A phase II double-arm study of the switch of Endocrine therapy with the continuation of CDK4/6 inhibitor vs. switch of endocrine therapy alone as second-line and beyond in ER-positive breast cancer patients ( SECURE study).

Treatment studies /Interventional Studies : Randomized Controlled Trial Open Labeled

Study Design Type of study

Double-arm prospective phase II open-label. Patient number - 64 patients in each arm Time schedule - Recruitment will commence post institutional review board (IRB) clearance of the proposed study. The study will start in TMH once approval is obtained from the IRB.

Recruitment in other centers will start after individual institution clearance for the study is obtained. Approximate accrual time - 36 months. Approximate time for follow-up - 6 months post accrual of last patients. Final study report – approximately 42 months post the beginning of the study. Number of centres - 1

Primary Endpoints :

To evaluate Progression-free survival (PFS) at 6 months of endocrine therapy with the continuation of CDK4/6 inhibitors vs. endocrine therapy alone as second-line and beyond therapy in advanced metastatic breast cancer.

Secondary Endpoints :

To evaluate Overall Survival (OS) of endocrine therapy with the continuation of CDK4/6 inhibitors vs. endocrine therapy alone as second-line and beyond therapy in advanced metastatic breast cancer.

To evaluate the tolerability of endocrine therapy with the continuation of CDK4/6 inhibitors vs. endocrine therapy alone as second-line and beyond therapy in advanced metastatic breast cancer.

To evaluate Progression-free survival (PFS) at 3 and 12 months of endocrine therapy with the continuation of CDK4/6 inhibitors vs. endocrine therapy alone as second-line and beyond therapy in advanced metastatic breast cancer.

To evaluate the Quality of life (QOL) of endocrine therapy with the continuation of CDK4/6 inhibitors vs. endocrine therapy alone as second-line and beyond therapy in advanced metastatic breast cancer.

Eligibility

Inclusion Criteria :

a. Women of age 18 years or older with locally advanced, unresectable, or metastatic breast cancer.

b. ECOG 0 - 2 and adequate bone marrow, hepatic, and renal function and willing to give informed consent. Patients could have either measurable or non-measurable diseases defined by RECIST version 1.1.

c. Tumors that are positive for the ER and/or progesterone receptor are defined as > 1%. Human epidermal growth factor receptor 2 (HER2) status should be negative.

d. Patients may have received (neo)adjuvant chemotherapy ( > 12 months since completion of chemotherapy) and any duration of adjuvant ET (< 4 weeks of ET for MBC before trial registration).

Exclusion Criteria :

a. Patients with more than 1 prior therapy for MBC. Known brain or leptomeningeal metastasis or life expectancy < 12 weeks or serious or uncontrolled concurrent medical illness

b. History of second primary malignancies.

Study methodology:

Participants fulfilling all in-/exclusion criteria, and having provided written informed consent on the approved informed consent form are eligible for participation in the study. They would then be enrolled in the study.

Further, the enrolled Participants will be randomized into a 1:1 ratio into arms Arm A standard treatment + continuation of CDK4/6 inhibitor Arm B standard treatment alone Post-randomization participants will receive the treatment as detailed below. Treatment Patients will be randomized to either Arm A or Arm B

ARM A Fulvestrant/Letrozole/exemestane + Ribociclib/ Palbociclib/ Abemaciclib.

Ribociclib will be administered at 600 mg PO for 21 consecutive days with 7 days back. Palbociclib will be given at 125 mg PO dose for 21 consecutive days with 7 days gap. Abemaciclib will be given at 150 mg PO BD dose continuously.

ARM B Fulvestrant/Letrozole/exemestane alone