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Estrogen Receptor and/or Progesterone Receptor PositivePhase 2NCT03477396

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

A Phase 2 study testing Aromatase Inhibitor, Laboratory Biomarker Analysis and Pharmacokinetic Study in people with Estrogen Receptor and/or Progesterone Receptor Positive and HER2/Neu Negative, run by City of Hope Medical Center at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 70 years and older
What is being tested?
Aromatase Inhibitor, Laboratory Biomarker Analysis and Pharmacokinetic Study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
9 sitesUnited States
Study dates
14 Jun 2018to 5 Jun 2023
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 70 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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
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  • 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)
  • Phosphorous
  • Serum creatinine < 1.5 mg/dL or creatinine clearance >= 50 mL/min, at screening
  • In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN); if the patient has liver metastases, ALT and AST < 5 x ULN, at screening
  • Total bilirubin < ULN; or total bilirubin =< 3.0 x ULN or direct bilirubin =< 1.5 x ULN in patients with well-documented Gilbert's syndrome, at screening
  • Patient with available standard 12-lead electrocardiogram (ECG) with the following parameters at screening (defined as the mean of the triplicate ECGs):
  • Fridericia's corrected QT (QTcF) interval at screening < 450msec (using Fridericia's correction)
  • Resting heart rate 50-90 beats per minute (bpm)

Who cannot join

  • 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
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  • 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
  • Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication
  • Inability to determine the QT interval on screening (QTcF, using Fridericia's correction)
  • Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
  • Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug:
  • Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
  • That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
  • Herbal preparations/medications, dietary supplements
  • Warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), newer anticoagulation agents such as direct factor Xa inhibitors, or fondaparinux is allowed
  • Patient is currently receiving or has received systemic corticosteroids =< 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment
  • The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
  • 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)
  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.)
  • Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer
  • Patient has had major surgery and/or radiotherapy within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery)
  • Patient with a Child-Pugh score B or C
  • Patient has not recovered from the acute effects of prior systemic therapy (until the toxicity resolves to either baseline or at least grade 1) except for residual alopecia or peripheral neuropathy
  • Patient has a history of non-compliance to medical regimen or inability to grant consent
  • Sexually active males unless they use a condom during intercourse while taking the drug and for 21 days after stopping treatment and should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • City of Hope Corona

    Corona, California, 92879

  • City of Hope Medical Center

    Duarte, California, 91010

  • City of Hope Antelope Valley

    Lancaster, California, 93534

  • City of Hope Mission Hills

    Mission Hills, California, 91345

  • City of Hope Rancho Cucamonga

    Rancho Cucamonga, California, 91730

  • Wilmot Cancer Institute

    Rochester, New York, 14642

  • City of Hope South Pasadena

    South Pasadena, California, 91030

  • City of Hope West Covina

    West Covina, California, 91790

Other trials in United States

About this study

Official title: A Phase IIA Trial Assessing the Tolerability of Ribociclib in Combination With an Aromatase Inhibitor in Patients Aged 70 and Older With Hormone Receptor Positive Metastatic Breast Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the safety and tolerability of the combination of ribociclib and an aromatase inhibitor in adults age 70 or older with hormone receptor positive metastatic breast cancer.

SECONDARY OBJECTIVES:

  1. To describe the full toxicity profile including all grades. II. To estimate the rate of worst grades of myelosuppression (neutropenia, leukopenia, thrombocytopenia, and anemia), neutropenic fever, gastrointestinal (GI) side effects (nausea, diarrhea, decreased appetite, vomiting, stomatitis), fatigue, neuropathy, and thromboembolism.

III. To describe rates of dose reductions, dose holds, and hospitalizations. IV. To estimate objective response rate and clinical benefit rate as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) criteria.

  1. To estimate median progression-free and overall survival.

EXPLORATORY OBJECTIVES:

  1. To estimate the rate of adherence to ribociclib. II. To explore factors other than chronologic age that can affect toxicity rates as identified using a cancer-specific geriatric assessment.

III. To describe the results of the Was It Worth It (WIWI) and the results of the Overall Treatment Utility (OTU) Questionnaires.

OUTLINE:

Participants receive ribociclib orally (PO) once daily (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.

After completion of study treatment, participants are followed up at 30 days, then annually thereafter.

Being tested
Aromatase Inhibitor, Laboratory Biomarker Analysis, Pharmacokinetic Study, Questionnaire Administration, Ribociclib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aromatase InhibitorDrug

    Also called Androstenedione Aromatase Inhibitor, Estrogen Synthase Inhibitor, Estrogen Synthetase Inhibitor

    Aromatase inhibitor per treating investigator's discretion

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacokinetic StudyOther

    Also called PHARMACOKINETIC, PK Study

    Correlative studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • RibociclibDrug

    Also called Kisqali, LEE-011, LEE011

    Given PO

Study groups in NCT03477396
Study groupRoleWhat they receive
Treatment (ribociclib, aromatase inhibitor)ExperimentalParticipants 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.
Receives: Drug: Aromatase Inhibitor; Other: Laboratory Biomarker Analysis; Other: Pharmacokinetic Study; Other: Questionnaire Administration; Drug: Ribociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (5)

  1. Number of Participants With Dose Reductions

    Measured: Up to 3.5 years

  2. Number of Participants With Dose Delays

    Measured: Up to 3.5 years

  3. Number of Participants With Dose Discontinuations

    Measured: Up to 3.5 years

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

    Objective response rate (defined as complete response [CR] + partial response [PR]) as determined by RECIST criteria

    Complete Response (CR): Disappearance of all target lesions. Lymph node CR is when the lymph node has decreased to less than 10mm in the short axis.

    Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

    Measured: Up to 3.5 years

  5. Clinical Benefit Rate as Determined by RECIST

    Clinical benefit rate (defined as CR+PR+ stable disease) as determined by RECIST

    Complete Response (CR): Disappearance of all target lesions. Lymph node CR is when the lymph node has decreased to less than 10mm in the short axis.

    Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

    Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

    Measured: Up to 3.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2018
  2. Study start14 Jun 2018
  3. Primary completion29 Sep 2021
  4. Study completion5 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03477396
Sponsor's protocol ID
17471
Other IDs
NCI-2018-00370, 17471
Status last verified
Feb 2024
First submitted
13 Mar 2018
Last updated
20 Feb 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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