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Study of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer (PMR)

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ClinicalTrials.gov Identifier: NCT03822468
Recruitment Status : Recruiting
First Posted : January 30, 2019
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

QT interval prolongation and neutropenia are considered to be important identified risks for ribociclib (Kisqali® Prescribing Information, Investigator Brochure). The approved dosing regimen of ribociclib is 600 mg daily (QD) on a 3 weeks on/1 week off schedule.

The purpose of the study is to explore whether a reduced dosing regimen of 400 mg ribociclib orally QD 3 weeks on/1 week off may decrease the risk of QTc prolongation without compromising the efficacy of ribociclib in combination with an NSAI in pre- and postmenopausal women with HR-positive, HER2-negative aBC who have received no prior therapy for advanced disease. The risks of other AEs of special interest, such as neutropenia and hepatobiliary toxicity will be evaluated in this study as well.

Approximately 350 patients will be randomly assigned to one of the below treatment arms in a 1:1 ratio: Experimental arm (Arm 1) - Ribociclib 400 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Control arm (Arm 2) - Ribociclib 600 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Randomization will be stratified by the presence of lung and/or liver metastases (yes versus no).


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Ribociclib Drug: Letrozole or Anastrozole Drug: Goserelin Phase 2

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Study Type : Interventional
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Randomized, Open-label Study to Evaluate the Safety and Efficacy of 400 mg of Ribociclib in Combination With Non-steroidal Aromatase Inhibitors for the Treatment of Pre- and Postmenopausal Women With Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease
Actual Study Start Date : June 11, 2019
Estimated Primary Completion Date : February 2, 2026
Estimated Study Completion Date : February 2, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Ribociclib 400 mg
Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
Drug: Ribociclib
Ribociclib will be supplied as 200 mg tablets as individual patient supply packaged bottles taken by mouth.
Other Name: LEE011

Drug: Letrozole or Anastrozole
Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously (investigator choice)

Drug: Goserelin
Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

Active Comparator: Ribociclib 600 mg
Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
Drug: Ribociclib
Ribociclib will be supplied as 200 mg tablets as individual patient supply packaged bottles taken by mouth.
Other Name: LEE011

Drug: Letrozole or Anastrozole
Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously (investigator choice)

Drug: Goserelin
Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: At least 6 months ]
    ORR is based on local tumor assessments (RECIST version 1.1) for all patients that have been treated for at least 6 months or have discontinued the study treatment.


Secondary Outcome Measures :
  1. Δ QTcF at Cycle 1 Day 15 (at 2h post-dose) (Key Secondary Endpoint) [ Time Frame: Cycle 1 Day 15 (2 hours post dose) ]
    To evaluate QTc (with Fridericia's correction) prolongation in the experimental arm

  2. Progression-free survival (PFS) [ Time Frame: Approximately 36 months ]
    PFS per RECIST 1.1

  3. Clinical benefit rate (CBR) [ Time Frame: Approximately 36 months ]
    CBR per RECIST 1.1

  4. Time to response (TTR) [ Time Frame: Approximately 36 months ]
    TTR per RECIST 1.1

  5. Duration of response (DOR) [ Time Frame: Approximately 36 months ]
    DOR per RECIST 1.1

  6. Pharmacokinetics (PK) of ribociclib: Cmax [ Time Frame: Cycle 1 Day 15 ]
    when given in combination with NSAI

  7. Pharmacokinetics (PK) of ribociclib: Tmax [ Time Frame: Cycle 1 Day 15 ]
    when given in combination with NSAI

  8. Pharmacokinetics (PK) of ribociclib: AUC0 - 24h [ Time Frame: Cycle 1 Day 15 ]
    when given in combination with NSAI



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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion criteria:

Patient has advanced (loco-regionally recurrent or metastatic) breast cancer not amenable to curative therapy.

Patient has a histologically and/or cytologically confirmed diagnosis of ER-positive and/or PgR-positive breast cancer based on the most recently analyzed tissue sample, and all tested by local laboratory.

Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample.

Patient must have measurable disease, i.e., at least one measurable lesion according to RECIST version 1.1. (a lesion in a previously irradiated site may only be counted as a target lesion if there is clear evidence of progression since the irradiation).

Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central laboratory:

  • QTc interval at screening < 450 ms (using Fridericia's correction)
  • Mean resting heart rate 50 to 90 bpm (determined from the ECG)

Women of childbearing potential (CBP), defined as all women physiologically capable of becoming pregnant, must have confirmed negative serum pregnancy test (for β-hCG) within 14 days prior to randomization.

Women of CBP must be willing to use highly effective methods of contraception.

Key Exclusion Criteria:

Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's judgment.

Patient who received any prior systemic anti-cancer therapy(including endocrine therapy, chemotherapy, prior CDK4/6 inhibitors) for aBC. Patients who received neo-/adjuvant therapy for breast cancer are eligible.

Patient is concurrently using other anti-cancer therapy.

Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major toxicities.

Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization, and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).

Patient has a concurrent malignancy or malignancy within 3 years of the randomization date, with the exception of adequately treated basal or squamous cell skin carcinoma, or curatively resected cervical carcinoma in situ.

Patients with central nervous system (CNS) involvement unless they meet specific stability criteria.

Patient has clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.

Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, and has not fully recovered from side effects of such treatment.

Other protocol-defined Inclusion/Exclusion may apply.


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): NCT03822468


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03822468     History of Changes
Other Study ID Numbers: CLEE011A2207
2018-004234-15 ( EudraCT Number )
First Posted: January 30, 2019    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Breast Cancer
HR-positive
HER2-negative
ER-positive
advanced breast cancer
ribociclib
LEE011
premenopausal
postmenopausal
Additional relevant MeSH terms:
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Breast Neoplasms
Breast Diseases
Neoplasms by Site
Neoplasms
Skin Diseases
Letrozole
Anastrozole
Goserelin
Aromatase Inhibitors
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal