Secondary Outcomes

Proportion of participants with ultrasensitive estradiol concentration > 10 pg/ml

Will be described with corresponding 95% confidence intervals overall and by treatment group.

Time frame: At 4 weeks after initial GnRHa treatment administration

Proportion of participants with ultrasensitive estradiol concentration > 10 pg/ml

Will be described with corresponding 95% confidence intervals overall and by treatment group.

Time frame: Any time after 4 weeks of initial GnRHa treatment administration, assessed cycle 3 day 1-cycle 7 day 1 (cycle length = 28 days)

Change in Functional Assessment of Cancer Therapy-(FACT)-Endocrine Subscale (ES) Trial Outcome Index

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).

Time frame: Up to 24 weeks

Change in FACT-ES Endocrine Symptom Subscale

Time frame: Up to 24 weeks

Percentage of participants reporting discomfort of 6/10 or higher on the Discomfort of Injection questionnaire

Will be described by study arm and with corresponding exact binomial 95% confidence intervals.

Time frame: At the day following initial GnRHa injection

Percentage of participants reporting discomfort of 6/10 or higher on the Discomfort of Injection questionnaire

Will be described by study arm and with corresponding exact binomial 95% confidence intervals.

Time frame: Before administration of the second GnRHa injection

Receipt of GnRHa therapy within ± 1 day of planned dosing

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.

Time frame: Up to 24 weeks

Incidence of adverse events (AEs)

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.

Time frame: Up to 24 weeks

Leuprolide and Goserelin for Ovarian Function Suppression in Pre- or Peri-menopausal Women With Breast Cancer, OFS Trial

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts