Metastasis-directed Therapy for Oligometastases of Breast Cancer

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

• Breast Cancer
• Oligometastasis
• Metastatic Breast Cancer

Interventions

DRUG

Systemic therapy for 12 weeks after primary registration

* 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

PROCEDURE

Radiation therapy (SBRT/conventional RT)

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.

PROCEDURE

Surgery

Surgery for the oligometastases

DRUG

Same systemic therapy after secondary registration

* 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

Sponsors & Collaborators

• Tokyo Medical and Dental University

  lead OTHER

Principal Investigators

• Toshiyuki Ishiba, M.D.Ph.D. · Tokyo Medical and Dental University

• Tadahiko Shien, M.D.Ph.D. · Okayama University

• Ikuno Nishibuchi, M.D.Ph.D. · Hiroshima University

• Fumitaka Hara, M.D.Ph.D. · The Cancer Institute Hospital of Japanese Foundation for Cancer Research

• Naoto Shikama, M.D.Ph.D. · Juntendo University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-11-08

Primary Completion

2026-11-08

Completion

2032-10-31

Countries

• Japan

Study Locations