JCOG1806: Avoid mastectomy using trastuzumab, pertuzumab and radiation study for breast cancer

JRCT ID: jRCTs031190129

Registered date:05/11/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Clinical T1-2N0M0, HER2 positive primary breast cancer
• Date of first enrollment: 11/11/2019
• Target sample size: 350
• Study type: Interventional

Intervention(s)

Anti-HER2 therapy and chemotherapy is performed for clinical cT1-2N0M0 HER2 positive primary breast cancer.

Primary chemotherapy + anti-HER2 therapy
(1) AC/EC therapy + THP therapy
AC/EC therapy (anthracycline + cyclophosphamide) followed by THP therapy ( taxane + trastuzumab + pertuzumab)
AC/EC therapy; q3w (every 3 week) as 1cycle, perform 3 or 4 cycles.
THP therapy; q3w (every 3 week) as 1cycle, perform 3 or 4 cycles.
(2) TCHP therapy
Docetaxel + carboplatin + trastuzumab + pertuzumab
q3w (every 3 week) as 1cycle, perform 5 or 6 cycles.
(3) PacHP therapy
Paclitaxel + trastuzumab + pertuzumab
Q1w (every 1 week, Dya1,8,15 ) as 1cycle, 3 or 4 cycles.

Additional anti-HER2 therapy + radiation therapy +/- endocrine therapy
Diagnosed clinical Complete Response (cCR) after primary chemotherapy + anti-HER2 therapy, additional anti-HER2 therapy (trastuzumab + pertuzumab; HP therapy) + radiation therapy are performed.
(1) Additional anti-HER2 therapy
Perform HP therapy every 3 week, up to total 18 cycles.
(2) Radiation therapy
Total breast irradiation; total 50Gy/25Fr, or 42.56Gy/16Fr.
Boost; 16Gy/8Fr.
(3) Endocrine therapy
Patients with either ER-positive or PgR-positive by IHC analysis receive the following endocrine therapy for 5 years depending on the menopausal status.
A) Tamoxifen + LH-RH agonist
B) Tamoxifen
C) Aromatase inhibitor

Surgery
When the efficacy judgment after initial drug therapy does not correspond to cCR and it does not worsen during initial drug therapy, surgery is performed. Breast-conserving surgery or total mastectomy is performed as breast surgery, and sentinel lymph node biopsy or axillary lymph node dissection is performed on axillary lymph nodes.

Outcome(s)

• Primary Outcome: 3 year survival rate with no distant metastasis
• Secondary Outcome: Distant Free Survival rate, OverAll Survival rate, Recurrence free survival, Breast-operation free survival rate, Local recurrence rate, Cosmetic change rate, Adverse event rate, non-CR match rate

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 74age old
• Gender: Female

Include criteria

(1) Histologically documented as invasive ductal carcinoma of breast.
(2)Histologically documented as
1. ER and PR receptors are investigated via IHC analysis.
2. HER2 positivity is defined as either of the following local laboratory assessment: In situ hybridization (ISH) -amplified (ratio of HER2 to CEP17 > 2.0 or singleprobe average HER2 gene copy number >6 signals/cell), or IHC 3+
(3) In primary resion, breast sonography and breast MRI meet the following,
1. Diameter defined all modality is under 5cm
2. There are no multiple lesions in the ipsilateral breast
(4) No axillary LN metastasis is defined by sonography,
(5) No distant metastasis defined as
1. Chest ; Chest CT or FDG-PET/CT or FDG-PET/MRI
2. Abdomen ; Abdomen CT or FDG-PET/CT or FDG-PET/MRI
3. Bone ; Bone Scan or FDG-PET/CT or FDG-PET/MRI
4. Brain ; no need to explain with no symptom.
(6) No Bilateral breast cancer
(7) Women aged 20-74 years
(8) ECOG performance status of 0 or 1
(9) A measurable lesion is not required.
(10) Previously treatments are followed,
1. No prior chemotherapy or targeted systemic therapy for other cancer within 5years.
2. No prior radiation therapy within the breast, chest-wall.
3. No prior anticancer drug treatment, endocrine therapy, or surgery for the purpose of treating breast cancer. Endocrine therapy for the purpose of alleviating menopausal symptoms, surgical biopsy or sentinel lymph node biopsy for diagnosis is allowed.
(11) Comorbidity is as,
1.No DCIS, invasive cancer.
2. No Scleroderma or systemic lupus erythematosus
3. No Li Fraumeni syndrome
(12) No BRCA mutation is evaluated.
(13) Both upper arms can be lifted in the supine position.
(14) Adequate hematologic and end-organ function, defined by the adequate laboratory results obtained within 28 days prior to the first enrollment .
1. ANC >= 1500 cells/mm3
2. Hemoglobin >= 9.0 g/dL (Patients are not transfused or receive erythropoietic treatment to meet this criterion.)
3. Platelet count >= 100,000/ mm3
4. Serum bilirubin <= 1.5 mg/dL
5.AST, ALT <= 100 U/L
6. Creatinine <= 1.2 mg/dL
(15) Ejection fraction of cardiac function is defined over 50%
(16) Signed Informed Consent Form

Exclude criteria

(1) Active malignancies curatively treated with no evidence of disease for >= 5 years prior to randomization.
(2) No MRI enforcement due to hypersensitivity of Gadolinium enhancement, Claustrophobia, metal-embedment.
(3) Infection with care.
(4) Fever up 38 degree.
(5) Childbearing potential, delivery after 28 days, breastfeeding
(6) Mental disorders.
(7) Continuously take steroids or immunosuppressive drugs.
(8) Poorly controlled Diabetes mellitus.
(9) Poorly controlled Hypertension.
(10) Unstable anjina or history of cardiac infarction within 6months.
(11) Congestive heart failure deserved class II of New York Heart Association(NYHA), poorly controlled Dilated or Hypertrophic cardiomyopathy.
(12) Severe arrhythmia need to cure (except Atrial fibrillation, Paroxysmal supraventricular tachycardia )
(13)Interstitial pneumonia, pulmonary fibrosis, severe emphysema diagnosed chest CT scan.
(14) HBs Ag+

Related Information

• Primary Sponsor: FUJISAWA Tomomi
• Source(s) of Monetary Support: National Cancer Center Japan