Comparing the combination of Ribociclib plus goserelin acetate with hormonal therapy versus combination chemotherapy in premenopausal or perimenopausal patients with advanced or metastatic breast cancer

Phase 2

Completed

Conditions: Malignant neoplasm of breast,

Registration Number: CTRI/2019/09/021333

Lead Sponsor: Novartis Healthcare Pvt Ltd

Brief Summary: Purpose of the trial: Recent phase III clinical trials demonstrated that CDK4/6 inhibitor plus endocrine therapy could generate a tumor response rate higher than 50% (in measurable lesions), which is higher than what has been reported by

most of the chemotherapy regimens in phase III studies. The purpose of this trial is to compare the two treatment modalities in the patients with aggressive disease in HR+/HER2- metastatic pre/peri-menopausal breast

cancer setting.

FPFV for India: May 2019

No of Patients from India: 25

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Female

Target Recruitment: 222

Inclusion Criteria

Patient is an adult female 18 years old to 60 years old at the time of informed consent.
Written informed consent must be obtained prior to any screening procedures 2.
Patient has a histologically and or cytologically confirmed diagnosis of estrogen receptor positive and or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory.
ER should be more than 10 percent ER positive or Allred more than or equal to 5 by local laboratory testing.
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.
Women with advanced locoregionally recurrent or metastatic breast cancer not amenable to curative therapy.
Patients must fulfill at least one of the following criteria to be considered that combination chemotherapy is needed according to PIs judgment Symptomatic visceral metastases Rapid progression of disease or impending visceral compromise.
Markedly symptomatic non visceral disease if the treating physician opt to give chemotherapy for rapid palliation of patients symptoms.
Patient is premenopausal or perimenopausal at the time of study entry.
Premenopausal status is defined as either: â€¢ Patient had last menstrual period within the last 12 months.
OR â€¢ If on tamoxifen within the past 14 days, plasma estradiol must be more than 10 pg/mL and or FSH less than 40 IU/l or in the premenopausal range, according to local laboratory definition.
In case of therapy induced amenorrhea, with a plasma estradiol more than 10 pg/mL and or FSH less than 40 IU/l or in the premenopausal range according to local laboratory definition.
Patients who have undergone bilateral oophorectomy are not eligible.
Perimenopausal status is defined as neither premenopausal nor postmenopausal 6.
Patients must have not received any prior hormonal therapy and chemotherapy for advanced breast cancer, except LHRH agonist.
Patients who received less than 14 days of tamoxifen or a NSAI (letrozole or anastrozole) with or without LHRH agonist for advanced breast cancer prior to randomization are eligible.
Patient must have measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is a clear sign of progression since the irradiation).

Exclusion Criteria

Patient has received prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy, or any CDK4 6 inhibitor for advanced breast cancer.
Patients who received (neo) adjuvant therapy for breast cancer are eligible.
If the prior neo (adjuvant) therapy included aromatase inhibitors, the disease free interval must be greater than 12 months from the completion of aromatase inhibitor treatment until randomization.
Patients who are receiving less than 14 days of tamoxifen or NSAI or LHRH agonists less than 28 days for advanced breast cancer prior to randomization are eligible.
Patient has received extended field radiotherapy or limited field radiotherapy less than 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 investigators discretion.
Patient from whom more than 25 percent of the bone marrow has been previously irradiated are also excluded.
Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated basal or squamous cell skin carcinoma non melanomatous skin cancer or curatively resected cervical cancer.
Note CNS involvement must be ruled out by assessments if a patient has any signs or symptoms indicating potential central nervous system metastases.
Patients who have lung metastases with oxygen demand in resting status.
Patients who have liver metastases with bilirubin more than 1.5 mg/dL 6.
Patients with CNS involvement unless they meet ALL of the following criteria 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.
Leptomeningeal metastases is not allowed, even with stable clinical condition.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine whether treatment	Progression-free survival is defined as the \| time from the date of randomization to the \| date of the first documented progression as \| per local review and according to RECIST \| 1.1 or death due to any cause.
with NSAI plus goserelin plus ribociclib prolongs PFS compared to treatment with combination chemotherapy in premenopausal or perimenopausal women with	Progression-free survival is defined as the \| time from the date of randomization to the \| date of the first documented progression as \| per local review and according to RECIST \| 1.1 or death due to any cause.
HR positive, HER2 negative locally advanced or metastatic breast cancer.	Progression-free survival is defined as the \| time from the date of randomization to the \| date of the first documented progression as \| per local review and according to RECIST \| 1.1 or death due to any cause.

Secondary Outcome Measures

Name	Time	Method
To compare time to treatment	failure between the two
To compare patient reported	outcomes for health related quality of life in the two treatment arms
To evaluate the safety of ribociclib in combination with NSAI and goserelin and combination chemotherapies	Frequency severity of adverse events lab abnormalities.
To compare the overall survival between two treatment arms.	Overall survival is defined as the time from the date of randomization to the date of
To determine whether	treatment with NSAI plus goserelin plus ribociclib increases overall

Trial Locations

Locations (6): All India Institute of Medical Sciences
🇮🇳
Delhi, DELHI, India
Deenanath Mangeshkar Hospital and Research Center
🇮🇳
Pune, MAHARASHTRA, India
Healthcare Global Enterprises Limited
🇮🇳
Bangalore, KARNATAKA, India
Medica Superspecialty Hospital
🇮🇳
Kolkata, WEST BENGAL, India
Nizams Iinstitute of Medical Sciences
🇮🇳
Hyderabad, TELANGANA, India
Tata Memorial Hospital
🇮🇳
Mumbai, MAHARASHTRA, India
All India Institute of Medical Sciences
🇮🇳Delhi, DELHI, India
Dr Ajay Gogia
Principal investigator
9013000642
ajaygogia@gmail.com