JBCRG-M10 (INDUCE trial)

JRCT ID: jRCTs041240039

Registered date:04/06/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: PD-L1-positive, hormone receptor-negative, HER2-negative inoperable or recurrent breast cancer
• Date of first enrollment: 04/06/2024
• Target sample size: 106
• Study type: Interventional

Intervention(s)

1. Induction therapy arm
Induction therapy is given in cycles 1 and 2: PTX 90 mg/m2 on days 1, 8 and 15 and bevacizumab 10 mg/kg intravenously on days 1 and 15 for a cycle of 28 days. Cycle 3 and after, a 28-day cycle of atezolizumab 840 mg on days 1 and 15 and nab-PTX 100 mg/m2 on days 1, 8, and 15 is administered intravenously. A series of treatment consists of 2 cycles of induction therapy + immunochemotherapy.

- Efficacy and safety of the induction therapy arm will be evaluated as a treatment strategy including 2 cycles of induction therapy.
2. Standard therapy arm
Patients receive atezolizumab 840 mg on days 1 and 15 and nab-PTX 100 mg/m2 intravenously on days 1, 8 and 15 for a cycle of 28 days.

Outcome(s)

Primary Outcome

Primary endpoint
(1)Progression free survival

Key secondary endpoints
(1)2-year PFS rate
(2)2-year PFS rate of non-PD patients with initial imaging evaluation in induction therapy group
Compare and evaluate standard therapy group and induction therapy group.

Secondary Outcome

(1)Safety
(2)Overall response rate
(3)Overall survival
(4)Disease control rate

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Diagnosis of metastatic recurrence or unresectable advanced TNBC.
(2) PD-L1 positivity (SP142 IC>=1) confirmed at each institution using the most recently collected or stored tumor specimen.
(3) Patients for whom curative treatment was indicated have had a disease progression from completion of curative treatment (date of surgery for primary breast cancer or date of last administration of perioperative drug therapy [including anthracycline regimen, taxane regimen, anti-PD-(L)1 antibody, capecitabine, PARP inhibitor, etc.], whichever is later) to the first local or distant recurrence has elapsed for at least 6 months. The date of postoperative radiation therapy is not included in this calculation. The use of anti-PD-(L)1 antibodies for perioperative pharmacotherapy is acceptable.
(4) ECOG PS 0-1
(5)Age is 18 years or older, female or male.
(6)Patients with histologically or cytologically confirmed TNBC and confirmed ER negative (positive cell occupancy <10% or Allred Proportion score 0-2) and HER2 negative (IHC 1+ or less or FISH/DISH negative) according to ASCO/CAP criteria 2018 (In the case of IHC 2+, the patient must be confirmed to be negative by FISH/DISH.)
(7) Patients who have not received chemotherapy for metastatic recurrence or unresectable advanced cancer. However, previous administration of PARP inhibitors for metastatic recurrence or unresectable advanced cancer in patients with BRCA gene pathological variants is acceptable.
(8) Have measurable or unmeasurable disease as assessed by CT or MRI at the implementing institution. Tumor lesions located in previously irradiated areas are considered evaluable lesions if there is clear progression after irradiation.
(9) Laboratory tests performed within 14 days prior to registration meet the following 1) to 8). However, the patient must not have received granulocyte colony stimulating factor (G-CSF product) administration or blood transfusion within 14 days prior to the date of blood collection.
1) Neutrophil count >= 1500 / mm3
2) Platelet count >=10 x 104 / mm3
3) Hemoglobin >=8.0 g/dL
4) AST (GOT) <=100 IU/L (<=200 IU/L in case of liver metastasis)
5) ALT (GPT) <=100 IU/L (<=200 IU/L in case of liver metastasis)
6) Total bilirubin <= 1.5 mg/dL
Total bilirubin < 3.0 mg/dL for Gilbert's syndrome
7) Creatinine <= 1.5 mg/dL
8) One of the following is met
i) Negative (-) or 1+ urine protein (test paper method)
ii) Urine protein (test paper method) is 2+ or higher; 24-hour urine protein measurement and urine protein <= 1 g /24 hours (urine protein to creatinine ratio <= 1 can be used as a substitute)
(10)Blood pressure is adequately controlled (systolic blood pressure less than 150 mmHg and diastolic blood pressure less than 90 mmHg with less than 2 antihypertensive drugs (counted by the number of combination)).
(11)Patients are expected to survive for at least 3 months.
(12)Written consent has been obtained from the patient after a full explanation of the study contents has been given prior to enrollment.
(13)For women of childbearing potential (including patients who are not menstruating for medical reasons such as chemical menopause), consent to continued contraception until 5 months after the last dose of atezolizumab or 6 months after the last dose of bevacizumab, nabPTX or PTX, whichever is later. Patients who also agree not to breastfeed during study treatment for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab. For males, patients whose partners agree to remain contraceptive until 6 months after the last dose of PTX or nab-PTX, whichever comes later, if their partners are likely to become pregnant.

Exclude criteria

(1) Active brain metastases or cancerous meningitis. Treatment proven brain metastases are acceptable if neurologic symptoms have recovered to baseline and are clinically stable for at least 2 weeks prior to enrollment.
(2) Patients with a history of invasive malignancy within the past 3 years prior to enrollment. However, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (intraepithelial carcinoma) or intramucosal carcinoma equivalent that is considered curable with local treatment shall not be included as active overlapping cancer.
(3) Simultaneous or heterochronic bilateral invasive breast cancer. However, bilateral TNBC and PD-L1 positivity confirmed by evaluation of specimens from recurrent lesions are acceptable.
(4) Patients who have received radiotherapy within 14 days prior to registration. (Administration or irradiation on the same day of the week 14 days prior to enrollment is acceptable.)
(5) Patients receiving any other study drug within 14 days prior to enrollment. (Administration on the same day of the week 14 days prior to enrollment is allowed.)
(6) Patients who have received a live vaccine within 30 days of the first dose of study drug. Inactivated vaccines are acceptable.
(7) Patients who have received systemic corticosteroids or immunosuppressive drugs exceeding 10 mg/day prednisone equivalent within 14 days prior to enrollment for active autoimmune disease. (Temporary administration for the purpose of testing or prophylactic administration is excluded.)
(8) Patients with active infections requiring systemic treatment.
(9) Patients with interstitial lung disease/pulmonary inflammation or a history of interstitial lung disease/pulmonary inflammation requiring systemic corticosteroid administration at the time of registration. (A history of radiation pneumonitis [fibrosis] within the radiation field is acceptable.)
(10) Pregnant, possibly pregnant, or lactating patients.
(11)HBs antigen-positive or HCV antibody-positive patients; HCV antibody-positive patients with HCV viral load below the detection limit are acceptable.
(12)Patients positive for either HIV-1 or HIV-2 antibodies (testing not required for registration).
(13)Patients with significant cardiovascular disease. Patients who have undergone myocardial infarction, acute coronary artery disease, or coronary angioplasty/stenting/bypass surgery within the past 6 months; patients with New York Heart Association classification class III-IV congestive heart failure.
(14)Patients with the following pre-existing medical conditions/comorbidities.
1) Poorly controlled diabetes mellitus
2)Peripheral sensory neuropathy of Grade 2 or higher
3) Congenital bleeding or coagulopathy
4)Arterial thromboembolism (cerebral infarction, etc.) or venous thromboembolism (deep vein thrombosis, pulmonary embolism, etc.) within 6 months prior to registration
5)Perforation of the gastrointestinal tract, active gastrointestinal ulcer, Grade 3 or higher bleeding (site not specified)
6) Other serious complications (renal failure, liver failure, etc.)
(15) Patients with a history or complication of any disease, treatment history, or laboratory abnormality that may affect study results, interfere with the patient's ability to complete the study, or make the patient's participation in the study infeasible for the patient's benefit.
(16) Patients with psychiatric disorders that may affect the conduct of the study.
(17) Patients with a history of hypersensitivity to the study drug or its analogues.
(18) Patients with a history of alcohol intolerance or hypersensitivity to Cremor.
(19) Patients with a history of active tuberculosis infection.

Related Information

• Primary Sponsor: Ozaki Yukinori
• Source(s) of Monetary Support: CHUGAI PHARMACEUTICAL CO., LTD.,CHUGAI PHARMACEUTICAL CO., LTD.