Clinical Trials /

Anti-hormonal Therapie With or Without Ribociclib in HR-positive / HER2- Negative Metastatic Breast Cancer

NCT03555877

Description:

This is a multicenter, prospective, randomized, open-label, controlled phase II study to test the addition of the CDK4/6 inhibitor ribociclib to anti-hormonal treatment as maintenance therapy in patients with disease control (at least stable disease) after 1st line chemotherapy.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Anti-hormonal Therapie With or Without Ribociclib in HR-positive / HER2- Negative Metastatic Breast Cancer
  • Official Title: Anti-hormonal Maintenance Treatment With or Without the CDK4/6 Inhibitor Ribociclib After 1st Line Chemotherapy in Hormone Receptor Positive / HER2 Negative Metastatic Breast Cancer: A Phase II Trial

Clinical Trial IDs

  • ORG STUDY ID: GBG 97
  • NCT ID: NCT03555877

Conditions

  • Breast Cancer Metastatic

Interventions

DrugSynonymsArms
RibociclibKisqaliAnti-hormonal treatment + ribociclib
AnastrozoleAll marketed medicinal products with this active ingredient.Anti-hormonal treatment + ribociclib
LetrozoleAll marketed medicinal products with this active ingredient.Anti-hormonal treatment + ribociclib
ExemestaneAll marketed medicinal products with this active ingredient.Anti-hormonal treatment + ribociclib
FulvestrantAll marketed medicinal products with this active ingredient.Anti-hormonal treatment + ribociclib
TamoxifenAll marketed medicinal products with this active ingredient.Anti-hormonal treatment + ribociclib

Purpose

This is a multicenter, prospective, randomized, open-label, controlled phase II study to test the addition of the CDK4/6 inhibitor ribociclib to anti-hormonal treatment as maintenance therapy in patients with disease control (at least stable disease) after 1st line chemotherapy.

Detailed Description

      Although 1st line chemotherapy is effective in women with HR-positive HER2-negative breast
      cancer, PFS is usually around 6-8 months and 2nd or 3rd line treatments are by far less
      effective. Well tolerated maintenance treatments with the potential to prolong PFS and even
      OS are urgently needed. This study evaluates the impact of the addition of a CDK4/6 inhibitor
      to an anti-hormonal maintenance treatment of physicians´ choice.
    

Trial Arms

NameTypeDescriptionInterventions
Anti-hormonal treatment + ribociclibExperimentalIn the experimental arm ribociclib will be dosed on a flat scale of 600mg/day (corresponding to three 200mg tablets once daily, 3 week on, one week off). Anti-hormonal/endocrine treatment of choice of investigator: anastrozole, exemestane, letrozole, fulvestrant, tamoxifen.
  • Ribociclib
  • Anastrozole
  • Letrozole
  • Exemestane
  • Fulvestrant
  • Tamoxifen
Anti-hormonal treatmentActive ComparatorIn the control arm patients will receive endocrine treatment only (of choise of investigator). Anti-hormonal/endocrine treatment of choice of investigator: anastrozole, exemestane, letrozole, fulvestrant, tamoxifen.
  • Anastrozole
  • Letrozole
  • Exemestane
  • Fulvestrant
  • Tamoxifen

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent prior to beginning specific protocol procedures, including
             expected cooperation of the patients for the treatment and follow-up, must be obtained
             and documented according to the local regulatory requirements.

          2. Female patients.

          3. Age ≥ 18 years old.

          4. Histologically confirmed HER2-/HR+ locally advanced or metastatic invasive breast
             carcinoma assessed on the primary tumor and/or on the metastatic lesions (preferred).

          5. Willingness and ability to provide archived formalin fixed paraffin embedded tissue
             block or a partial block from primary surgery and/or tumor or metastasis biopsy, which
             will be used for further breast cancer research.

          6. Maintenance endocrine therapy could have already been started up to 6 weeks before
             randomization, but after achievement of tumor response or stable disease.

          7. Maintenance therapy must be preceded prior to randomization by at least 4 cycles of a
             mono- or polychemotherapy. Tumor response or stable disease needs to be maintained to
             allow entry into the trial. Study treatment must start within 8 weeks of the last dose
             of chemotherapy.

          8. Previous therapy with maximum one line of anti-hormonal treatment is allowed.

          9. Previous neoadjuvant/adjuvant therapy is allowed. In case of cancer other than breast
             cancer, treatment should be completed more than 5 years before study entry.

         10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

         11. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical
             procedures to NCI CTCAE version 4.03 Grade ≤ 1 (except alopecia or other toxicities
             not considered a safety risk for the patient at investigator's discretion).

         12. The patient must be accessible for scheduled visits, treatment and follow-up. Patients
             registered on this trial must be treated at the participating center which could be
             the Principal or a Co- investigator's site.

         13. Life-expectancy > 6 months.

         14. The subjects need to be either A) of non-childbearing potential (documented
             postmenopausal or post hysterectomy) or B) childbearing potential with negative
             urinary pregnancy test (in this case patients need to use highly effective
             non-hormonal contraceptive).

        Exclusion Criteria:

          1. Uncontrolled/untreated central nervous system lesions.

          2. Subjects who had previously received a CDK4/6 inhibitor.

          3. Known severe hypersensitivity reactions to compounds similar to one of the
             investigational (active substance or peanut, soya or other excipients) and supportive
             treatment.

          4. Inadequate organ function immediate prior to randomization including:

               -  Hemoglobin < 10 g/dL

               -  Absolute neutrophil count (ANC) < 2000/mm³ (< 2.0 x 109/L)

               -  Platelets < 100,000/mm³ (< 100 x 109/L)

               -  Alanine aminotransferase (ALAT/SGPT) and/or aspartate aminotransferase
                  (ASAT/SGOT) > 2.0 x upper normal limits (ULN). If the patient has liver
                  metastases, ALT and AST should not be ≥5 ULN.

               -  Alkaline phosphatase (ALP) > 2.5 x ULN

               -  Total serum bilirubin > 1.5 x ULN

               -  Serum creatinine >1.5 x ULN or estimated creatinine clearance < 60 mL/min as
                  calculated using the method standard for the Institution

          5. Severe and relevant comorbidity that would interact with the participation in the
             study.

          6. Previous malignant disease being disease-free for less than 5 years (except CIS of the
             cervix and non-melanomatous skin cancer).

          7. Evidence for active infection including wound infections and anamnestic HIV or
             hepatitis.

          8. QTc >450 msec or a family or personal history of long or short QT syndrome, Brugada
             syndrome or known history of QTc prolongation, or Torsade de Pointes.

          9. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging
             drug (i.e. hypocalcemia, hypokalemia, hypomagnesemia).

         10. Any of the following within 6 months prior to randomization: myocardial infarction,
             severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.03 grade ≥
             2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft,
             symptomatic congestive heart failure, cerebrovascular accident including transient
             ischemic attack, or symptomatic pulmonary embolism.

         11. Other severe acute, uncontrolled or chronic medical or psychiatric condition or
             laboratory abnormality that may increase the risk associated with study participation
             or investigational product administration or may interfere with the interpretation of
             study results and, in the judgment of the investigator, would make the patient
             inappropriate for entry into this study.

         12. Concurrent treatment with other experimental drugs. Participation in another clinical
             trial with any investigational not marketed drug within 30 days prior to study entry.

         13. Patients treated within the last 7 days prior to randomization with drugs known to be
             CYP3A4 inhibitors or inducers (see section 11.4) or drugs that are known to prolong
             the QT interval.

         14. Pregnant and lactating women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Locally-assessed progression-free survival (PFS)
Time Frame:Up to 21 months
Safety Issue:
Description:Primary efficacy endpoint is locally-assessed progression-free survival (PFS) defined as the time elapsed between randomization and tumor progression or death from any cause.

Secondary Outcome Measures

Measure:The impact on overall survival
Time Frame:Up to 21 months
Safety Issue:
Description:Overall survival (OS) defined as the time elapsed between treatment randomization and death from any cause
Measure:The clinical benefit rate
Time Frame:Up to 21 months
Safety Issue:
Description:Clinical benefit rate (CBR) defined as the proportion of subjects with best response of complete response, partial response, or stable disease for at least 24 weeks
Measure:Patient reported outcomes
Time Frame:Up to 21 months
Safety Issue:
Description:will be assessed using the General Quality of Life questionnaire (FACT-B), which will be filled in at study entry and every three month thereafter.
Measure:Number of participants with adverse events, serious adverse events and adverse events of special interest as assessed by CTCAE v4.03.
Time Frame:Up to 15 months
Safety Issue:
Description:Number of participants with adverse events, serious adverse events and adverse events of special interest as assessed by CTCAE v4.03 compared between the two treatment-arms.
Measure:The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that.
Time Frame:Up to 15 months
Safety Issue:
Description:The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that compared between two treatment-arms.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:German Breast Group

Trial Keywords

  • Ribociclib
  • Anti-hormonal maintainance treatment
  • HR-positive
  • HER2-negative

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