NCT06135714

Metastasis-directed Therapy for Oligometastases of Breast Cancer

a Randomized Trial for OLIGo Metastases Breast cAncer With or Without Metastasis-dIrected Therapy

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 340 (estimated)
• Sponsor: Tokyo Medical and Dental University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

A brief background discussion: Oligometastases were initially described as a concept bridging localized disease with widespread distant metastases, but a consensus on its definition has yet to be reached. Recently, the term "metastasis-directed therapy" (MDT) was coined to encompass local therapy for distant metastases, including surgery and radiation therapy (RT), especially stereotactic body radiation therapy (SBRT). Though OLIGO-BC1 and SABR-COMET have indicated the potential benefits of MDT for oligometastases , NRG-BR002 revealed no significant difference in progression-free survival (PFS). As a definitive conclusion to this clinical question has not been reached, there is an increasing demand for phase III trials focusing on breast cancer (BC). We planned the JCOG2110, also called as OLIGAMI trial. Trial design: 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. Eligibility criteria: OLIGAMI trial will encompass all subtypes of advanced BC. The key criteria of the first registration are as follows: 1) Histologically diagnosed as invasive BC. Biopsy from oligometastases is desirable but not required. 2) Diagnosed with advanced BC with oligometastases by neck to pelvis enhanced CT, FDG-PET,and brain enhanced MRI. 3) Oligometastases defined as: (i) Maximum diameter of each tumor is 3 cm or less. (ii) Total number of 3 or less. (iii) In case of brain metastasis, maximum diameter is 2 cm or less and asymptomatic. 4) The patient with local recurrence is included. 5) De novo stage IV BC is included. The criteria of secondary registration are as follows: 1) The planned number of courses of systemic therapy has been performed. 2) No progression or new distant metastasis by response evaluation. 3) At least one oligometastasis remains. Specific Aims: OLIGAMI trial aims to confirm the superiority of MDT to systemic therapy for oligometastases of BC. The primary endpoint is overall survival (OS) after randomization, while the secondary endpoints include OS after first registration, PFS, progression site (oligometastases vs. non-oligometastases), PFS specifically related to MDT (restricted arm B), proportion of adverse events and serious adverse events, and the non-progression proportion of health-related quality of life. Statistical methods: The sample size was calculated as 268 to detect 12% of 5-year OS difference with a one-sided alpha of 0.05, power of 70%, 3 years of accrual, and 5 years of follow up. Therefore, we assumed the planned sample size for second registration for randomization as 270. We set the number of first registration as 340, assuming that there may be some patients with progression or complete response after the systemic therapy for 12 weeks. Present accrual and target accrual: The patient accrual will start in November 2023. Enrolment of 340 patients for first registration is planned over a 3-year accrual period.

Conditions

• Breast Cancer
• Oligometastasis
• Metastatic Breast Cancer

Interventions

Type	Name	Description
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

Timeline

• Start date: 2023-11-08
• Primary completion: 2026-11-08
• Completion: 2032-10-31
• First posted: 2023-11-18
• Last updated: 2026-02-11

Locations

1 site across 1 country: Japan