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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

NCT03839823

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CLEE011A3201C
  • NCT ID: NCT03839823

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
RibociclibEndocrine treatment arm:, NSAI + goserelin+ ribociclibRibociclib arm
Letrozole OR AnastrozoleEndocrine treatment arm:, NSAI + goserelin+ ribociclibRibociclib arm
GoserelinEndocrine treatment arm:, NSAI + goserelin+ ribociclibRibociclib arm

Purpose

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

      A phase II randomized study of the combination of Ribociclib plus goserelin acetate with
      Hormonal Therapy versus physician choice hemotherapy in premenopausal or perimenopausal
      patients with hormone receptorpositive/ HER2-negative inoperable locally advanced or
      metastatic breast cancer - RIGHT Choice Study
    

Trial Arms

NameTypeDescriptionInterventions
Comparator armActive ComparatorCombination 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.
    Ribociclib armExperimentalCombination 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.
    • Ribociclib
    • Letrozole OR Anastrozole
    • Goserelin

    Eligibility Criteria

            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
    
              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 PI's
                 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.
    
                   1. 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 ≥ 10 pg/mL
                           and/or FSH ≤ 40 IU/l or in the premenopausal range, according to local
                           laboratory definition.
    
                        -  In case of therapy induced amenorrhea, with a plasma estradiol ≥10 pg/mL
                           and/or FSH ≤40 IU/l or in the premenopausal range according to local
                           laboratory definition.
    
                        -  Patients who have undergone bilateral oophorectomy are not eligible.
    
                   2. 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 ≤ 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 disease free
                      interval must be greater than 12 months from the completion of aromatase
                      inhibitor treatment until randomization.
    
                   -  Patients who are receiving ≤ 14 days of tamoxifen or NSAI or LHRH agonists ≤ 28
                      days for advanced breast cancer prior to randomization are eligible.
    
              2. Patient has received extended-field radiotherapy 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.
    
              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.
    
              4. Patients who have lung metastases with oxygen demand in resting status.
    
              5. Patients who have liver metastases with bilirubin > 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
          
    Maximum Eligible Age:59 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression Free Survival
    Time Frame:Up to approximately 12 months
    Safety Issue:
    Description: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

    Measure:Time to treatment failure
    Time Frame:Up to approximately 12 months
    Safety Issue:
    Description: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'.
    Measure:Overall response rate (ORR)
    Time Frame:Up to approximately 12 months
    Safety Issue:
    Description: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.
    Measure:Clinical benefit rate
    Time Frame:Up to approximately 12 months
    Safety Issue:
    Description: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.
    Measure:Time to response
    Time Frame:Up to approximately 12 months
    Safety Issue:
    Description: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.
    Measure:Overall survival
    Time Frame:Up to approximately 44 months
    Safety Issue:
    Description:Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
    Measure:Frequency/severity of adverse events, lab abnormalities.
    Time Frame:Up to approximately 44 months
    Safety Issue:
    Description:Safety of ribociclib in combination with NSAI and goserelin, and combination chemotherapies
    Measure:Change from baseline in the global health status/QOL scale score by using FACT-B questionnaire
    Time Frame:Up to approximately 44 months
    Safety Issue:
    Description: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.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Novartis Pharmaceuticals

    Trial Keywords

    • HR-positive
    • HER2-negative
    • advanced breast cancer
    • Ribociclib
    • NSAI
    • Goserelin
    • Docetaxel / capecitabine
    • Paclitaxel/gemcitabine
    • Capecitabine/vinorelbine
    • CDK4/6
    • Phase II
    • ER-positive
    • PR-positive
    • Premenopausal
    • Perimenopausal.

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