RIGHT Choice: 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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03839823
• Collaborator: (none)
• Enrollment: 223
• Locations: 52
• Arms: 2
• Anticipated Duration (Months): 47
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Combination Product: Docetaxel / Capecitabine; Combination Product: Capecitabine / Vinorelbine; Combination Product: Paclitaxel / Gemcitabine; Drug: Ribociclib; Drug: Letrozole OR Anastrozole; Drug: Goserelin	Phase 2

Detailed Description

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 - RIGHT Choice Study

Study Design

• Study Type: Interventional
• Actual Enrollment: 223 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is 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 will be considered for this studyThis is 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 will be considered for this study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 25, 2019
• Actual Primary Completion Date: Apr 12, 2022
• Anticipated Study Completion Date: Jan 27, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Comparator arm Combination chemotherapies of docetaxel/capecitabine, paclitaxel/gemcitabine or capecitabine/vinorelbine will be administer to patients enrolled in the control group. The chemotherapy regimen will be decided by the treating physician.	Combination Product: Docetaxel / Capecitabine; 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); Other Names: Combination chemotherapy group. The chemotherapy regimen will be decided by the treating physician. ; Combination Product: Capecitabine / Vinorelbine; 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]; Other Names: Combination chemotherapy group. The chemotherapy regimen will be decided by the treating physician. ; Combination Product: Paclitaxel / Gemcitabine; 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); Other Names: Combination chemotherapy group. The chemotherapy regimen will be decided by the treating physician.
Experimental: Ribociclib arm Combination of non-steroidal aromatase inhibitor: NSAI (letrozole or anastrozole) + goserelin + ribociclib. Ribociclib (600 mg) is dosed orally for the first 21 days out of a 28 day cycle. Letrozole (2.5 mg) or anastrozole (1 mg) are dosed orally daily (28 days out of the 28 day cycle). Goserelin (3.6 mg) is 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.	Drug: Ribociclib; Dose: 600 mg (200 mg * 3) Days 1 to 21 of each 28 day cycle Tablets for oral use; Other Names: Endocrine treatment arm: NSAI + goserelin+ ribociclib ; Drug: Letrozole OR Anastrozole; 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.; Other Names: Endocrine treatment arm: NSAI + goserelin+ ribociclib ; Drug: Goserelin; 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; Other Names: Endocrine treatment arm: NSAI + goserelin+ ribociclib

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [Up to approximately 34 months]

   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

1. Time to treatment failure [Up to approximately 34 months]

   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, change to other anti-cancer therapy, or date of discontinuation due to reasons other than 'Protocol violation' or 'Administrative problems'.

2. Overall response rate (ORR) [Up to approximately 34 months]

   Overall response rate (ORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RECIST 1.1.

3. Clinical benefit rate [Up to approximately 34 months]

   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, as defined by RECIST 1.1.

4. Time to response [Up to approximately 34 months]

   Time to response is 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.

5. Overall survival [Up to approximately 46 months]

   Overall survival is defined as the time from the date of randomization to the date of death due to any cause.

6. Frequency/severity of adverse events, lab abnormalities. [Up to approximately 46 months]

   Safety of ribociclib in combination with NSAI and goserelin, and combination chemotherapies

7. Change from baseline in the global health status/QOL scale score by using FACT-B questionnaire [Up to approximately 46 months]

   Functional Assessment of Cancer Therapy - Breast (FACT-B) will be collected to assess health-related QoL, health status, functioning, disease symptoms, side effects, and cancer-related pain. Descriptive statistics will be used to summarize the overall score at each scheduled assessment time point. Additionally, change from baseline at the time of each assessment will be summarized. The distribution of time to definitive 10% deterioration in the global health status from FACT-B questionnaire will be assessed in the two treatment arms. Scores range from 0 to 4. no subscale. 0 score is the worst for social/family and functional wellbeing and 4 is the worst for physical, emotional wellbeing and additional concerns.

8. 3-month treatment failure rate [Up to approximately 34 months]

   Treatment failure rate is defined as the proportion 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 59 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA

1. Patient is an adult female ≥ 18 years old and < 60 years old at the time of informed consent.

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% ER positive or Allred ≥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 inoperable locally advanced 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 PI's judgment. However, for patients who are eligible under inoperable locally advanced breast cancer or criteria 4c, the recruitment is stopped to enrich patient population with visceral metastases.

• 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.

1. Patient is premenopausal or perimenopausal at the time of study entry.

2. 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 and FSH are in the premenopausal range, according to local laboratory definition.

• In case of therapy induced amenorrhea, plasma estradiol and/or FSH are in the premenopausal range according to local laboratory definition.

• Patients who have undergone bilateral oophorectomy are not eligible.

1. Perimenopausal status is defined as neither premenopausal nor postmenopausal

2. Patients must have not 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 are eligible. Patient must have measurable disease.

EXCLUSION CRITERIA;

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 treatment free interval must be greater than 12 months from the completion of aromatase inhibitor treatment until randomization.

• If patients have 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 be greater than 12 months.

• Patients who are receiving ≤ 14 days of tamoxifen or NSAI or LHRH agonists ≤ 28 days for advanced breast cancer prior to randomization are eligible.

1. Patient has received extended-field radiotherapy ≤ 2 weeks prior to randomization or limited field radiotherapy ≤ 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 investigator's discretion). Patient from whom ≥ 25% of the bone marrow has been previously irradiated are also excluded.

2. Patient has 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.

3. Patients who have lung metastases with oxygen demand in resting status.

4. Patients who have liver metastases with bilirubin > 1.5 ULN.

5. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Cairo		Egypt	11566
2	Novartis Investigative Site	Cairo		Egypt	12655
3	Novartis Investigative Site	Cairo		Egypt
4	Novartis Investigative Site	Giza		Egypt	11451
5	Novartis Investigative Site	Bangalore	Karnataka	India	560 095
6	Novartis Investigative Site	Pune	Maharashtra	India	411004
7	Novartis Investigative Site	Hyderabad	Telangana	India	500082
8	Novartis Investigative Site	Kolkata	West Bengal	India	700099
9	Novartis Investigative Site	Mumbai		India	400 012
10	Novartis Investigative Site	New Delhi		India	110029
11	Novartis Investigative Site	Amman		Jordan	11941
12	Novartis Investigative Site	Beirut		Lebanon	1107 2020
13	Novartis Investigative Site	Saida		Lebanon	652
14	Novartis Investigative Site	Tripoli		Lebanon	1434
15	Novartis Investigative Site	Johor Bahru	Johor	Malaysia	81100
16	Novartis Investigative Site	Kota Kinabalu	Sabah	Malaysia	88586
17	Novartis Investigative Site	Kuching	Sarawak	Malaysia	93586
18	Novartis Investigative Site	Kuala Lumpur	Wilayah Persekutuan	Malaysia	50586
19	Novartis Investigative Site	Pulau Pinang		Malaysia	10990
20	Novartis Investigative Site	Moscow		Russian Federation	111123
21	Novartis Investigative Site	Moscow		Russian Federation	115478
22	Novartis Investigative Site	Pushkin Saint Petersburg		Russian Federation	196603
23	Novartis Investigative Site	St Petersburg		Russian Federation	197758
24	Novartis Investigative Site	Riyadh		Saudi Arabia	11211
25	Novartis Investigative Site	Singapore		Singapore	169610
26	Novartis Investigative Site	Singapore		Singapore	188770
27	Novartis Investigative Site	Singapore		Singapore	217562
28	Novartis Investigative Site	Singapore		Singapore	258499
29	Novartis Investigative Site	Durban	Kwazulu Natal	South Africa	4091
30	Novartis Investigative Site	Pretoria		South Africa	0002
31	Novartis Investigative Site	Pretoria		South Africa	0081
32	Novartis Investigative Site	Kaohsiung City		Taiwan	83301
33	Novartis Investigative Site	Taichung		Taiwan	40447
34	Novartis Investigative Site	Tainan		Taiwan	70403
35	Novartis Investigative Site	Taipei		Taiwan	10002
36	Novartis Investigative Site	Taipei		Taiwan	10449
37	Novartis Investigative Site	Taipei		Taiwan	11217
38	Novartis Investigative Site	Taipei		Taiwan	114
39	Novartis Investigative Site	Taoyuan		Taiwan	33305
40	Novartis Investigative Site	Songkhla	Hat Yai	Thailand	90110
41	Novartis Investigative Site	Bangkok		Thailand	10310
42	Novartis Investigative Site	Bangkok		Thailand	10400
43	Novartis Investigative Site	Chiang Mai		Thailand	50200
44	Novartis Investigative Site	Ankara		Turkey	06520
45	Novartis Investigative Site	Antalya		Turkey	07059
46	Novartis Investigative Site	Cankaya Ankara		Turkey	06560
47	Novartis Investigative Site	Istanbul		Turkey	34381
48	Novartis Investigative Site	Istanbul		Turkey	34457
49	Novartis Investigative Site	Izmir		Turkey	35040
50	Novartis Investigative Site	Kecioren Ankara		Turkey	06010
51	Novartis Investigative Site	Malatya		Turkey	44280
52	Novartis Investigative Site	Hanoi		Vietnam	100000

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03839823
• Other Study ID Numbers: CLEE011A3201C
• First Posted: Feb 15, 2019
• Last Update Posted: Jun 30, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: 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
• Additional relevant MeSH terms: Breast Neoplasms; Gemcitabine; Paclitaxel; Vinorelbine; Docetaxel; Capecitabine; Letrozole; Anastrozole; Goserelin

Study Results

No Results Posted as of Jun 30, 2022