Clinical Trials /

Study for Women and Men With Hormone-receptor Positive Locally Advanced or Metastatic Breast Cancer

NCT03096847

Description:

This was a national, multi-center, open-label, phase IIIb trial to determine the efficacy and safety of treatment with ribociclib (LEE011) plus letrozole in patients with HR+, HER2-negative advanced (recurrent or metastatic) breast cancer. Patients were treated with daily doses of 600 mg ribociclib (3-weeks-on/1-week-off schedule) in combination with 2.5 mg letrozole daily (continuous dosing). Dose adjustments (dose reduction or interruption) according to safety findings were allowed.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT03096847

Trial Eligibility

Document

Title

  • Brief Title: Study for Women and Men With Hormone-receptor Positive Locally Advanced or Metastatic Breast Cancer
  • Official Title: A National Phase IIIb, Multi-center, Open Label Study for Women and Men With Hormone-receptor Positive, HER-2 Negative Locally Advanced or Metastatic Breast Cancer Treated With Ribociclib (LEE011) in Combination With Letrozole

Clinical Trial IDs

  • ORG STUDY ID: CLEE011XDE01
  • SECONDARY ID: CLEE011XDE01
  • SECONDARY ID: 2016-002556-24
  • NCT ID: NCT03096847

Conditions

  • Advanced Metastatic Breast Cancer

Interventions

DrugSynonymsArms
ribociclibLEE011ribociclib + letrozole cohort A
letrozoleribociclib + letrozole cohort A
goserelinribociclib + letrozole cohort A

Purpose

This was a national, multi-center, open-label, phase IIIb trial to determine the efficacy and safety of treatment with ribociclib (LEE011) plus letrozole in patients with HR+, HER2-negative advanced (recurrent or metastatic) breast cancer. Patients were treated with daily doses of 600 mg ribociclib (3-weeks-on/1-week-off schedule) in combination with 2.5 mg letrozole daily (continuous dosing). Dose adjustments (dose reduction or interruption) according to safety findings were allowed.

Detailed Description

      The main purpose of this study was to collect additional efficacy and safety data for the
      combination of ribociclib and letrozole in a patient population broader than the MONALEESA-2
      study (NCT01958021 / CLEE011A2301), and to provide access to ribociclib to patients for which
      available treatment options are unsatisfactory treatment alternatives until the drug is
      approved for this indication. Furthermore, this trial aimed to collect data for the
      combination of ribociclib and letrozole in the context of current local routine therapy
      algorithms for the treatment of metastatic and advanced breast cancer.

      This multi-center, open-label, single-arm study aimed to evaluate the efficacy, safety, and
      quality of life for the combination of ribociclib and letrozole in a patient population than
      in the MONALEESA-2 study, i.e. in patients pretreated with one line of chemotherapy and/or a
      maximum of two lines of endocrine therapy as well as premenopausal patients, without
      limitations regarding the disease free interval after adjuvant therapy.

      For ethical reasons no endocrine comparator drugs were investigated in this study. The
      duration of study treatment of 80 weeks was adequate to determine the primary, secondary and
      exploratory study parameters. The sample size was suitable to estimate the clinical benefit
      rate (CBR) in this patient population with reasonable precision.

      Goserelin was used in premenopausal patients, since it was shown that ovarian suppression of
      estrogen release with luteinizing hormone-releasing hormone agonists (LHRHa) (such as
      goserelin) is effective in preventing relapse in premenopausal women with early stage ER+
      breast cancer (Klijn et al. 2001).

      The efficacy and safety of ribociclib in combination with letrozole for the treatment of
      postmenopausal women with advanced or metastatic breast cancer vs. placebo (i.e., letrozole
      alone) was already demonstrated in the preceding, pivotal MONALESSA-2 study. Thus, for
      ethical reasons no endocrine comparator drugs were investigated in the present RIBECCA study.

      Generally, the single-arm, open-label design and the broadening of the study population
      (compared to the pivotal MONALESSA-2 study) in the RIBECCA study was deemed appropriate to
      further evaluate the efficacy and safety of ribociclib plus letrozole among breast cancer
      patients in a treatment setting closer to routine care. The duration of study treatment of up
      to 80 weeks was considered adequate to determine the primary, secondary and exploratory study
      parameters. Moreover, the sample size was suitable to estimate the CBR in this patient
      population with reasonable precision.

Trial Arms

NameTypeDescriptionInterventions
ribociclib + letrozole cohort AExperimentalribociclib + letrozole cohort A - postmenopausal women, or men; naïve. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.
  • ribociclib
  • letrozole
  • goserelin
ribociclib + letrozole cohort B1Experimentalribociclib + letrozole cohort B1 - premenopausal women or perimenopausal women; naïve All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly
  • ribociclib
  • letrozole
  • goserelin
ribociclib + letrozole cohort B2Experimentalribociclib + letrozole cohort B2 - premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated. All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly
  • ribociclib
  • letrozole
  • goserelin

Eligibility Criteria

        Inclusion Criteria:

          -  Patient is an adult, ≥ 18 years old at the time of informed consent and has signed
             informed consent before any trial related activities and according to local guidelines

          -  Women and men with advanced (locoregionally recurrent or metastatic) breast cancer not
             amenable to curative therapy.

          -  Patient has a histologically and/or cytologically confirmed diagnosis of
             estrogen-receptor positive and/or progesterone receptor positive and HER2-negative
             breast cancer by local laboratory. Local pathology is sufficient for assessment.

          -  Patient must have either:

               1. Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1
                  criteria ).

               2. Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable
                  disease

               3. Non-measurable disease

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2

        Exclusion Criteria

          -  Patient who received any CDK4/6 inhibitor or any mTOR inhibitor.

          -  Patient has a known hypersensitivity to any of the excipients of ribociclib or
             letrozole

          -  Patients with current inflammatory breast cancer.

          -  Patient has received > 1 chemotherapy for the treatment of advanced/metastatic breast
             cancer

          -  Patient has received > 2 endocrine therapies for the treatment of advanced/metastatic
             breast cancer

          -  Patient has central nervous system (CNS) involvement. If patient is fulfilling the
             following 3 criteria she/he is eligible for the trial.

               1. completed prior therapy (including radiation and/or surgery) for CNS metastases ≥
                  28 days prior to the start of study and

               2. CNS tumor is clinically stable at the time of screening and

               3. Patient is not receiving steroids and enzyme inducing anti-epileptic medications
                  for brain metastases

          -  Patient has active cardiac disease or a history of cardiac dysfunction
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole
Time Frame:At 24 weeks after last patient enrolled in trial
Safety Issue:
Description:Clinical Benefit Rate (CBR) after 24 weeks of treatment as defined by RECIST 1.1 as percentage of patients with Complete Response (CR), Partial response (PR) or Stable disease (SD) lasting 24 weeks or longer as well as patients with Non-complete response, nonprogressive disease (NCRNPD).

Secondary Outcome Measures

Measure:Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI)
Time Frame:At week 24 , week 48 and week 72
Safety Issue:
Description:PFS based on radiologic assessment by investigator using RECIST 1.1 criteria
Measure:Progression Free Survival (PFS) for Different Populations - Median Time to Progression or Death With 95% CI [Months]
Time Frame:Up to approximately month 25
Safety Issue:
Description:PFS based on radiologic assessment by investigator using RECIST 1.1 criteria
Measure:Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI)
Time Frame:At Week 24, Week 48 and Week 72
Safety Issue:
Description:Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause. For the Kaplan-Meier estimates (%, 95% CI), the probability of survival at week 24, 48 and 72 is reported below.
Measure:Overall Survival (OS) - Median Time to Progression or Death With 95% CI [Months]
Time Frame:Up to approximatley 38 months
Safety Issue:
Description:Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause.
Measure:Overall Survival (OS) - Number of Censored Participants and Number of Deaths
Time Frame:Up to approximatley 38 months
Safety Issue:
Description:Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause.
Measure:Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI)
Time Frame:At week 24
Safety Issue:
Description:Overall response rate (ORR) is the best overall response (BOR) of complete response (CR) or partial response (PR) as defined by RECIST 1.1.
Measure:Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30
Time Frame:Change from Baseline to Week 24
Safety Issue:
Description:The QLQ-C30 is the core questionnaire of the EORTC QLQ, which has been developed for the assessment of the health-related QOL of cancer patients participating in international clinical trials. Using a linear transformation to standardize the raw scores, all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher ("better") level of functioning (applies to the first 6 items, items 1 to 6), but a higher ("worse") level of symptoms (applies to the last 9 items, items 7 to 15). There is no aggregated total score, i.e., all scale scores were analyzed separately.
Measure:Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7)
Time Frame:Baseline and Week 24 (Cycle 7)
Safety Issue:
Description:To evaluate health related quality of life (QoL) via EORTC BR-23. The scoring approach for the QLQ-BR23 is identical in principle to that for the function and symptom scales / single items of the QLQ-C30, i.e., all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher ("better") level of functioning, (applies to the first 4 items, items 1 to 4) but a higher ("worse") level of symptoms (applies to the last 4 items, items 5 to 8).
Measure:Time to 10% Deterioration in EORTC Global Health Status
Time Frame:up to approximately 10 months
Safety Issue:
Description:Time to 10% deterioration in the European Organisation for Research and Treatment of Cancer (EORTC) global health status
Measure:Number of Participants With Treatment Emergent Adverse Events (TEAE)
Time Frame:Up to Week 72
Safety Issue:
Description:Adverse Events (AEs) were separated into TEAEs (defined as AEs occurring/worsening from first study drug treatment until 30 days after the last study drug treatment) and AEs in the pre-/post-treatment period.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • ribociclib
  • LEE011
  • RIBECCA
  • breast cancer
  • breast carcinoma
  • HR-positive
  • HER2-negative
  • advanced breast cancer
  • Letrozole
  • CDK4/6
  • breast lump
  • HER2 positive
  • metastatic breast cancer
  • breast cancer positive for human epidermal growth factor receptor 2 (HER2) HER2 positive metastatic breast cancer
  • breast cancer progression
  • estrogen-receptor (ER) positive(+) breast cancer
  • Paget's disease

Last Updated

May 19, 2021