Impact of Formulation Change on Ovarian Suppression in Young Breast Cancer Patients. (IFOCOS)

May 20, 2026 updated by: Jian Zhang,MD, Fudan University

A Multicenter, Prospective, Randomized Controlled Study-Impact of Formulation Change on Ovarian Suppression in Young Breast Cancer Patients (IFOCOS)

This is a multicenter, prospective, randomized controlled, phase II study. The primary objective is to evaluate the effect of endocrine therapy modification (switching from a 3-month to a 1-month GnRHa) versus continuation of the 3-month GnRHa on E2 control at 3 months in young patients with hormone receptor-positive breast cancer and iOFS.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

In China, breast cancer occurs at a young age, with a peak incidence at 40-49 years; patients aged ≤45 years account for 20%-24% of cases, and this proportion is increasing. Ovarian function suppression (OFS) combined with aromatase inhibitor (AI) or tamoxifen (TAM), with or without CDK4/6 inhibitors, has become a preferred adjuvant endocrine therapy for intermediate to high-risk premenopausal hormone receptor-positive (HR+) patients with HR+ breast cancer. AI is effective in premenopausal women only when ovarian estrogen production is suppressed, which can be achieved with GnRH agonists (GnRHa). The 3-month GnRHa formulation is commonly preferred in the real world due to its convenience and reduced injection frequency; however, its effectiveness compared with the 1-month formulation remains a concern.

Among premenopausal patients receiving GnRHa combined with AI or TAM, approximately 8% experience incomplete ovarian function suppression (iOFS, E2 ≥30 pg/mL). Persistent iOFS may reduce the efficacy of endocrine therapy and potentially increase the risk of disease recurrence. Current clinical guidelines recommend monitoring serum estradiol (E2) levels during GnRHa treatment and suggest potential management strategies, including switching GnRHa formulations from 3-month to 1-month or modifying endocrine therapy (e.g., AI to TAM). However, evidence supporting these strategies is largely derived from retrospective studies or small case series, and prospective data remain limited. This multicenter, prospective, randomized, phase II study is designed to evaluate whether switching from a 3-month to a 1-month GnRHa can reduce E2 levels to <30 pg/mL within 3 months in premenopausal HR+ young breast cancer patients with iOFS. This study will also assess the long-term efficacy and safety of this strategy.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Step 1：iOFS detection phase

  1. Female, aged ≥18 and ≤45 years;
  2. Histologically confirmed hormone receptor-positive (HR+) (estrogen receptor [ER] and/or progesterone receptor [PR] ≥1%) and human epidermal growth factor receptor 2-negative (HER2-) early invasive breast cancer (stage I-III according to the American Joint Committee on Cancer [AJCC], version 8)；
  3. Completed curative surgery, with prior (neo)adjuvant chemotherapy and radiotherapy completed if applicable;
  4. Currently receiving adjuvant therapy with a 3-month GnRH agonist (GnRHa) plus aromatase inhibitor (AI) or tamoxifen (TAM), with or without CDK4/6 inhibitors (excluding abemaciclib due to its potential interference with estradiol monitoring), for ≥1 dose, and presenting with estradiol (E2) ≥30 pg/mL within 28 days prior to enrollment (measured by CLIA).
  5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; adequate bone marrow, hepatic, renal, and cardiac function.
  6. Voluntarily sign a written informed consent form before the trial screening.

Step 2：Randomized treatment phase

  1. iOFS confirmed using the SEMS assay (E2 ≥30 pg/mL);
  2. Ongoing adjuvant therapy with a 3-month GnRHa plus AI or TAM, with or without CDK4/6 inhibitors.
  3. No evidence of disease progression.

Exclusion Criteria:

Step 1：iOFS detection phase

  1. Bilateral breast cancer, inflammatory breast cancer, or distant metastasis;
  2. Use of GnRHa for ovarian function preservation;
  3. History of ovarian resection or ablation; planned pregnancy or breastfeeding;
  4. Concomitant use of hormonal agents other than estrogen, progesterone, selective estrogen receptor modulators (SERM), or selective estrogen receptor degraders (SERD);
  5. Severe uncontrolled comorbidities;
  6. Other malignancies within the past 5 years (except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma);
  7. Failure to comply with follow-up or psychiatric disorders.

Step 2：Randomized treatment phase

a)Prior conversion from a 3-month GnRHa to a 1-month GnRHa.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: 1-month GnRH + endocrine therapy
1-month GnRH (goserelin 3.6 mg depot or goserelin 3.6 mg implant or leuprolide 3.75 mg depot) +endocrine therapy (aromatase inhibitor/tamoxifen±CDK4/6 inhibition)
Drug: 1-month GnRH
1-month GnRH (goserelin 3.6 mg depot or goserelin 3.6 mg implant or leuprolide 3.75 mg depot) +endocrine therapy (aromatase inhibitor/tamoxifen±CDK4/6 inhibition)
Active Comparator: Active Comparator: Control
3-month GnRH (goserelin 10.8 mg implant or leuprolide 11.25 mg depot) + endocrine therapy (aromatase inhibitor/tamoxifen±CDK4/6 inhibition)
Drug: 3-month GnRH
3-month GnRH (goserelin 10.8 mg implant or leuprolide 11.25 mg depot) + endocrine therapy (aromatase inhibitor/tamoxifen±CDK4/6 inhibition)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants with E2 <30 pg/mL at 3 Months
Time Frame: 3 months post randomization
The primary endpoint is defined as the proportion of patients with E2 <30 pg/mL at 3 months, comparing patients who switch to GnRHa 1M versus those who continue GnRHa 3M therapy.
3 months post randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with E2 <30 pg/mL at 6 months after randomization
Time Frame: 6 months post randomization
This endpoint is defined as the proportion of patients with E2 <30 pg/mL at 6 months, comparing patients who switch to GnRHa 1M versus those who continue GnRHa 3M therapy.
6 months post randomization
Time to adequate ovarian function suppression
Time Frame: Assessed over a period of up to 12 months following randomization
This endpoint is defined as the time from the first occurrence of iOFS to the first measurement of E2 <30 pg/mL.
Assessed over a period of up to 12 months following randomization
Patient Age
Time Frame: At randomization
Age of participants at the time of randomization, categorized by iOFS status (Persistent vs. Transient).
At randomization
3-year invasive disease-free survival in patients who switch to GnRHa 1M versus those who continue GnRHa 3M therapy
Time Frame: From the date of randomization until the date of locoregional recurrence, distant metastasis, second primary breast cancer, or death from any cause, up to 3 months
Invasive disease-free survival is defined as the time from randomization to the first occurrence of locoregional recurrence, distant metastasis, second primary breast cancer, or death from any cause.
From the date of randomization until the date of locoregional recurrence, distant metastasis, second primary breast cancer, or death from any cause, up to 3 months
3-year invasive disease-free survival in patients with persistent iOFS and those with transient iOFS
Time Frame: From the date of randomization until the date of locoregional recurrence, distant metastasis, second primary breast cancer, or death from any cause, up to 3 months
From the date of randomization until the date of locoregional recurrence, distant metastasis, second primary breast cancer, or death from any cause, up to 3 months
Intraclass Correlation Coefficient (ICC) for the Consistency of the SEMS Method
Time Frame: post SEMS assay
The consistency of the SEMS method will be assessed by calculating the Intraclass Correlation Coefficient (ICC) between GnRHa 1M and GnRHa 1M at the post-assay time point.
post SEMS assay
Adverse events
Time Frame: From the date of treatment initiation until the date of disease progression, intolerable toxicities, death, withdrawal of consent, or completion of planned 3-year postoperative follow-up, whichever occurred first
Adverse events will be graded according to the NCI-CTCAE Version 5.0.
From the date of treatment initiation until the date of disease progression, intolerable toxicities, death, withdrawal of consent, or completion of planned 3-year postoperative follow-up, whichever occurred first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

May 14, 2026

First Submitted That Met QC Criteria

May 20, 2026

First Posted (Actual)

May 28, 2026

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IFOCOS

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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