Metastasis-directed Therapy for Oligometastases of Breast Cancer

NCT ID: NCT06135714

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 340 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-08
• Study Completion Date: 2032-10-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Standard of care

Continuation of systemic drug therapy.

Group Type: PLACEBO_COMPARATOR

Systemic therapy for 12 weeks after primary registration

Intervention Type: 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

Same systemic therapy after secondary registration

Intervention Type: 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 B: Metastasis-directed therapy followed by Standard of care

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

Group Type: EXPERIMENTAL

Systemic therapy for 12 weeks after primary registration

Intervention Type: 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

Radiation therapy (SBRT/conventional RT)

Intervention Type: 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.

Surgery

Intervention Type: PROCEDURE

Surgery for the oligometastases

Same systemic therapy after secondary registration

Intervention Type: 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

Interventions

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

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Surgery

Surgery for the oligometastases

Intervention Type: PROCEDURE

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

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

1. Active malignancies curatively treated with no evidence of disease for >= 5 years prior to randomization.

2. Infection with care.

3. Fever up 38 degrees Celsius.

4. Childbearing potential, delivery after 28 days, breastfeeding

5. Mental disorders.

6. Continuously take steroids or immunosuppressive drugs.

7. Unstable angina or history of cardiac infarction within 6months.

8. Uncontrolled Hypertension.

9. Uncontrolled Diabetes mellitus.

10. Congestive heart failure deserved class II of New York Heart Association (NYHA), uncontrolled Dilated or Hypertrophic cardiomyopathy.

11. Severe arrhythmia need to cure (except Atrial fibrillation, Paroxysmal supraventricular tachycardia)

12. Interstitial pneumonia, pulmonary fibrosis, severe emphysema diagnosed chest CT scan.

13. HBs Ag+

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tokyo Medical and Dental University

OTHER

Sponsor Role: lead

Responsible Party

Toshiyuki Ishiba, M.D.Ph.D.

Assistant professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Toshiyuki Ishiba, M.D.Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Tokyo Medical and Dental University

Tadahiko Shien, M.D.Ph.D.

Role: STUDY_CHAIR

Okayama University

Ikuno Nishibuchi, M.D.Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Hiroshima University

Fumitaka Hara, M.D.Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Naoto Shikama, M.D.Ph.D.

Role: STUDY_CHAIR

Juntendo University

Locations

Tokyo Medical and Dental Univetsity

Tokyo, Tokyo, Japan

Site Status: RECRUITING

Countries

Japan

Central Contacts

Tohiyuki Ishiba, M.D.Ph.D.

Role: CONTACT

ishsrg2@tmd.ac.jp

+81-3-5803-2101

Ikuno Nishibuchi, M.D.Ph.D.

Role: CONTACT

Facility Contacts

Tohiyuki Ishiba

Role: primary

ishsrg2@tmd.ac.jp

+81-3-5803-2101

Related Links

https://jcog-breast.com/report/now/jcog2110/

Related Info

Other Identifiers

JCOG2110

Identifier Type: -

Identifier Source: org_study_id