| CTRI Number |
CTRI/2019/09/021333 [Registered on: 19/09/2019] Trial Registered Prospectively |
| Last Modified On: |
27/08/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
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 |
|
Scientific Title of Study
|
A phase II randomized study of the combination of
Ribociclib plus goserelin acetate with Hormonal Therapy
versus physician choice chemotherapy in premenopausal
or perimenopausal patients with hormone receptorpositive/
HER2-negative inoperable locally advanced or
metastatic breast cancer |
| Trial Acronym |
RIGHT Choice Study |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NCT03839823 |
ClinicalTrials.gov |
| CLEE011A3201C-Protocol Version 00 dated 17 Sep 18 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Manish Mistry |
| Designation |
Medical Director (Oncology) |
| Affiliation |
Novartis |
| Address |
Novartis Healthcare Private Limited Trial Monitoring – GDO, GDD India Inspire- BKC, 7th floor, G Block, BKC Main Road Bandra Kurla
Complex Bandra (East)
Mumbai
MAHARASHTRA
400051
India |
| Phone |
9820053069 |
| Fax |
|
| Email |
manish.mistry@novartis.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Manish Mistry |
| Designation |
Medical Director (Oncology) |
| Affiliation |
Novartis |
| Address |
Novartis Healthcare Private Limited Trial Monitoring – GDO, GDD India Inspire- BKC, 7th floor, G Block, BKC Main Road Bandra Kurla
Complex Bandra (East)
Mumbai
MAHARASHTRA
400051
India |
| Phone |
9820053069 |
| Fax |
|
| Email |
manish.mistry@novartis.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Manish Mistry |
| Designation |
Medical Director (Oncology) |
| Affiliation |
Novartis |
| Address |
Novartis Healthcare Private Limited Trial Monitoring – GDO, GDD India Inspire- BKC, 7th floor, G Block, BKC Main Road Bandra Kurla
Complex Bandra (East)
Mumbai
MAHARASHTRA
400051
India |
| Phone |
9820053069 |
| Fax |
|
| Email |
manish.mistry@novartis.com |
|
|
Source of Monetary or Material Support
|
| Novartis Pharma AG, CH-4002 Basel, Switzerland |
|
|
Primary Sponsor
|
| Name |
Novartis Healthcare Pvt Ltd |
| Address |
Trial Monitoring – GDO, GDD India Inspire- BKC, 7th floor, G Block,
BKC Main Road Bandra Kurla Complex Bandra (East)
Mumbai-400051, Maharashtra
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Egypt
India
Jordan
Lebanon
Malaysia
Philippines
Republic of Korea
Saudi Arabia
Singapore
Taiwan
Thailand
Turkey
Viet Nam |
Sites of Study
Modification(s)
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Ajay Gogia |
All India Institute of Medical Sciences |
Department of Medical Oncology, Ansari Nagar, New Delhi-110029
New Delhi
DELHI |
9013000642
ajaygogia@gmail.com |
| Dr Chetan Dilip Deshmukh |
Deenanath Mangeshkar Hospital and Research Center |
1st floor, Oncology Research, Annexe Building, Near Mhatre Bridge, Erandawane, Pune-411004
Pune
MAHARASHTRA |
9850811449
drchetandeshmukh@gmail.com |
| Dr K Govind Babu |
Healthcare Global Enterprises Limited |
Department of Medical Oncology, #44-45/2, 2nd cross Rajaram Mohan Roy Road Exten, Double Road, Bangalore-560027
Bangalore
KARNATAKA |
9845072940
kgblaugh@gmail.com |
| Dr Chanchal Goswami |
Medica Superspecialty Hospital |
Clinical research department, 6th floor, 127, Mukundapur,
E.M.Bypass,
Kolkata-700 099
Kolkata
WEST BENGAL |
9830055035
drcgoswami@gmail.com |
| Dr Meher Lakshmi Konatum |
Nizams Iinstitute of Medical Sciences |
Clinical Trial Unit, Medical Oncology Block, Panjagutta, Hyderabad -500082
Telangana
Hyderabad
TELANGANA |
9440592569
drmeherlak@gmail.com |
| Dr Sudeep Gupta |
Tata Memorial Hospital |
Tata Memorial Hospital, Room No 1109, 11th floor, Homi Bhabha Block, Dr. Ernest Borges Marg, Parel, Mumbai-400 012
Mumbai
MAHARASHTRA |
9821298642
sudeepgupta04@yahoo.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| Clinical Research Ethics Committee-Medica Superspeciality Hospital |
Approved |
| HCG-Central Ethics Committee |
Approved |
| Institute Ethics Committee-AIIMS |
Approved |
| Institutional Ethics Committee-Deenanath Mangeshkar Hospital and Research Center |
Approved |
| Institutional Ethics Committee-Tata Memorial Hospital |
Approved |
| NIMS-Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C50||Malignant neoplasm of breast, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Anastrozole 1 mg |
Daily oral (all 28 days of
every cycle without
interruption). |
| Comparator Agent |
Capecitabine (1600 to
2500 mg/m2/day)along with vinorelbine
(60 to 80 mg/m2 [oral] or
(25 to 30 mg/m2 [IV infusion] |
Capecitabine days 1
to Day 14 twice daily,
followed by a 1-week
rest period, in
3-weeks cycle
Vinorelbine, once, on
Day 1 and Day 8 in
3-weeks cycles |
| Comparator Agent |
Docetaxel(60 to 75 mg/m²)along with capecitabine
(1600 to 2500 mg/m²) |
Docetaxel-IV infusion: once, on day 1 of the 3-weeks
cycle, Capecitabine orally :
twice daily, on Days 1
to 14, followed by a
1-week rest period, in
3 weeks cycle. |
| Intervention |
Goserelin 3.6 mg |
Subcutaneous injection on Day 1 of each 28 day cycle |
| Intervention |
Letrozole 2.5 mg |
Daily oral(all 28 days of
every cycle without
interruption). |
| Comparator Agent |
Paclitaxel (175 mg/m2)along with gemcitabine (1000 to
1250 mg/m2/day) |
Paclitaxel via 3-hour
intravenous (IV)
infusion on Day 1 in
3-weeks cycles.
Gemcitabine at via
30-minute IV infusion
on Day 1 and Day 8
in 3-weeks cycles |
| Comparator Agent |
Paclitaxel (80 to 90 mg/m2)along with gemcitabine
(800 to 1000 mg/m2) |
Paclitaxel via 1 hour
IV infusion on Day 1
and day 8 in 3 weeks cycles.
Gemcitabine at via
30 minute IV infusion on Day 1 and Day 8 in 3 weeks cycles |
| Intervention |
Ribociclib (LEE011) |
Ribociclib oral (3 weeks on/1
week off) |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Female |
| Details |
1. 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.
3. 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.
4. 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.
5. Patient is premenopausal or perimenopausal at the time of study entry.
a. Premenopausal status is defined as either:
• Patient had last menstrual period within the last 12 months.
OR
• 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.
b. 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) |
|
| ExclusionCriteria |
| Details |
1. 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.
2. 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.
3. 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.
4. Patients who have lung metastases with oxygen demand in resting status.
5. 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. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
To determine whether treatment
with NSAI plus goserelin plus ribociclib prolongs PFS compared to treatment with combination chemotherapy in premenopausal or perimenopausal women with
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
|
| Outcome |
TimePoints |
To compare time to treatment
failure between the two
treatment arms. |
Time to treatment failure is defined as the time from the date of randomization start of
treatment to the earliest of date of progression, date of death due to any cause, or date of discontinuation due to
reasons other than Protocol violation or Administrative problems |
To compare patient reported
outcomes for health related quality of life in the two treatment arms |
Change from baseline in the global health status QOL scale score by using FACT B
questionnaires. |
| 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
death due to any cause. |
To determine whether
treatment with NSAI plus goserelin plus ribociclib increases overall
response rate, clinical
benefit rate, and Time to response compared to
treatment with combination
chemotherapy. |
Overall response rate is defined as the proportion of patients whose best overall response is either CR or PR as per local review and according to RECIST 1.1.
Clinical benefit rate is defined as the proportion of patients with a best overall response of CR or PR or stable disease lasting for a duration of at least 24 weeks
Time to response is defined as the time
from the date of randomization to the
first documented response of either CR or PR |
|
|
Target Sample Size
|
Total Sample Size="222"
Sample Size from India="25"
Final Enrollment numbers achieved (Total)= "222"
Final Enrollment numbers achieved (India)="22" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
31/10/2019 |
| Date of Study Completion (India) |
12/01/2023 |
| Date of First Enrollment (Global) |
25/02/2019 |
| Date of Study Completion (Global) |
10/05/2023 |
|
Estimated Duration of Trial
|
Years="3"
Months="10"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
No Publications |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
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 |