NCT07671885

Brief Summary

Young HOPE/JCOG2402 is a multicenter, randomized phase III study designed to evaluate response-guided therapy following neoadjuvant endocrine therapy to optimize adjuvant treatment in premenopausal HR+/HER2- Breast Cancer. Premenopausal women with intermediate-risk HR-positive/HER2-negative breast cancer derive benefit from the addition of chemotherapy to endocrine therapy. However, previous studies have demonstrated that patients who achieve an endocrine response (Ki-67 ≤10%) following neoadjuvant endocrine therapy have excellent outcomes without chemotherapy, irrespective of menopausal status. These findings suggest that endocrine therapy response may serve as a predictive biomarker to identify premenopausal patients who can safely omit chemotherapy. The primary objective of this study is to evaluate the non-inferiority of an ET response-guided treatment strategy compared with standard surgery followed by adjuvant therapy. The study aims to increase the proportion of patients who can be treated with endocrine therapy alone by omitting chemotherapy in those with highly endocrine-sensitive disease. Eligible patients are randomized 1:1 to upfront surgery or neoadjuvant endocrine therapy with an aromatase inhibitor and ovarian function suppression. The primary endpoint is EFS. Secondary endpoints include overall survival, relapse-free survival, distant recurrrence-free survival, HR-QOL, the rate of endocrine therapy alone in adjuvant therapy, ET response rate in an Arm B, the rate of non-menopause and safety. A total of 950 patients will be enrolled. Randomization is stratified by cN0 vs cN1, HG1 or 2 vs 3, and institution. The JCOG2402 trial addresses an unmet need in adjuvant therapy of premenopausal HR-positive, HER2-negative breast cancer with intermediate risk and may contribute to the establishment of a new treatment strategy.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
950

participants targeted

Target at P75+ for phase_3 breast-cancer

Timeline
152mo left

Started Jan 2026

Longer than P75 for phase_3 breast-cancer

Geographic Reach
1 country

49 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress4%
Jan 2026Jan 2039

Study Start

First participant enrolled

January 28, 2026

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

June 22, 2026

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 26, 2026

Completed
11.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 27, 2038

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

January 27, 2039

Last Updated

July 8, 2026

Status Verified

June 1, 2026

Enrollment Period

12 years

First QC Date

June 22, 2026

Last Update Submit

July 4, 2026

Conditions

Keywords

Premenopausal womenHR+HER2-neoadjuvant endocrine therapy

Outcome Measures

Primary Outcomes (1)

  • Event free survival

    Time from randomization to the first diagnosis of local invasive recurrence, regional recurrence, distant recurrence, contralateral invasive breast cancer, inoperable progressive disease during neoadjuvant endocrine therapy, second primary invasive non-breast cancer (excluding non-melanoma skin cancer and in situ cervical cancer), or death from any cause

    Up to 12 years (5 years of accrual and 7 years of follow-up)

Secondary Outcomes (3)

  • Overall survival

    Up to 12 years (5 years of accrual and 7 years of follow-up)

  • Relapse-free survival

    Up to 12 years (5 years of accrual and 7 years of follow-up)

  • Distant recurrence-free survival

    Up to 12 years (5 years of accrual and 7 years of follow-up)

Study Arms (2)

Upfront surgery (Arm A)

ACTIVE COMPARATOR

Participants in Arm A will undergo breast surgery and adjuvant systemic treatment.

Drug: Adjuvant systemic therapy based on pathological findings

Neoadjuvant endocrine therapy (Arm B)

EXPERIMENTAL

Participants in Arm B will receive neoadjuvant endocrine therapy of aromatase inhibitor and OFS for three months, followed by breast surgery.

Drug: Adjuvant systemic therapy based on pathological findings and ET response

Interventions

If patients with Oncotype DX RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients) have an ET response (Ki-67 ≤10%), they are treated with endocrine therapy plus OFS without chemotherapy. Patients without an ET response or with high risk (RS ≧26) receive chemotherapy and endocrine therapy with OFS. Patients with RS ≤ 15 (pN0) are treated with tamoxifen. Adjuvant chemotherapy for pN0 and pN1 is TC and anthracycline-taxane, respectively. Aromatase inhibitor or tamoxifen is co-administered with a LHRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of LHRH agonist and dosing schedule is per investigator's discretion. Endocrine treatment beyond 5 years is at the investigator's discretion.

Neoadjuvant endocrine therapy (Arm B)

Patients with Oncotype DX recurrence score (RS) ≧16 (pN0) or pN1 are treated with chemotherapy and endocrine therapy with ovarian function suppression (OFS). Adjuvant chemotherapy for pN0 and pN1 is TC and anthracycline-taxane, respectively. Aromatase inhibitor or tamoxifen co-administered with a LHRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of LHRH agonist and dosing schedule is per investigator's discretion. Endocrine treatment beyond 5 years is at the investigator's discretion. Patients with RS ≤ 15 are treated with tamoxifen.

Upfront surgery (Arm A)

Eligibility Criteria

Age18 Years+
Sexfemale(Gender-based eligibility)
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Women aged 18 years or older
  • ECOG PS 0-1
  • HR-positive/HER2-negative breast cancer
  • ER expression ≥ 10%
  • cN0; HG 1: 3 cm\<T≤5 cm, HG 2: 2 cm\<T≤5 cm or HG3: 1 cm\<T≤5 cm cN1; cT\<5 cm and HG 1/HG 2
  • Premenopausal women with spontaneous menses within 12 months
  • No distant metastasis of breast cancer
  • No prior diagnosis of breast cancer.
  • No multiple regions of breast cancer
  • No contralateral breat cancer
  • Adequate organ function

You may not qualify if:

  • Presence of active double cancer (synchronous malignancy requiring treatment).
  • Ongoing infectious disease requiring systemic therapy. Fever ≥38.0°C at the time of registration.
  • Women who are pregnant, possibly pregnant, within 28 days postpartum, or breastfeeding; men whose partners intend to become pregnant.
  • Psychiatric illness or symptoms that interfere with daily living and may compromise trial participation.
  • Ongoing systemic administration (oral or IV) of steroids equivalent to ≥10 mg/day of prednisolone or other immunosuppressive agents.
  • Unstable angina (developed or worsened within the past 3 weeks) or myocardial infarction within the past 6 months.
  • Uncontrolled hypertension.
  • Uncontrolled diabetes mellitus despite continuous insulin or oral antidiabetic therapy.
  • Positive for HBs antigen or HCV antibodies (Patients positive for HCV antibodies are not excluded if HCV-RNA is undetectable.)
  • Positive for HIV antibodies (HIV testing is not mandatory.)
  • Presence of interstitial pneumonia, pulmonary fibrosis, or severe emphysema as diagnosed by chest CT.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (49)

Akita University Hospita

Akita, Japan

RECRUITING

Chiba Cancer Center

Chiba, Japan

RECRUITING

National Hospital Organization Kyushu Cancer Center

Fukuoka, Japan

RECRUITING

Fukushima Medical University Hospital

Fukushima, Japan

RECRUITING

National Hospital Organization Fukuyama Medical Center

Fukuyama, Japan

RECRUITING

Hamamatsu University School of Medicine

Hamamatsu, Japan

NOT YET RECRUITING

Kansai Medical University Hospital

Hirakata, Japan

RECRUITING

Hiroshima City North Medical Center Asa Citizens Hospital

Hiroshima, Japan

RECRUITING

Hiroshima University Hospital

Hiroshima, Japan

RECRUITING

Ibaraki Prefectural Central Hospital

Ibaraki, Japan

RECRUITING

Tokai University Hospital

Isehara, Japan

RECRUITING

Social medical corporation Hakuaikai Sagara Hospital

Kagoshima, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa, Japan

RECRUITING

Saitama Medical Center

Kawagoe, Japan

RECRUITING

Kitakyushu Municipal Medical Center

Kitakyushu, Japan

RECRUITING

National Hospital Organization Kure Medical Center

Kure, Japan

RECRUITING

Gunma University Hospital

Maebashi, Japan

RECRUITING

National Hospital Organization Shikoku Cancer Center

Matsuyama, Japan

RECRUITING

Aichi Cancer Center

Nagoya, Japan

RECRUITING

Nagoya City University

Nagoya, Japan

RECRUITING

Nagoya University Hospital

Nagoya, Japan

RECRUITING

NHO Nagoya Medical Center

Nagoya, Japan

RECRUITING

Niigata Cancer Center Hospital

Niigata, Japan

RECRUITING

National Hospital Organization Osaka National Hospital

Osaka, Japan

RECRUITING

Osaka International Cancer Institute

Osaka, Japan

NOT YET RECRUITING

National Hospital Organization Nagasaki Medical Center

Ōmura, Japan

RECRUITING

Gunma Prefectural Cancer Center

Ōta-ku, Japan

RECRUITING

Kitasato University Hospital

Sagamihara, Japan

RECRUITING

Saitama Cancer Center

Saitama, Japan

RECRUITING

Kindai University Hospital

Sakai, Japan

RECRUITING

Hokkaido Cancer Center

Sapporo, Japan

RECRUITING

Tohoku University Hospital

Sendai, Japan

RECRUITING

Shizuoka Cancer Center

Shizuoka, Japan

RECRUITING

Shizuoka General Hospital

Shizuoka, Japan

RECRUITING

Institute of Science Tokyo Hospital

Tokyo, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, Japan

RECRUITING

National Center for Global Health and Medicine

Tokyo, Japan

RECRUITING

National Hospital Organization Tokyo Medical Center

Tokyo, Japan

RECRUITING

Showa Medical University Hospital

Tokyo, Japan

RECRUITING

St.Luke's International Hospital

Tokyo, Japan

RECRUITING

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Tokyo, Japan

RECRUITING

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Tokyo, Japan

RECRUITING

Tokyo Women's Medical University Hospital

Tokyo, Japan

NOT YET RECRUITING

Toranomon Hospital

Tokyo, Japan

RECRUITING

Mie University Hospital

Tsu, Japan

RECRUITING

Tsukuba University Hospital

Tsukuba, Japan

RECRUITING

Yamaguchi University Hospital

Ube, Japan

RECRUITING

Yao Municipal Hospital

Yao, Japan

RECRUITING

Kanagawa Cancer Center

Yokohama, Japan

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Central Study Contacts

Makiko Ono, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

June 22, 2026

First Posted

June 26, 2026

Study Start

January 28, 2026

Primary Completion (Estimated)

January 27, 2038

Study Completion (Estimated)

January 27, 2039

Last Updated

July 8, 2026

Record last verified: 2026-06

Locations