Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in taken along with Letrozole for the Treatment of Men and Pre or Postmenopausal Women With HR positive HER2- advanced breast cancer

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/08/009311
• Date of registration: 09-08-2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Healthcare Pvt Ltd
• Public title: Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in taken along with Letrozole for the Treatment of Men and Pre or Postmenopausal Women With HR positive HER2- advanced breast cancer
• Scientific title: An Open-label, Multicenter, Phase IIIb Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre or Postmenopausal Women With Hormone Receptor-positive (HR positive) HER2-negative (HER2-) Advanced Breast Cancer (aBC) With no Prior Hormonal Therapy for Advanced Disease
• Date of first enrolment: 20-09-2017
• Target sample size: 3000
• Recruitment status: Closed to Recruitment of Participants
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=18172
• Study type: Interventional
• Study design: Other; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Open Label
• Phase: Phase 3

Countries of recruitment

Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Costa Rica, Czech Republic, Denmark, Egypt, Finland, France, Greece, Hong Kong, Hungary, India, Israel, Italy, Jordan, Lebanon, Luxembourg, Malaysia, Mexico, Netherlands, Norway, Oman, Panama, Philippines, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Singapore, Slovakia, Slovenia, Spain, Sweden, Taiwan, Thailand, United Arab Emirates, United Kingdom, United States of America

Contacts

• Name: Dr Manish Mistry
• Affiliation: Novartis India Limited

• Name: Dr Manish Mistry
• Affiliation: Novartis India Limited

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patient is an adult, male or female >= 18 years old at the time of informed

consent

2. Male or female advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.

3. In the case of women, both pre or perimenopausal and postmenopausal patients are allowed to be included in this study; menopausal status is relevant for the requirement of goserelin to be used concomitantly with ribociclib and letrozole.

a. Postmenopausal status is defined either by:

I). Prior bilateral oophorectomy OR ii). Age more than or equal to 60 OR iii). Age less than 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range. If patient is taking tamoxifen or toremifene and age less than 60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range.

Note: For women with therapy-induced amenorrhea, serial measurements of FSH and or estradiol are needed to ensure menopausal status.

b. Premenopausal status is defined as either:

I). Patient had last menstrual period within the last 12 months, OR ii). If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, OR iii). In case of therapy induced amenorrhea, plasma estradiol and or FSH must be in the premenopausal range per local normal range.

c. Perimenopausal status is define as neither premenopausal nor postmenopausal Note: Throughout this document, perimenopausal and premenopausal status is grouped together and referred as Premenopausal

4. Patient has a histologically and or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.

5. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1plus or 2plus. If IHC is 2plus, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.

6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status more than or equal to 2

7. Patient has adequate bone marrow and organ function as defined by ALL of the following laboratory values (as assessed by local laboratory):

a. Absolute neutrophil count more than or equal to 1.5 Ã? 10 raised to 9 per L

b. Platelets more than or equal to 100 Ã? 10 raised to 9 per L

c. Hemoglobin more than or equal to 9.0 g per dL

Potassium, sodium, calcium corrected for serum albumin and magnesium within normal limits or corrected to within normal limits with supplements before first dose of the study medication

d. INR less than or equal to 1.5

e. Serum creatinine less than or equal to 1.5 mg per dl or creatinine clearance more than or equal to 50 mL per min

f. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 Ã? ULN. If the patient has liver metastases, ALT and AST should be less than 5 Ã? ULN.

g. Total serum bilirubin less than ULN; or total bilirubin less than or equal to 3.0 Ã? ULN with direct bilirubin within normal range in patients with well documented Gilberts Syndrome

8. Patient must have a 12-lead ECG with ALL of the following parameters at screening:
Exclusion criteria: 1. Patient has a known hypersensitivity to any of the excipients of ribociclib or letrozole

2. Patient who received any CDK4 6 inhibitor

3. Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of metastatic disease is permitted

4. Patient is concurrently using other anti cancer therapy.

5. Patient has had major surgery within 14 days prior to starting study drug or

has not recovered from major side effects.

6. Patient who has not had resolution of all acute toxic effects of prior anti cancer

therapy to NCI CTCAE version 4.03 Grade less than or equal to 1 (except alopecia or other

toxicities not considered a safety risk for the patient at investigators discretion).

7. Patient who has received radiotherapy less than or equal to 4 weeks or limited field radiation for palliation less than or equal to 2 weeks prior to start of treatment, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception

of alopecia) and or from whom more than or equal to 25 percent (Ellis R E 1961) of the bone marrow

was irradiated.

8. Patient has a concurrent malignancy or malignancy within 3 years prior to

starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer

9. Patient with central nervous system metastases unless they meet all of the following criteria

At least 4 weeks from prior therapy for CNS disease completion including

radiation and or surgery to starting the study treatment.

Clinically stable CNS lesions at the time of study treatment initiation and not receiving steroids and or enzyme inducing anti epileptic medications for the management of brain metastases for at least 2 weeks.

10. 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)

11. Patient has a known history of HIV infection (testing not mandatory)

12. Patient has any other concurrent severe and or uncontrolled medical condition

that would, in the investigators 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.)

13. Clinically significant, uncontrolled heart disease and/or cardiac repolarization

abnormalities, including any of the following:

a. 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

b. History of documented congestive heart failure (New York Heart

Association functional classification III-IV)

Documented cardiomyopathy

c. 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

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Men and Pre/Postmenopausal Women With HR positive HER2- advanced Breast Cancer

Intervention(s)

Intervention1: Ribociclib (LEE011): Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg ribociclib QD plus 2.5 mg letrozole QD
Control Intervention1: Letrozole: Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg ribociclib QD + 2.5 mg letrozole QD
Control Intervention2: Goserelin: Only for men and premenopausal women: administered as an injectable subcutaneous implant on Day 1 of each 28 days cycle

Primary Outcome(s)

The number of participants with adverse events as a measure of safety and tolerabilityTimepoint: Up to approximately 36 months

Secondary Outcome(s)

Time-to-Progression (TTP)Timepoint: Up to approximately 36 months

Clinical Benefit Rate (CBR)Timepoint: Up to approximately 36 months

Overall response rate (ORR) for patients with measurable diseaseTimepoint: Up to approximately 36 months

Patient Reported Outcome (PRO) using scores from FACT-B questionaireTimepoint: Up to approximately 36 months

Secondary ID(s)

CLEE011A2404-Protocol Version 01 dated 19-Dec-16

NCT02941926

Source(s) of Monetary Support

Novartis Healthcare Pvt Ltd GDO Trial Monitoring, India 6 & 7 floor , Inspire BKC G Block, BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai Mumbai MAHARASHTRA 400051 India

Ethics review

Status: Approved
Approval date: 28/06/2017
Contact:

Institutional Ethics Committee

Status: Approved
Approval date: 05/07/2017
Contact:

Institutional Review Board-CMC

Status: Approved
Approval date: 10/08/2017
Contact:

HCG Multispeciality Ethics Commttee

Status: Approved
Approval date: 16/08/2017
Contact:

Institutional Review Board-RGCI

Status: Approved
Approval date: 01/09/2017
Contact:

Institutional Ethics Committee-Nobel Hospital

Status: Approved
Approval date: 04/09/2017
Contact:

HCG Triesta institutional ethics commitee

Status: Approved
Approval date: 04/09/2017
Contact:

Institutional Ethics Committee-Indo American

Status: Approved
Approval date: 21/09/2017
Contact:

Institutional Review Board-TMC

Status: Approved
Approval date: 01/11/2017
Contact:

Institutional Ethics Committee-Clinical Studies

Status: Approved
Approval date: 30/11/2017
Contact:

Manavata Clinical Research Insititute Ethics Committee

Status: Approved
Approval date: 01/12/2017
Contact:

Institutional Ethics Committee-Max Super Speciality Hospital

Status: Not Approved
Approval date:
Contact:

Institutional Ethics Committee-TMH