Ribociclib and Aromatase Inhibitor in Treating Older Participants With Hormone Receptor Positive Metastatic Breast Cancer

NCT03477396 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17471NCI-2018-00370
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 9

Brief Summary

This phase IIA trial studies the side effects of ribociclib and aromatase inhibitor and how well they work in treating participants with hormone receptor positive breast cancer that has spread to other places in the body. Ribociclib and aromatase inhibitors may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IV Breast Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Grade 2 and Above Toxicities Attributed to Ribociclib

  Number of participants with grade 2 and above toxicities attributed (possible, probable or definite) to ribociclib

  Up to 30 days of last study drug, about 3 years and 3 months

Secondary Outcomes (5)

• Number of Participants With Dose Reductions

  Up to 3.5 years

• Number of Participants With Dose Delays

  Up to 3.5 years

• Number of Participants With Dose Discontinuations

  Up to 3.5 years

• Objective Response Rate by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

  Up to 3.5 years

• Clinical Benefit Rate as Determined by RECIST

  Up to 3.5 years

Study Arms (1)

Treatment (ribociclib, aromatase inhibitor)

EXPERIMENTAL

Participants receive ribociclib orally PO QD on days 1-21 and aromatase inhibitor per treating investigator's discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Aromatase Inhibitor; Other: Laboratory Biomarker Analysis; Other: Pharmacokinetic Study; Other: Questionnaire Administration; Drug: Ribociclib

Interventions

Aromatase Inhibitor DRUG

Aromatase inhibitor per treating investigator's discretion

Also known as: Androstenedione Aromatase Inhibitor, Estrogen Synthase Inhibitor, Estrogen Synthetase Inhibitor

Treatment (ribociclib, aromatase inhibitor)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ribociclib, aromatase inhibitor)

Pharmacokinetic Study OTHER

Correlative studies

Also known as: PHARMACOKINETIC, PK Study

Treatment (ribociclib, aromatase inhibitor)

Questionnaire Administration OTHER

Ancillary studies

Treatment (ribociclib, aromatase inhibitor)

Ribociclib DRUG

Given PO

Also known as: Kisqali, LEE-011, LEE011

Treatment (ribociclib, aromatase inhibitor)

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patient has signed the informed consent (ICF) prior to any study procedures being performed and is able to comply with protocol requirements
• Must be able to swallow ribociclib
• Age: \>= 70 years at time of enrollment \>= 70 to \< 74 years, \>= 75 years
• \* NOTE: A minimum of 20 participants must be \>= 75 years. The remaining 20 participants may be \>= 70 to \< 74 years OR \>= 75 years
• Subjects must be able to communicate with the investigator and comply with the requirements of the study procedures
• Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer, HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+, and metastatic breast cancer
• First or second line endocrine therapy for metastatic disease. One prior line of chemotherapy for metastatic disease is allowed
• Absolute neutrophil count \>= 1.5 x 10\^9 /L, at screening
• Platelets \>= 100 x 10\^9 /L, at screening
• Hemoglobin \>= 9.0 g/dL, at screening
• Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplement before the first dose of study medication:
• Sodium
• Potassium
• Magnesium
• Total calcium (corrected for serum albumin)

You may not qualify if:

• Patient received prior treatment with any CDK4/6 inhibitor
• Patient has a known hypersensitivity to any of the excipients of ribociclib
• Patients with a prior malignancy diagnosed within 2 years AND with evidence of disease (except adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer)
• Patient with concurrent malignancy that is not clinically stable AND needs tumor-directed therapy
• Patients with central nervous system (CNS) involvement unless they meet ALL the following criteria:
• Untreated brain metastases (e.g., lesions \< 1cm) not needing immediate local therapy
• Previously treated brain metastases not needing immediate local therapy
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
• Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
• Documented cardiomyopathy
• Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block).
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (9)

City of Hope Corona

Corona, California, 92879, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope Antelope Valley

Lancaster, California, 93534, United States

Location

City of Hope Mission Hills

Mission Hills, California, 91345, United States

Location

City of Hope Rancho Cucamonga

Rancho Cucamonga, California, 91730, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

City of Hope West Covina

West Covina, California, 91790, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Wilmot Cancer Institute

Rochester, New York, 14642, United States

Location

MeSH Terms

Interventions

Aromatase Inhibitors; Pharmacogenomic Variants; ribociclib

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Polymorphism, Genetic; Genetic Variation; Genetic Phenomena

Results Point of Contact

• Title: Dr. MIna Sedrak
• Organization: City of Hope

msedrak@coh.org

626-359-8111

Study Officials

• Mina Sedrak, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2018
• First Posted: March 26, 2018
• Study Start: June 14, 2018
• Primary Completion: September 29, 2021
• Study Completion: June 5, 2023
• Last Updated: February 20, 2024
• Results First Posted: May 18, 2022

Record last verified: 2024-02

Locations

US (9)