Fulvestrant or Exemestane with or without Ribociclib in Patients with Recurrent, Unresectable, or Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer

Active:	No
Cancer Type:	Breast Cancer	NCT ID:	NCT02632045
Trial Phases:	Phase II	Protocol IDs:	AAAP9506 (primary) NCI-2016-01092 s15-01200
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT02632045

Summary

This randomized, phase II trial studies how well fulvestrant or exemestane with or without ribociclib works in treating patients with hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer that has progressed after treatment with an aromatase inhibitor or cyclin-dependent kinase 4/6 inhibitor (recurrent), cannot be removed by surgery (unresectable), or has spread to other parts of the body (metastatic). Hormone therapy using fulvestrant or exemestane may fight breast cancer by blocking the use of estrogen by the tumor cells or reducing the amount of estrogen made by the body. Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving fulvestrant or exemestane with ribociclib may be an effective treatment for patients with breast cancer.

Objectives

PRIMARY OBJECTIVE:
I. To evaluate the progression-free survival (PFS) of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibitor in patients with hormone receptor positive (HR+), HER2- breast cancer.

SECONDARY OBJECTIVES:
I. To assess the overall response rate (ORR = complete + partial response rate) and clinical benefit rate (CBR= ORR + stable disease rate at >= 24 weeks of follow up) in the study population in both arms of the trial, post-randomization.
II. To assess the PFS, ORR, CBR, and safety of ribociclib with an aromatase inhibitor in patients with metastatic or unresectable HR+ HER2- breast cancer.
III. To explore differences in clinical outcome (PFS, ORR, CBR) in patients receiving an aromatase inhibitor plus ribociclib versus (vs.) palbociclib vs. abemaciclib (scenario 1), both prior to randomization and then after continuation of CDK4/6 inhibition.
IV. To evaluate the rates of adverse events and tolerability of the combination of fulvestrant or exemestane with and without ribociclib.
V. To explore potential predictive tumor and blood-based predictive biomarkers.
VI. To assess the impact of the combination therapy vs. fulvestrant or exemestane alone on patient reported global health assessment and quality of life.

OUTLINE: Patients are assigned to Scenario 1 or Scenario 2.

Scenario 1: Patients receive ribociclib orally (PO) once daily (QD) on days 1-21 and letrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression are then assigned to Scenario 2.

Scenario 2: Patients are randomized to 1 of 2 arms.

Arm A: Patients receive ribociclib PO QD on days 1-21. Patients also receive fulvestrant intramuscularly (IM) every 2 weeks for 6 weeks then every 4 weeks or exemestane PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Arm B: Patients receive placebo PO QD on days 1-21 and fulvestrant IM or exemestane PO as in Arm A. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 12 weeks thereafter.

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