CDK 4/6 Inhibitor, Ribociclib, With Adjuvant Endocrine Therapy for ER-positive Breast Cancer

NCT03285412 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 17-232
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is studying a drug as a possible treatment for ER-positive Breast Cancer The drug involved in this study is:

• Ribociclib

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• ctDNA clearance

  tumor ctDNA response after 12 cycles of adjuvant ribociclib in combination with endocrine therapy vs endocrine therapy alone in patients with localized post-menopausal breast cancer and elevated ctDNA.

  12 Months

Secondary Outcomes (3)

• Comparison of Adverse Events

  2 years

• Number of participants who have a switch in endocrine therapy

  2 years

• Disease-free survival (DFS)

  2 years

Study Arms (2)

Ribociclib + Endocrine Rx

EXPERIMENTAL

Ribociclib will be administered. Endocrine therapy will be administered.

Drug: Ribociclib; Other: Endocrine therapy

Endocrine Rx

ACTIVE COMPARATOR

Endocrine therapy will be administered.

Other: Endocrine therapy

Interventions

Ribociclib DRUG

Ribociclib is a drug designed to block certain proteins called cyclin-dependent protein kinases 4 and 6 (CDK4/6). These proteins are needed for cells to divide and may also control the ability of certain cancers to grow.

Also known as: Kisqali

Ribociclib + Endocrine Rx

Endocrine therapy OTHER

Hormone therapy

Endocrine Rx; Ribociclib + Endocrine Rx

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have biopsy proven localized ER+ (≥ 10%), HER2 negative, invasive breast cancer, with pathological stage (including post-neoadjuvant therapy) T1c-T4c, any N, M0, by AJCC 7th edition staging. Invasive breast cancer must be ER+ in ≥10% of the cells and HER2 negative (IHC 0 or 1+ and/or FISH negative with a ratio \<2) by ASCO/CAP guidelines. For IHC 2+, the tumor must be FISH negative with a ratio \<2. PR status must be performed. ER, PR and HER2 measurements should be performed according to institutional (local) guidelines, in a CLIA-approved setting. Evaluation for metastatic disease is not required in the absence of symptoms. Patients must have completed definitive surgery for breast cancer.
• Detectable ctDNA
• No prior history of other malignancies within past 5 year (besides breast cancer as per 3.1.1). Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. No concurrent malignancy or other serious medical condition as deemed by the investigator.
• Participants may or may not have received (neo)adjuvant chemotherapy, but must be at least 4 weeks after last dose of chemotherapy and/or biological therapy at the time of screening, with no more than grade 1 residual toxicity (except ≤ grade 2 neuropathy or ≤ grade 2 alopecia).
• Participants may or may not have received adjuvant radiotherapy, but must be at least 30 days after last dose radiotherapy, with no more than grade 1 residual toxicity at the time of screening.
• Pre- and postmenopausal women are eligible. Premenopausal women must have a negative serum or urine pregnancy test. Pregnancy testing does not need to be pursued in female patients who are: age ≥ 60 years; or age \< 60 with intact uterus and amenorrhea for 12 consecutive months or more AND estrogen (estradiol) levels within postmenopausal range; or status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation.
• QTc (Fredericia's formula) \< 470ms.
• Must be ≥ 18 years of age.
• Prior CDK 4/6 inhibitor is permitted provided it was more than 12 months ago (from consent date).
• ECOG performance status 0-1 (Karnofsky ≥70%, see Appendix A)
• Patients may enroll within 20 years of breast cancer diagnosis, as long as there is a plan for at least 1 more year of adjuvant endocrine therapy.
• Ability to understand and the willingness to sign a written informed consent document. Patient must sign the Informed Consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements.
• Currently on adjuvant endocrine therapy (tamoxifen and/or aromatase inhibitor (AI)), i.e prior use of any AI, including letrozole, anastrozole or exemestane, or tamoxifen is allowed. However, tamoxifen use is not allowed during the study with ribociclib. Patients on tamoxifen interested in this trial could be switched to AI on C1D1 or before/during screening. Concurrent GNRH agonist is allowed, and is recommended with AI in pre/peri-menopausal patients.
• Patient has adequate bone marrow and organ function as defined by the following laboratory values at screening:
• Absolute neutrophil count ≥1.5 × 109/L

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participants who are receiving any other investigational agents.
• Participants with known brain metastases, or any other metastases from cancer.
• Participants receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including any of the following:
• History of angina pectoris, symptomatic pericarditis, coronary artery bypass graft (CABG) or myocardial infarction within 6 months prior to study entry.
• Documented cardiomyopathy.
• Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) detected during screening.
• History of cardiac failure, significant/symptomatic bradycardia, Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following:
• Known risk to prolong the QT interval or induce Torsade's de Pointes.
• Uncorrected hypomagnesemia or hypokalemia.
• Systolic Blood Pressure (SBP) \>160 mmHg or \<90 mmHg.
• Bradycardia (heart rate \<50 at rest), by ECG or pulse.
• On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF \>450 screening ECG (based on a mean of 3 ECGs).

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Novartis: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mass General/North Shore Cancer Center

Danvers, Massachusetts, 01923, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Arielle Medford, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 18, 2017
• Study Start: December 12, 2017
• Primary Completion: April 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)