Trial Title:
Metastasis-directed Therapy for Oligometastases of Breast Cancer
NCT ID:
NCT06135714
Condition:
Breast Cancer
Oligometastasis
Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Neoplasm Metastasis
Conditions: Keywords:
SBRT
Surgery
Stereotactic Body Radiation Therapy
Metastasis-directed Therapy
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Systemic therapy for 12 weeks after primary registration
Description:
- 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 group label:
Arm A: Standard of care
Arm group label:
Arm B: Metastasis-directed therapy followed by Standard of care
Intervention type:
Procedure
Intervention name:
Radiation therapy (SBRT/conventional RT)
Description:
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 group label:
Arm B: Metastasis-directed therapy followed by Standard of care
Intervention type:
Procedure
Intervention name:
Surgery
Description:
Surgery for the oligometastases
Arm group label:
Arm B: Metastasis-directed therapy followed by Standard of care
Intervention type:
Drug
Intervention name:
Same systemic therapy after secondary registration
Description:
- 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 group label:
Arm A: Standard of care
Arm group label:
Arm B: Metastasis-directed therapy followed by Standard of care
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.
Criteria for eligibility:
Criteria:
Primary Registration Eligibility Criteria:
1. Histologically diagnosed as invasive breast cancer. Biopsy from oligometastasis is
desirable but not required.
2. Histologically proven positive/negative for ER, PgR, and HER2, and classified as
luminal, HER2-positive, or TN breast cancer.
3. One of the following <1> to <4>; <1>In case of no history of breast cancer in the
past, either (i) or (ii) below.
(i) Unilateral noninvasive breast cancer at registration, diagnosed as invasive
breast cancer by biopsy from oligometastasis (ii) Unilateral invasive breast cancer
at registration <2>In case of having a history of mastectomy or breast-conserving
surgery for unilateral noninvasive breast cancer, either (i) or (ii) below. (i)
Absence of breast/chest wall tumor at registration and diagnosed as invasive breast
cancer by biopsy from oligometastasis (ii) Unilateral invasive breast cancer at
registration (whether ipsilateral or contralateral to previous breast cancer) <3>In
case of having a history of mastectomy or breast-conserving surgery for unilateral
invasive breast cancer, either (i) or (ii) below. (i) Absence of breast/chest wall
tumor at registration (ii) Ipsilateral invasive/noninvasive breast cancer to
previous breast cancer at registration and diagnosed as recurrence <4>In case of
having a history of mastectomy or breast-conserving surgery for unilateral
noninvasive breast cancer and contralateral invasive breast cancer, no breast/chest
wall tumor at registration.
4. Diagnosed with advanced breast cancer with oligometastasis by neck to pelvis
enhanced CT, FDG-PET (PET/CT), and brain enhanced MRI.
5. oligometastasis 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.
6. No distant metastasis other than oligometastasis.
7. Metastasis-directed therapy (radiation or surgery) is considered feasible for all
oligometastases.
8. In case of bone metastasis, none of the following:
(i) Metastasis of three consecutive vertebral bodies (ii) Spinal metastasis
extending into the spinal canal (Bilsky grade is 1b or higher) (iii) Long bone
metastasis extending to the femoral head, neck, and trochanter (iv) Long bone
metastasis with more than 1/3 of bone cortical defects (v) Severe pain uncontrolled
with drugs.
9. Aged 18-80 years.
10. ECOG performance status of 0 or 1.
11. A measurable lesion is not required.
12. No history of surgery, drug therapy, or radiotherapy for distant metastasis.
Bisphosphonate preparations and RANKL inhibitors before registration, and surgery
for the purpose of diagnosing metastasis are permitted.
13. No radical surgery of the primary tumor or regional lymph nodes between diagnosis of
oligometastasis to registration.
14. In the case of recurrent breast cancer, disease-free interval of 12 months or more
from surgery, perioperative chemotherapy, or molecular targeted therapy for initial
treatment of breast cancer.
15. No prior treatment of endocrine therapy, chemotherapy, molecular targeted therapy,
and immunotherapy against any other malignancies within 5 years.
16. Adequate organ function within 14 days prior to the first registration. (i) ANC >=
1500 cells/mm3 (ii) Hemoglobin >= 9.0 g/dL (iii) Platelet count >= 100,000/ mm3 (iv)
Serum bilirubin <= 1.5 mg/dL (v) AST <= 100 U/L (vi) ALT <= 100 U/L (vii) Creatinine
<= 1.5 mg/dL (<= 2.3 mg/dL for luminal breast cancer)
17. Ejection fraction of cardiac function is defined over 50%.
18. Written informed consent.
Secondary Registration Eligibility Criteria:
1. Primary registration in this study, and the planned number of courses of systemic
drug therapy by subtype has been performed.
2. No progression or new distant metastasis by response evaluation.
3. Secondary registration is within 28 days from response evaluation.
4. Within 84-126 days from the primary registration.
5. At least one oligometastasis remains on imaging and considered feasible to
definitive local therapy.
6. No metastasis-directed therapy for breast cancer after primary registration.
7. ECOG performance status of 0 or 1.
8. Adequate organ function within 14 days prior to the second registration. (i) ANC >=
1500 cells/mm3 (ii) Hemoglobin >= 9.0 g/dL (iii) Platelet count >= 100,000/ mm3 (iv)
Serum bilirubin <= 1.5 mg/dL (v) AST <= 100 U/L (vi) ALT <= 100 U/L (vii) Creatinine
<= 1.5 mg/dL (<= 2.3 mg/dL for luminal breast cancer)
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+
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tokyo Medical and Dental Univetsity
Address:
City:
Tokyo
Zip:
1138510
Country:
Japan
Status:
Recruiting
Contact:
Last name:
Tohiyuki Ishiba
Phone:
+81-3-5803-2101
Email:
ishsrg2@tmd.ac.jp
Start date:
November 8, 2023
Completion date:
October 31, 2032
Lead sponsor:
Agency:
Tokyo Medical and Dental University
Agency class:
Other
Source:
Tokyo Medical and Dental University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06135714
