Clinical trial NCT03078751: Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- High Risk Early Breast Cancer
Official title: An Open Label, Multi-center Protocol for U.S. Patients Enrolled in a Study of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative, High Risk Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Hormone receptor-positive
Estrogen and/or progesterone receptor-positive
HER2-negative
High risk early breast cancer
Adjuvant
Ribociclib
LEE011
CDK4/6 inhibitor
Endocrine therapy
Phase II
Breast carcinoma
Breast cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-03-13
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was an open label, multi-center protocol for U.S. patients enrolled in the study of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, high risk early breast cancer

Detailed description: The purpose of this study was to evaluate the preliminary safety and tolerability of ribociclib to standard adjuvant endocrine therapy (ET) in patients with hormone receptor (HR) positive, Human Epidermal Growth Factor Receptor2 (HER2) negative high risk early breast cancer (EBC).

Originally, this was a randomized, Phase III, double-blind, placebo-controlled, multi-center, international study to evaluate efficacy and safety of ribociclib with ET as an adjuvant treatment in patients with HR-positive, HER2-negative, high risk EBC.

Patients were randomized at a ratio of 1:1 to receive either ribociclib or placebo for approximately 24 months in combination with a standard adjuvant ET with ET continued for at least 60 months.

However, following a review of the ribociclib development program strategy, a decision was taken to explore a different approach by initiating a single Phase III study for simplicity of trial logistics and for the purpose of analyzing the overall population through a single clinical trial. Therefore, this study was closed to enrollment early and was amended to be an open label, multi-center Phase II study conducted in the US only. All randomized patients were unblinded; patients randomized to placebo were permanently discontinued from the study and patients randomized to ribociclib were offered the option to continue treatment with ribociclib + ET.

The study included a screening phase (28 days), a treatment phase composed of maximum of 26 cycles of ribociclib in combination with ET (approximately 24 months) or until disease recurrence, intolerable toxicity, withdrawal of consent, or discontinuation from the study treatment for any other reason, whichever was earlier, and a 30 days safety follow up from last dose of ribociclib. Ribociclib was given orally once a day on days 1 to 21 in each 28 days cycle.

Safety was assessed for each patient until 30 days after the last dose of ribociclib and included routine safety monitoring except in case of death, loss to follow up or withdrawal of consent.

Eligibility criteria: Key Inclusion Criteria:

* Histologically confirmed unilateral primary invasive adenocarcinoma of the breast
* Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast cancer
* Patient is after surgical resection of the tumor where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor and with available archival tumor tissue from the surgical specimen
* Patient who received adjuvant chemotherapy and have AJCC 8th edition Prognostic Stage Group III tumor; or patient who received neoadjuvant chemotherapy and have 1 or more ipsilateral axillary lymph nodes with residual tumor metastases greater than 2.0 mm in lymph node(-s) and residual tumor greater than 10.0 mm in breast tissue
* Patient has completed multi-agent adjuvant or neoadjuvant chemotherapy of ≥ 4 cycles or ≥ 12 weeks which included taxanes prior to screening
* Patient has completed adjuvant radiotherapy (if indicated) prior to screening
* Patient may already have initiated adjuvant endocrine therapy (ET) at the time of randomization, but randomization must take place within 52 weeks of date of initial histological diagnosis of breast cancer and within 12 weeks of initiating ET
* ECOG Performance Status 0 or 1
* Adequate bone marrow and organ function
* Sodium, potassium, phosphorus, magnesium and total calcium laboratory values within normal limits
* QTcF interval \< 450 msec and mean resting heart rate 50-90 bpm

Key Exclusion Criteria:

* Prior treatment with CDK4/6 inhibitor
* Prior treatment with tamoxifen, raloxifen or aromatase inhibitors for reduction in risk (chemoprevention) of breast cancer and/or treatment for osteoporosis within last 2 years
* Prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin or 900 mg/m² or more for epirubicin
* Distant metastases of breast cancer beyond regional lymph nodes
* Patient has not recovered from clinical and laboratory acute toxicities of chemotherapy, radiotherapy and surgery
* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, or clinically significant cardiac arrhythmias
* Uncontrolled hypertension with systolic blood pressure \>160 mmHg
* Patient is currently receiving any of the prohibited substances that cannot be discontinued 7 days prior to Cycle 1 Day 1: concomitant medications, herbal supplements, and/or fruits and their juices that are known as strong inhibitors or inducers of CYP3A4/5; medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5; systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment; concomitant medications with a known risk to prolong the QT interval and/or known to cause torsades de points that cannot be discontinued or replaced by safe alternative medication.
* Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the study
* Women of child-bearing potential unless they are using highly effective methods of contraception during the study treatment and for 21 days after stopping the study treatment.

Primary outcomes:
measure: Number of Participants With Adverse Events and Serious Adverse Events
timeFrame: Up to 26 months
measure: Percentage of Participants With Adverse Events and Serious Adverse Events
timeFrame: Up to 26 months
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates PC- HAL
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Bakersfield
country: United States
facility: CBCC Global Research
state: California
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology and Oncology
state: California
city: Redondo Beach
country: United States
facility: TRIO - Torrance Health Association
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers Regulatory
state: Colorado
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists South Region
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North Florida Cancer Specialist N
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital Central Research Dept.
state: Georgia
city: Savannah
country: United States
facility: Summit Cancer Care, PC
state: Georgia
city: Leawood
country: United States
facility: Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Div.
state: Kansas
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology P A
state: Maryland
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Livingston
country: United States
facility: Saint Barnabas Medical Center 2nd Floor East Wing
state: New Jersey
city: New Hyde Park
country: United States
facility: Pro Health Care Associates
state: New York
city: Charlotte
country: United States
facility: The Presbyterian Hospital
state: North Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology P A Texas Oncology - Houston
state: Texas
city: Houston
country: United States
facility: Millennium Oncology
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Network of South Texas
state: Texas
city: Tyler
country: United States
facility: Texas Oncology PA - Tyler
state: Texas
city: Fairfax
country: United States
facility: Fairfax Northern Virginia Hem/Onc
state: Virginia
city: Tacoma
country: United States
facility: Multicare Institute for Research and Innovation
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital and Clinics
state: Washington
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, Sparano JA, Hunsberger S, Enos RA, Gelber RD, Zujewski JA. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007 May 20;25(15):2127-32. doi: 10.1200/JCO.2006.10.3523.
citation: Hortobagyi GN, Connolly JL, D'Orsi CJ, et al (2017). Breast. From AJCC Cancer Staging Manual 8th ed. By Amin MB, Edge S, Greene FL, et al. Springer