Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03477396
Recruitment Status : Active, not recruiting
First Posted : March 26, 2018
Last Update Posted : October 16, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

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.

Condition or disease Intervention/treatment Phase
Estrogen Receptor and/or Progesterone Receptor Positive HER2/Neu Negative Stage IV Breast Cancer AJCC v6 and v7 Drug: Aromatase Inhibitor Other: Laboratory Biomarker Analysis Other: Pharmacokinetic Study Other: Questionnaire Administration Drug: Ribociclib Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.

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

EXPLORATORY OBJECTIVES:

I. 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 14, 2018
Estimated Primary Completion Date : June 14, 2020
Estimated Study Completion Date : June 14, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ribociclib

Arm Intervention/treatment
Experimental: Treatment (ribociclib, aromatase inhibitor)
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
Aromatase inhibitor per treating investigator's discretion
Other Names:
  • Androstenedione Aromatase Inhibitor
  • Estrogen Synthase Inhibitor
  • Estrogen Synthetase Inhibitor

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacokinetic Study
Correlative studies
Other Names:
  • PHARMACOKINETIC
  • PK Study

Other: Questionnaire Administration
Ancillary studies

Drug: Ribociclib
Given PO
Other Names:
  • Kisqali
  • LEE-011
  • LEE011




Primary Outcome Measures :
  1. Incidence of grade 2 and above toxicities attributed (possible or above) to ribociclib [ Time Frame: Up to 30 days of last study drug ]
    Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.


Secondary Outcome Measures :
  1. Incidence of adverse events associated with the combinations as measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ]
    Tables will be created to summarize the toxicities and side effects by age strata, course, organ, severity and attribution for all patients.

  2. Dose reductions [ Time Frame: Up to 2 years ]
    Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

  3. Dose delays [ Time Frame: Up to 2 years ]
    Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

  4. Dose discontinuations [ Time Frame: Up to 2 years ]
    Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

  5. Objective response rate (defined as complete response [CR] + partial response [PR]) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: Up to 2 years ]
    Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

  6. Clinical benefit rate (defined as CR+PR+ stable disease) as determined by RECIST [ Time Frame: Up to 2 years ]
    Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

  7. Progression free survival defined as the time from start of treatment to the first of the following disease events: local/regional/distant recurrence, invasive contralateral breast disease, second primary or death due to any cause [ Time Frame: From start of treatment up to 2 years ]
    Will be estimated using the product limit method of Kaplan and Meier/ Cox proportional hazards methods.

  8. Overall survival defined as the time from start of treatment to death due to any cause [ Time Frame: From start of treatment up to 2 years ]
    Will be estimated using the product limit method of Kaplan and Meier/ Cox proportional hazards methods.

  9. Average plasma steady-state ribociclib C trough concentrations in patients over the age of 70 years [ Time Frame: Up to 2 years ]
    The relationship between plasma trough and percent drop in neutrophil counts using linear models.

  10. Average plasma steady-state ribociclib C trough concentrations in patients over the age of 70 years [ Time Frame: Up to 2 years ]
    The relationship between plasma trough and percent drop in platelet counts using linear models.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
    • 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)

Exclusion Criteria:

  • 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
      • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03477396


Locations
Layout table for location information
United States, California
City of Hope Corona
Corona, California, United States, 92879
City of Hope Medical Center
Duarte, California, United States, 91010
City of Hope Antelope Valley
Lancaster, California, United States, 93534
City of Hope Mission Hills
Mission Hills, California, United States, 91345
City of Hope Rancho Cucamonga
Rancho Cucamonga, California, United States, 91730
City of Hope South Pasadena
South Pasadena, California, United States, 91030
City of Hope West Covina
West Covina, California, United States, 91790
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Wilmot Cancer Institute
Rochester, New York, United States, 14642
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Mina Sedrak, MD City of Hope Medical Center

Layout table for additonal information
Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT03477396     History of Changes
Other Study ID Numbers: 17471
NCI-2018-00370 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17471 ( Other Identifier: City of Hope Medical Center )
First Posted: March 26, 2018    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Estrogens
Aromatase Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists