Breast CancerPhase 2RIGHT ChoiceNCT03839823
Study to Compare the Combination of Ribociclib Plus Goserelin Acetate With Hormonal Therapy Versus Combination Chemotherapy in Premenopausal or Perimenopausal Patients With Advanced or Metastatic Breast Cancer
A Phase 2 study testing Docetaxel / Capecitabine, Capecitabine / Vinorelbine and Paclitaxel / Gemcitabine in people with Breast Cancer, run by Novartis Pharmaceuticals at 50 sites in 13 countries.
Trial summary
To compare the combination of Ribociclib plus goserelin acetate with hormonal therapy versus combination chemotherapy in premenopausal or perimenopausal patients with advanced or metastatic breast cancer Read more about this study
- Who is it for?
- Ages 18 to 59 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Docetaxel / Capecitabine, Capecitabine / Vinorelbine and Paclitaxel / Gemcitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- 50 sitesin 13 countries
- Study dates
- 25 Feb 2019to 10 May 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 59 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Patient was an adult female ≥ 18 years old and < 60 years old at the time of informed consent.
- Patient had 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 have been more than 10% ER positive or Allred ≥5 by local laboratory testing.
- Patient had 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 was required by local laboratory testing and based on the most recently analyzed tissue sample.
- Women with inoperable locally advanced or metastatic breast cancer not amenable to curative therapy. Patients had to fulfill at least one of the following criteria to be considered that combination chemotherapy was needed according to PI's judgment. However, for patients who were eligible under inoperable locally advanced breast cancer or criteria 4c, the recruitment was stopped to enrich patient population with visceral metastases.
- Symptomatic visceral metastases
- Rapid progression of disease or impending visceral compromise.
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- Markedly symptomatic non-visceral disease if the treating physician opted to give chemotherapy for rapid palliation of patient's symptoms.
- Patient was premenopausal or perimenopausal at the time of study entry.
- Premenopausal status was defined as either:
- Patient had last menstrual period within the last 12 months. OR
- If on tamoxifen within the past 14 days, plasma estradiol and FSH were in the premenopausal range, according to local laboratory definition.
- In case of therapy induced amenorrhea, plasma estradiol and/or FSH were in the premenopausal range according to local laboratory definition.
- Patients who had undergone bilateral oophorectomy were not eligible.
- Perimenopausal status was defined as neither premenopausal nor postmenopausal.
- Patients had received neither prior hormonal therapy nor chemotherapy for advanced breast cancer, except LHRH agonist. Patients who received ≤ 14 days of tamoxifen or a NSAI (letrozole or anastrozole) with or without LHRH agonist for advanced breast cancer prior to randomization were eligible. Patient had measurable disease.
Who cannot join
- Patient 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 were eligible. If the prior neo (adjuvant) therapy included aromatase inhibitors, the treatment-free interval must have been greater than 12 months from the completion of aromatase inhibitor treatment until randomization.
- If patients had disease recurrence during adjuvant tamoxifen treatment, disease-free interval (defined as duration between the date of patient received complete tumor resection for primary breast cancer lesion to the date of disease recurrence documented) must have been greater than 12 months.
- Patients who were receiving ≤ 14 days of tamoxifen or NSAI or LHRH agonists ≤ 28 days for advanced breast cancer prior to randomization were eligible.
- Patient had received extended-field radiotherapy ≤ 2 weeks prior to randomization or limited field radiotherapy ≤ 2 weeks prior to randomization, and had 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 from whom ≥ 25% of the bone marrow had been previously irradiated were also excluded.
- Patient had a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ.
Show all 12Show fewer
- Patients who had lung metastases with oxygen demand in resting status.
- Patients who had liver metastases with bilirubin > 1.5 ULN.
- Patients with CNS involvement unless they met 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 was not allowed, even with stable clinical condition.
Trial locations and contacts
50 sites in 13 countries.
50 sites in 13 countries
Taiwan8 sites
Novartis Investigative Site
Kaohsiung City, 83301
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Tainan, 70403
Novartis Investigative Site
Taipei, 10002
Novartis Investigative Site
Taipei, 10449
Novartis Investigative Site
Taipei, 11217
Novartis Investigative Site
Taipei, 114
Novartis Investigative Site
Taoyuan, 33305
Turkey (Türkiye)7 sites
Novartis Investigative Site
Ankara, 06520
Novartis Investigative Site
Antalya, 07059
Novartis Investigative Site
Cankaya Ankara, Turkey, 06560
Novartis Investigative Site
Istanbul, 34381
Novartis Investigative Site
Izmir, 35040
Novartis Investigative Site
Kecioren Ankara, Turkey, 06010
Novartis Investigative Site
Malatya, 44280
India6 sites
Novartis Investigative Site
Bangalore, Karnataka, 560 095
Novartis Investigative Site
Hyderabad, Telangana, 500082
Novartis Investigative Site
Kolkata, West Bengal, 700099
Novartis Investigative Site
Mumbai, 400 012
Novartis Investigative Site
New Delhi, 110029
Novartis Investigative Site
Pune, Maharashtra, 411004
Malaysia5 sites
Novartis Investigative Site
Johor Bahru, Johor, 81100
Novartis Investigative Site
Kota Kinabalu, Sabah, 88586
Novartis Investigative Site
Kuala Lumpur, Kuala Lumpur, 50586
Novartis Investigative Site
Kuching, Sarawak, 93586
Novartis Investigative Site
Pulau Pinang, 10990
Egypt4 sites
Novartis Investigative Site
Cairo, 11566
Novartis Investigative Site
Cairo, 12655
Novartis Investigative Site
Cairo, 3247511
Novartis Investigative Site
Giza, 11451
Russia4 sites
Novartis Investigative Site
Moscow, 111123
Novartis Investigative Site
Moscow, 115478
Novartis Investigative Site
Pushkin Saint Petersburg, 196603
Novartis Investigative Site
Saint Petersburg, 197758
Thailand4 sites
Novartis Investigative Site
Bangkok, 10310
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Chiang Mai, 50200
Novartis Investigative Site
Songkhla, Hat Yai, 90110
Lebanon3 sites
Novartis Investigative Site
Beirut, 1107 2020
Novartis Investigative Site
Saida, 652
Novartis Investigative Site
Tripoli, 1434
Singapore3 sites
Novartis Investigative Site
Singapore, 168583
Novartis Investigative Site
Singapore, 188770
Novartis Investigative Site
Singapore, 258499
South Africa3 sites
Novartis Investigative Site
Durban, KwaZulu-Natal, 4091
Novartis Investigative Site
Pretoria, 0002
Novartis Investigative Site
Pretoria, 0081
About this study
Official title: 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 Receptor-positive/ HER2-negative Inoperable Locally Advanced or Metastatic Breast Cancer
To compare the combination of Ribociclib plus goserelin acetate with hormonal therapy versus combination chemotherapy in premenopausal or perimenopausal patients with advanced or metastatic breast cancer
Read the detailed description
Patients were randomly assigned to one of the below treatment arms in 1:1 ratio:
- Ribociclib arm: non-steroidal aromatase inhibitor (NSAI) + goserelin + Ribociclib
- Combination chemotherapy arm: Either of docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine based chemotherapy treatment Randomization was stratified by (1) the presence of liver metastases (present or absent) (2) disease-free interval (DFI) < 2 years (yes or no, de novo stage 4 was defined as DFI > 2 years).
The study consisted of a 28-day Screening phase, treatment phase (including end of treatment (EOT) visit and safety follow-up), and survival follow-up. Patients received study treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.
Patients were followed for survival regardless of treatment discontinuation for any reason (except if consent was withdrawn, patient was lost to follow-up, or until death) and regardless of achieving the primary endpoint, until death, withdrawal of consent, or loss to follow-up.
- Conditions
- Breast Cancer
- Being tested
- Docetaxel / Capecitabine, Capecitabine / Vinorelbine, Paclitaxel / Gemcitabine, Ribociclib, Letrozole OR Anastrozole
- Keywords
- HR-positive, HER2-negative, advanced breast cancer, Ribociclib, NSAI, Goserelin, Docetaxel / capecitabine, Paclitaxel/gemcitabine, Capecitabine/vinorelbine, CDK4/6 inhibitors, Phase II, ER-positive, PR-positive, Premenopausal, Perimenopausal
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Docetaxel / CapecitabineCombination product
Also called Combination chemotherapy group., The chemotherapy regimen was decided by the treating physician.
Docetaxel (IV Infusion) / Capecitabine (Tablets for oral use):
Docetaxel once, on day 1 of the 3-weeks cycle. Capecitabine twice daily, on Days 1 to 14, followed by a 1-week rest period, in 3 weeks cycle.
Docetaxel (60 - 75 mg/m²)/capecitabine (1600 - 2500 mg/m²/day)
Capecitabine / VinorelbineCombination product
Also called Combination chemotherapy group., The chemotherapy regimen was decided by the treating physician.
Capecitabine (Tablets for oral use) / Vinorelbine (Capsule for Oral use/IV infusion ).
Capecitabine twice daily on day 1 to 14, followed by a 1-week rest period, in 3 weeks cycle.
Vinorelbine, once, on Day 1 and Day 8 in 3 weeks cycles.
Capecitabine (1600 - 2500 mg/m2/day)/vinorelbine (60 to 80 mg/m2/day [oral] or (25 to 30 mg/m2 [IV infusion]
Paclitaxel / GemcitabineCombination product
Also called Combination chemotherapy group., The chemotherapy regimen was decided by the treating physician.
Paclitaxel (IV Infusion) / Gemcitabine (IV Infusion):
Paclitaxel via 3-hour intravenous (IV) infusion on Day 1 in 3-weeks cycles, OR Paclitaxel via 1 hour intravenous (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.
Paclitaxel (175 mg/m2) (on Day 1 in 3-weeks cycles)/ gemcitabine (1000 - 1250 mg/m2)
OR
Paclitaxel (80 - 90 mg/m2) (on Day 1 and Day 8 in 3-weeks cycles) / gemcitabine (800 - 1250 mg/m2)
RibociclibDrug
Also called Endocrine treatment arm:, NSAI + goserelin+ ribociclib
Dose: 600 mg (200 mg * 3) Days 1 to 21 of each 28 day cycle Tablets for oral use
Letrozole OR AnastrozoleDrug
Also called Endocrine treatment arm:, NSAI + goserelin+ ribociclib
Letrozole:
Dose: 2.5 mg All days of every cycle without interruption). Tablets for oral use
Anastrozole:
dose: 1 mg All days of every cycle without interruption. Tablets for oral use
The NSAI (letrozole or anastrozole) will be decided by the treating physician.
GoserelinDrug
Also called Endocrine treatment arm:, NSAI + goserelin+ ribociclib
Dose: 3.6 mg Day 1 of each 28 day cycle (regardless of ribociclib treatment cycle) with an administration window of + 3 days.
Subcutaneous implant
| Study group | Role | What they receive |
|---|---|---|
| Ribociclib 600 mg | Experimental | Combination of non-steroidal aromatase inhibitor: NSAI (letrozole or anastrozole) + goserelin + ribociclib.
1. Ribociclib (600 mg) was dosed orally for the first 21 days out of a 28-day cycle.
2. Letrozole (2.5 mg) or anastrozole (1 mg) were dosed orally daily (28 days out of the 28-day cycle).
3. Goserelin (3.6 mg) was continuously released via a subcutaneous implant injected on Day 1 of each 28-day cycle (regardless of ribociclib treatment cycle) with an administration window of + 3 days. Receives: Drug: Ribociclib; Drug: Letrozole OR Anastrozole; Drug: Goserelin |
| Combination Chemotherapy | Active comparator | Combination chemotherapies of docetaxel/capecitabine, paclitaxel/gemcitabine or capecitabine/vinorelbine were administered to patients enrolled in the control group. The chemotherapy regimen was decided by the treating physician. Receives: Combination Product: Docetaxel / Capecitabine; Combination Product: Capecitabine / Vinorelbine; Combination Product: Paclitaxel / Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Progression-free survival was 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. PFS was censored at the date of the last adequate tumor assessment if no PFS event was observed at the time of last patient, last visit (LPLV).
Measured: Up to approximately 34 months
Secondary outcomes (10)
Time to Treatment Failure
Time to treatment failure was 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, change to other anti-cancer therapy, or date of discontinuation due to reasons other than 'Protocol violation' or 'Administrative problems'. Patients who did not achieve a confirmed PR or CR were censored at: the maximum follow-up time (i.e., LPLV - first patient first visit [FPFV] used for the analysis) for patients who had a PFS event (i.e., either progressed or died due to any cause); the last adequate tumor assessment date for all other patients.
Measured: Up to approximately 34 months
3-month Treatment Failure Rate
Treatment failure rate was defined as the percentage of patients who discontinued the study treatment due to progressive disease, death due to any cause, change to other anti-cancer therapy, or discontinuation due to reasons other than protocol violation or administrative problems.
Measured: Up to approximately 3 months
Overall Response Rate (ORR)
Overall response rate (ORR) was defined as the percentage of patients with a best overall response (BOR) of complete response (CR) or partial response (PR, response without image confirmation), as per local review and according to RECIST 1.1.
Measured: Up to approximately 34 months
Clinical Benefit Rate
Clinical benefit rate was defined as the percentage of patients with a BOR of CR, PR, or stable disease (SD, response without image confirmation) lasting 24 weeks or longer, as defined by RECIST 1.1.
Measured: Up to approximately 34 months
Time to Response
Time to response was defined as the time from the date of randomization to the first documented response of either CR or PR, which must be subsequently confirmed, as defined by RECIST 1.1. Patients who did not achieve a confirmed PR or CR were censored at: the maximum follow-up time (i.e., LPLV - FPFV used for the analysis) for patients who had a PFS event (i.e., either progressed or died due to any cause); the last adequate tumor assessment date for all other patients.
Measured: Up to approximately 34 months
Overall Survival (OS)
Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a patient was not known to have died at the time of LPLV, then OS was censored at the last contact date.
Measured: Up to approximately 46 months
Change From Baseline in the Global Health Status/Quality of Life (QOL) Scale Score by Using the Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire
FACT-B is a self-reported instrument that measures multidimensional quality of life (QOL) in patients with breast cancer. The FACT-B consists of 37 questions that address physical, social, emotional, and functional well-being, with specific questions relevant to women with breast cancer. Each item has a score range of 0 (Not at all) to 4 (Very much), with a total score ranging from 0-148. The higher the score, the better the QOL reported by the participant. A positive change from baseline indicates improvement in QoL.
Measured: Up to approximately 46 months
Number of Patients With Adverse Events, Categorized by Severity
Adverse events were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or higher. If CTCAE grading did not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to Grades 1 - 4, were used. A patient with multiple severity grades for an AE was only counted under the maximum grade. Data for Grades 3 and 4 are reported.
Measured: Up to approximately 46 months
Number of Patients With Laboratory Abnormalities
Grading of laboratory values was assigned programmatically as per NCI Common Terminology Criteria for Adverse Events (CTCAE) version available at the time of analysis. The calculation of CTCAE grades was based on the observed laboratory values only, clinical assessments were not be taken into account. CTCAE Grade 0 was assigned for all non-missing values not graded as 1 or higher. Grade 5 was not used. For laboratory tests where grades were not defined by CTCAE available at the time of analysis, results were categorized as low/normal/high based on laboratory normal ranges.
Measured: Up to approximately 46 months
Post-Hoc: All Collected Deaths
On-treatment deaths due to any cause were collected from first dose of study medication to 30 days after the last dose of study treatment. Post-treatment survival follow-up deaths were collected from day 31 after last dose of study medication to end of study.
Measured: On-treatment deaths: Up to approximately 46 months. Post-treatment survival follow-up deaths: Up to approximately 2 additional months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start25 Feb 2019
- Primary completion12 Apr 2022
- Study completion10 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This was a randomized, phase II, open label, multi-center trial comparing the combination of NSAI (letrozole or anastrozole) + goserelin + ribociclib versus combination chemotherapy (either of docetaxel/capecitabine or paclitaxel/gemcitabine or capecitabine/vinorelbine). Premenopausal or perimenopausal women with HR+, HER2- negative, advanced breast cancer with ECOG performance status of 0 to 2 and having symptomatic visceral metastases, or rapid progression of disease or impending visceral compromise, or markedly symptomatic non visceral disease were considered for this study.
- Masking
- None (open label)
- Enrolment
- 222 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03839823
- Sponsor's protocol ID
- CLEE011A3201C
- Acronym
- RIGHT Choice
- Status last verified
- Oct 2024
- First submitted
- 24 Jan 2019
- Last updated
- 9 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Lu YS, Mahidin EIBM, Azim H, Eralp Y, Yap YS, Im SA, Rihani J, Gokmen E, El Bastawisy A, Karadurmus N, Lim YN, Lim CS, Duc LT, Chung WP, Babu KG, Penkov K, Bowles J, Alfaro TD, Wu J, Gao M, Slimane K, El Saghir NS. Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. J Clin Oncol. 2024 Aug 10;42(23):2812-2821. doi: 10.1200/JCO.24.00144. Epub 2024 May 21.
PubMed 38771995
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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 Receptor-positive/ HER2-negative Inoperable Locally Advanced or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT03839823
- Acronym / sponsor ID
- RIGHT Choice / CLEE011A3201C
- Conditions
- Breast Cancer
- Keywords
- HR-positive, HER2-negative, advanced breast cancer, Ribociclib, NSAI, Goserelin, Docetaxel / capecitabine, Paclitaxel/gemcitabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 222 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Feb 2019 (actual)
- Primary completion
- 12 Apr 2022 (actual)
- Study completion
- 10 May 2023 (actual)
- First posted
- 15 Feb 2019 (actual)
- Results
- Posted 20 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare the combination of Ribociclib plus goserelin acetate with hormonal therapy versus combination chemotherapy in premenopausal or perimenopausal patients with advanced or metastatic breast cancer
Detailed description
Patients were randomly assigned to one of the below treatment arms in 1:1 ratio:
- Ribociclib arm: non-steroidal aromatase inhibitor (NSAI) + goserelin + Ribociclib
- Combination chemotherapy arm: Either of docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine based chemotherapy treatment Randomization was stratified by (1) the presence of liver metastases (present or absent) (2) disease-free interval (DFI) < 2 years (yes or no, de novo stage 4 was defined as DFI > 2 years).
The study consisted of a 28-day Screening phase, treatment phase (including end of treatment (EOT) visit and safety follow-up), and survival follow-up. Patients received study treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.
Patients were followed for survival regardless of treatment discontinuation for any reason (except if consent was withdrawn, patient was lost to follow-up, or until death) and regardless of achieving the primary endpoint, until death, withdrawal of consent, or loss to follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This was a randomized, phase II, open label, multi-center trial comparing the combination of NSAI (letrozole or anastrozole) + goserelin + ribociclib versus combination chemotherapy (either of docetaxel/capecitabine or paclitaxel/gemcitabine or capecitabine/vinorelbine). Premenopausal or perimenopausal women with HR+, HER2- negative, advanced breast cancer with ECOG performance status of 0 to 2 and having symptomatic visceral metastases, or rapid progression of disease or impending visceral compromise, or markedly symptomatic non visceral disease were considered for this study.
| Arm | Type | Receives |
|---|---|---|
| Ribociclib 600 mg | Experimental | Drug: Ribociclib, Drug: Letrozole OR Anastrozole, Drug: GoserelinCombination of non-steroidal aromatase inhibitor: NSAI (letrozole or anastrozole) + goserelin + ribociclib. 1. Ribociclib (600 mg) was dosed orally for the first 21 days out of a 28-day cycle. 2. Letrozole (2.5 mg) or anastrozole (1 mg) were dosed orally daily (28 days out of the 28-day cycle). 3. Goserelin (3.6 mg) was continuously released via a subcutaneous implant injected on Day 1 of each 28-day cycle (regardless of ribociclib treatment cycle) with an administration window of + 3 days. |
| Combination Chemotherapy | Active comparator | Combination Product: Docetaxel / Capecitabine, Combination Product: Capecitabine / Vinorelbine, Combination Product: Paclitaxel / GemcitabineCombination chemotherapies of docetaxel/capecitabine, paclitaxel/gemcitabine or capecitabine/vinorelbine were administered to patients enrolled in the control group. The chemotherapy regimen was decided by the treating physician. |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Patient was an adult female ≥ 18 years old and < 60 years old at the time of informed consent.
- Patient had 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 have been more than 10% ER positive or Allred ≥5 by local laboratory testing.
- Patient had 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 was required by local laboratory testing and based on the most recently analyzed tissue sample.
- Women with inoperable locally advanced or metastatic breast cancer not amenable to curative therapy. Patients had to fulfill at least one of the following criteria to be considered that combination chemotherapy was needed according to PI's judgment. However, for patients who were eligible under inoperable locally advanced breast cancer or criteria 4c, the recruitment was stopped to enrich patient population with visceral metastases.
- Patient was premenopausal or perimenopausal at the time of study entry.
Key exclusion criteria (12 listed)
- Patient received prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy, or any CDK4/6 inhibitor for advanced breast cancer).
- Patient had received extended-field radiotherapy ≤ 2 weeks prior to randomization or limited field radiotherapy ≤ 2 weeks prior to randomization, and had 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 from whom ≥ 25% of the bone marrow had been previously irradiated were also excluded.
- Patient had a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ.
- Patients who had lung metastases with oxygen demand in resting status.
- Patients who had liver metastases with bilirubin > 1.5 ULN.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Docetaxel / CapecitabineAlso: Combination chemotherapy group., The chemotherapy regimen was decided by the treating physician.Docetaxel (IV Infusion) / Capecitabine (Tablets for oral use): Docetaxel once, on day 1 of the 3-weeks cycle. Capecitabine twice daily, on Days 1 to 14, followed by a 1-week rest period, in 3 weeks cycle. Docetaxel (60 - 75 mg/m²)/capecitabine (1600 - 2500 mg/m²/day) | Combination product | Combination Chemotherapy |
| Capecitabine / VinorelbineAlso: Combination chemotherapy group., The chemotherapy regimen was decided by the treating physician.Capecitabine (Tablets for oral use) / Vinorelbine (Capsule for Oral use/IV infusion ). Capecitabine twice daily on day 1 to 14, followed by a 1-week rest period, in 3 weeks cycle. Vinorelbine, once, on Day 1 and Day 8 in 3 weeks cycles. Capecitabine (1600 - 2500 mg/m2/day)/vinorelbine (60 to 80 mg/m2/day [oral] or (25 to 30 mg/m2 [IV infusion] | Combination product | Combination Chemotherapy |
| Paclitaxel / GemcitabineAlso: Combination chemotherapy group., The chemotherapy regimen was decided by the treating physician.Paclitaxel (IV Infusion) / Gemcitabine (IV Infusion): Paclitaxel via 3-hour intravenous (IV) infusion on Day 1 in 3-weeks cycles, OR Paclitaxel via 1 hour intravenous (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. Paclitaxel (175 mg/m2) (on Day 1 in 3-weeks cycles)/ gemcitabine (1000 - 1250 mg/m2) OR Paclitaxel (80 - 90 mg/m2) (on Day 1 and Day 8 in 3-weeks cycles) / gemcitabine (800 - 1250 mg/m2) | Combination product | Combination Chemotherapy |
| RibociclibAlso: Endocrine treatment arm:, NSAI + goserelin+ ribociclibDose: 600 mg (200 mg * 3) Days 1 to 21 of each 28 day cycle Tablets for oral use | Drug | Ribociclib 600 mg |
| Letrozole OR AnastrozoleAlso: Endocrine treatment arm:, NSAI + goserelin+ ribociclibLetrozole: Dose: 2.5 mg All days of every cycle without interruption). Tablets for oral use Anastrozole: dose: 1 mg All days of every cycle without interruption. Tablets for oral use The NSAI (letrozole or anastrozole) will be decided by the treating physician. | Drug | Ribociclib 600 mg |
| GoserelinAlso: Endocrine treatment arm:, NSAI + goserelin+ ribociclibDose: 3.6 mg Day 1 of each 28 day cycle (regardless of ribociclib treatment cycle) with an administration window of + 3 days. Subcutaneous implant | Drug | Ribociclib 600 mg |
Primary outcome
Progression-free Survival
Time frame: Up to approximately 34 months
Progression-free survival was 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. PFS was censored at the date of the last adequate tumor assessment if no PFS event was observed at the time of last patient, last visit (LPLV).
10 secondary outcomes
Time to Treatment Failure
Time frame: Up to approximately 34 months
3-month Treatment Failure Rate
Time frame: Up to approximately 3 months
Overall Response Rate (ORR)
Time frame: Up to approximately 34 months
Clinical Benefit Rate
Time frame: Up to approximately 34 months
Time to Response
Time frame: Up to approximately 34 months
Overall Survival (OS)
Time frame: Up to approximately 46 months
Change From Baseline in the Global Health Status/Quality of Life (QOL) Scale Score by Using the Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire
Time frame: Up to approximately 46 months
Number of Patients With Adverse Events, Categorized by Severity
Time frame: Up to approximately 46 months
Number of Patients With Laboratory Abnormalities
Time frame: Up to approximately 46 months
Post-Hoc: All Collected Deaths
Time frame: On-treatment deaths: Up to approximately 46 months. Post-treatment survival follow-up deaths: Up to approximately 2 additional months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38771995Lu YS, Mahidin EIBM, Azim H, Eralp Y, Yap YS, Im SA, Rihani J, Gokmen E, El Bastawisy A, Karadurmus N, Lim YN, Lim CS, Duc LT, Chung WP, Babu KG, Penkov K, Bowles J, Alfaro TD, Wu J, Gao M, Slimane K, El Saghir NS. Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. J Clin Oncol. 2024 Aug 10;42(23):2812-2821. doi: 10.1200/JCO.24.00144. Epub 2024 May 21.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
50 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docetaxel / Capecitabine, Capecitabine / Vinorelbine and Paclitaxel / Gemcitabine in people with Breast Cancer, run by Novartis Pharmaceuticals at 50 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in Taiwan, Turkey (Türkiye), India, Malaysia, Egypt and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (time frame: Up to approximately 34 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03839823, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2024.