Evaluating the Response-Guided Therapy With Neoadjuvant Endocrine Therapy to Optimize Adjuvant Treatment in Premenopausal HR+/HER2- Breast Cancer (JCOG2402, Young HOPE)

Official title

A Randomized Phase III Study of Response-Guided Therapy Following Neoadjuvant Endocrine Therapy to Optimize Adjuvant Treatment in Premenopausal HR+/HER2- Breast Cancer (JCOG2402, Young HOPE)

Overview

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.

Interventions

• Drug Adjuvant systemic therapy based on pathological findings and ET response
  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-administe
• Drug Adjuvant systemic therapy based on pathological findings
  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 i

Primary outcome measures

• Event free survival [Time frame: Up to 12 years (5 years of accrual and 7 years of follow-up)]

Secondary outcome measures (3)

• Overall survival [Time frame: Up to 12 years (5 years of accrual and 7 years of follow-up)]
• Relapse-free survival [Time frame: Up to 12 years (5 years of accrual and 7 years of follow-up)]
• Distant recurrence-free survival [Time frame: Up to 12 years (5 years of accrual and 7 years of follow-up)]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 49 centers

• Akita University Hospita — Akita
• Chiba Cancer Center — Chiba
• National Hospital Organization Kyushu Cancer Center — Fukuoka
• Fukushima Medical University Hospital — Fukushima
• National Hospital Organization Fukuyama Medical Center — Fukuyama
• Hamamatsu University School of Medicine — Hamamatsu
• Kansai Medical University Hospital — Hirakata
• Hiroshima City North Medical Center Asa Citizens Hospital — Hiroshima
• … and 41 more centers

Identifiers

NCT: NCT07671885 · JCOG2402 · jRCTs031250687

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗