Metastasis-directed Therapy for Oligometastases of Breast Cancer

NCT06135714 | Recruiting Phase 3 DMC

• 1 other identifier: JCOG2110
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 1

Brief Summary

OLIGAMI trial is a multi-institutional, two-arm, open-label, randomized controlled phase III trial being conducted with the participation of 50 hospitals belonging to Japan Clinical Oncology Group. After the first registration, all patients will be performed in a 12-week, subtype-specific, systemic therapy consisting of CDK4/6 inhibitors with hormonal therapy for luminal BC, docetaxel with trastuzumab and pertuzumab for HER2-positive BC, chemotherapy with immune checkpoint inhibitors for triple-negativeBC expressing PD-L1, and olaparib for cases harboring BRCA mutations. For other triple-negative BC, chemotherapy will be administered. If this 12-week systemic therapy does not cause any progression or complete response, patients proceed to second registration for randomization; arm A continues same systemic therapy alone, and arm B performs MDT followed by same systemic therapy. The MDT will involve either RT or surgery, and RT will involve mainly SBRT and partly conventional RT.

Conditions

Metastatic Breast Cancer; Breast Cancer; Oligometastasis

Keywords

SBRT; Surgery; Stereotactic Body Radiation Therapy; Metastasis-directed Therapy

Outcome Measures

Primary Outcomes (1)

• Overall survival after second registration

  5 years

Secondary Outcomes (7)

• Overall survival after primary registration

  5 years

• Progression-free survival

  5 years

• Progression site (oligometastasis, lesion other than oligometastasis)

  5 years

• Oligometastatic progression-free survival for each definitive local therapy (group B only)

  5 years

• Adverse event rate

  5 years

Study Arms (2)

Arm A: Standard of care

PLACEBO COMPARATOR

Continuation of systemic drug therapy.

Drug: Systemic therapy for 12 weeks after primary registration; Drug: Same systemic therapy after secondary registration

Arm B: Metastasis-directed therapy followed by Standard of care

EXPERIMENTAL

Metastasis-directed therapy (radiation or surgery for oligometastasis) + systemic drug therapy.

Drug: Systemic therapy for 12 weeks after primary registration; Procedure: Radiation therapy (SBRT/conventional RT); Procedure: Surgery; Drug: Same systemic therapy after secondary registration

Interventions

Same systemic therapy after secondary registration DRUG

* Luminal BC 1. Denovo stage IV Premenopausal(PRE): Aromatase inhibitor(AI) + CDK4/6 inhibitor(CDK) +LHRH agonist, or Fulvestrant(FUL) + CDK4/6 inhibitor +LHRH agonist Postmenopausal(POST): AI + CDK 2. Recurrence after completion of postoperative endocrine therapy PRE: AI + CDK +LHRH agonist, or FUL + CDK +LHRH agonist POST: AI + CDK, or FUL + CDK 3. Recurrence during postoperative endocrine therapy PRE: FUL + CDK +LHRH agonist, or AI + CDK +LHRH agonist POST: FUL + CDK * HER2-positive BC Pertuzumab + Trastuzumab + Taxane (docetaxel or paclitaxel) ・Triple negative BC. 1. PD-L1 negative - following a) or b) 1. Taxane (naive for taxane) 2. S-1 or Capecitabine or Eriblin (previously treated with taxane) 2. PD-L1 positive - following a) or b) 1. Pembrolizumab + Gemcitabine + Carboplatin 2. Atezolizumab + Nab-paclitaxel 3. BRCA-mutation positive Olaparib

Arm A: Standard of care; Arm B: Metastasis-directed therapy followed by Standard of care

Systemic therapy for 12 weeks after primary registration DRUG

* Luminal BC 1. Denovo stage IV Premenopausal(PRE): Aromatase inhibitor(AI) + CDK4/6 inhibitor(CDK) +LHRH agonist, or Fulvestrant(FUL) + CDK4/6 inhibitor +LHRH agonist Postmenopausal(POST): AI + CDK 2. Recurrence after completion of postoperative endocrine therapy PRE: AI + CDK +LHRH agonist, or FUL + CDK +LHRH agonist POST: AI + CDK, or FUL + CDK 3. Recurrence during postoperative endocrine therapy PRE: FUL + CDK +LHRH agonist, or AI + CDK +LHRH agonist POST: FUL + CDK * HER2-positive BC Pertuzumab + Trastuzumab + Taxane (docetaxel or paclitaxel) ・Triple negative BC. 1. PD-L1 negative - following a) or b) 1. Taxane (naive for taxane) 2. S-1 or Capecitabine or Eriblin (previously treated with taxane) 2. PD-L1 positive - following a) or b) 1. Pembrolizumab + Gemcitabine + Carboplatin 2. Atezolizumab + Nab-paclitaxel 3. BRCA-mutation positive Olaparib

Arm A: Standard of care; Arm B: Metastasis-directed therapy followed by Standard of care

Radiation therapy (SBRT/conventional RT) PROCEDURE

Brain: 18-24Gy/1Fr. or 27Gy/3Fr. or 30Gy/5Fr. Lung: 42Gy/4Fr.(peripheral) or 50Gy/8Fr.(central) or 60Gy/25Fr.(ultra central) Liver/Adrenal: 40Gy/5Fr. Bone: 35Gy/5Fr. Distant lymph node: 45/10Fr. or 60Gy/25Fr.

Arm B: Metastasis-directed therapy followed by Standard of care

Surgery PROCEDURE

Surgery for the oligometastases

Arm B: Metastasis-directed therapy followed by Standard of care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Active malignancies curatively treated with no evidence of disease for \>= 5 years prior to randomization.
• Infection with care.
• Fever up 38 degrees Celsius.
• Childbearing potential, delivery after 28 days, breastfeeding
• Mental disorders.
• Continuously take steroids or immunosuppressive drugs.
• Unstable angina or history of cardiac infarction within 6months.
• Uncontrolled Hypertension.
• Uncontrolled Diabetes mellitus.
• Congestive heart failure deserved class II of New York Heart Association (NYHA), uncontrolled Dilated or Hypertrophic cardiomyopathy.
• Severe arrhythmia need to cure (except Atrial fibrillation, Paroxysmal supraventricular tachycardia)
• Interstitial pneumonia, pulmonary fibrosis, severe emphysema diagnosed chest CT scan.
• HBs Ag+

Sponsors & Collaborators

• Tokyo Medical and Dental University: lead

Study Sites (1)

Tokyo Medical and Dental Univetsity

Tokyo, Tokyo, 1138510, Japan

RECRUITING

Related Publications (1)

• Sasaki K, Ishiba T, Nishibuchi I, Hara F, Sekino Y, Machida R, Shibata T, Kawahara D, Sagara Y, Naito Y, Terata K, Ozaki Y, Shimomura A, Sakai T, Shigematsu H, Sudo K, Nozawa K, Yoshimura M, Shikama N, Mizowaki T, Shien T. A randomized controlled trial of metastasis-directed therapy for oligometastases in breast cancer: OLIGAMI trial (JCOG2110). Jpn J Clin Oncol. 2026 Jan 30:hyag019. doi: 10.1093/jjco/hyag019. Online ahead of print.

  PMID: 41615067 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Radiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Toshiyuki Ishiba, M.D.Ph.D.

  Tokyo Medical and Dental University

  PRINCIPAL INVESTIGATOR

• Tadahiko Shien, M.D.Ph.D.

  Okayama University

  STUDY CHAIR

• Ikuno Nishibuchi, M.D.Ph.D.

  Hiroshima University

  PRINCIPAL INVESTIGATOR

• Fumitaka Hara, M.D.Ph.D.

  The Cancer Institute Hospital of Japanese Foundation for Cancer Research

  PRINCIPAL INVESTIGATOR

• Naoto Shikama, M.D.Ph.D.

  Juntendo University

  STUDY CHAIR

Central Study Contacts

Tohiyuki Ishiba, M.D.Ph.D.

CONTACT

+81-3-5803-2101; ishsrg2@tmd.ac.jp

Ikuno Nishibuchi, M.D.Ph.D.

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: Assistant professor

Model Details: If this 12-week systemic therapy does not cause any progression or complete response, patients proceed to second registration for randomization; arm A continues same systemic therapy alone, and arm B performs MDT followed by same systemic therapy. The MDT will involve either RT or surgery, and RT will involve mainly SBRT and partly conventional RT.

Study Record Dates

• First Submitted: November 13, 2023
• First Posted: November 18, 2023
• Study Start: November 8, 2023
• Primary Completion (Estimated): November 8, 2026
• Study Completion (Estimated): October 31, 2032
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF

Locations

JP (1)