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Anti-hormonal Therapie With Ribociclib in HR-positive / HER2- Negative Metastatic Breast Cancer (AMICA)

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ClinicalTrials.gov Identifier: NCT03555877
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : February 3, 2021
Sponsor:
Information provided by (Responsible Party):
German Breast Group

Tracking Information
First Submitted Date  ICMJE February 16, 2018
First Posted Date  ICMJE June 14, 2018
Last Update Posted Date February 3, 2021
Actual Study Start Date  ICMJE March 15, 2018
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2021)
Locally-assessed progression-free survival (PFS) [ Time Frame: Up to 39 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 1, 2018)
Locally-assessed progression-free survival (PFS) [ Time Frame: Up to 21 months ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2021)
  • The impact on overall survival [ Time Frame: Up to 39 months ]
    Overall survival (OS) defined as the time elapsed between treatment randomization and death from any cause
  • The clinical benefit rate [ Time Frame: Up to 39 months ]
    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
  • Patient reported outcomes [ Time Frame: Up to 39 months ]
    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.
  • 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 33 months ]
    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.
  • The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that. [ Time Frame: Up to 33 months ]
    The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that compared between two treatment-arms.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2018)
  • The impact on overall survival [ Time Frame: Up to 21 months ]
    Overall survival (OS) defined as the time elapsed between treatment randomization and death from any cause
  • The clinical benefit rate [ Time Frame: Up to 21 months ]
    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
  • Patient reported outcomes [ Time Frame: Up to 21 months ]
    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.
  • 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 ]
    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.
  • The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that. [ Time Frame: Up to 15 months ]
    The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that compared between two treatment-arms.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-hormonal Therapie With Ribociclib in HR-positive / HER2- Negative Metastatic Breast Cancer
Official Title  ICMJE Anti-hormonal Maintenance Treatment With the CDK4/6 Inhibitor Ribociclib After 1st Line Chemotherapy in Hormone Receptor Positive / HER2 Negative Metastatic Breast Cancer: A Phase II Trial
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer Metastatic
Intervention  ICMJE
  • Drug: Ribociclib
    Ribociclib in addition to endocrine maintenance therapy. Endocrine therapy, at the discretion of the investigator, could have already been started up to 4 weeks before randomization but not later than with first dose of ribociclib.
    Other Name: Kisqali
  • Drug: Anastrozole
    1mg once daily as indicated in the SmPC
    Other Name: All marketed medicinal products with this active ingredient.
  • Drug: Letrozole
    2,5mg once daily as indicated in the SmPC
    Other Name: All marketed medicinal products with this active ingredient.
  • Drug: Exemestane
    25mg once daily as indicated in the SmPC
    Other Name: All marketed medicinal products with this active ingredient.
  • Drug: Fulvestrant
    (prefilled syringes with fulvestrant 250mg each), 500mg given once a month, with an additional 500mg dose given two weeks after the first dose as indicated in the SmPC
    Other Name: All marketed medicinal products with this active ingredient.
Study Arms  ICMJE
  • Experimental: Anti-hormonal treatment + ribociclib
    In 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.
    Interventions:
    • Drug: Ribociclib
    • Drug: Anastrozole
    • Drug: Letrozole
    • Drug: Exemestane
    • Drug: Fulvestrant
  • Active Comparator: Anti-hormonal treatment
    In 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.
    Interventions:
    • Drug: Anastrozole
    • Drug: Letrozole
    • Drug: Exemestane
    • Drug: Fulvestrant
Publications * Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1351-60. doi: 10.1016/S1470-2045(14)70444-9. Epub 2014 Sep 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 1, 2018)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2022
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Known severe hypersensitivity reactions to compounds similar to one of the investigational (active substance or peanut, soya or other excipients) and supportive treatment.
  3. 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
  4. Severe and relevant comorbidity that would interact with the participation in the study.
  5. Previous malignant disease being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
  6. Evidence for active infection including wound infections and anamnestic HIV or hepatitis.
  7. 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.
  8. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (i.e. hypocalcemia, hypokalemia, hypomagnesemia).
  9. 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.
  10. 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.
  11. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
  12. 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.
  13. Pregnant and lactating women.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Viktoria Tierbach +49 (0) 1602 7480 ext 238 amica@gbg.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03555877
Other Study ID Numbers  ICMJE GBG 97
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party German Breast Group
Study Sponsor  ICMJE German Breast Group
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thomas Decker, Prof. Dr. Gemeinschaftspraxis Onkologie Ravensburg
PRS Account German Breast Group
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP