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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03555877
Recruitment Status : Unknown
Verified June 2018 by German Breast Group.
Recruitment status was:  Recruiting
First Posted : June 14, 2018
Last Update Posted : June 14, 2018
Sponsor:
Information provided by (Responsible Party):
German Breast Group

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Metastatic Drug: Ribociclib Drug: Anastrozole Drug: Letrozole Drug: Exemestane Drug: Fulvestrant Drug: Tamoxifen Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 15, 2018
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Ribociclib

Arm Intervention/treatment
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, tamoxifen.
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.

Drug: Tamoxifen
20mg once daily as indicated in the SmPC
Other Name: All marketed medicinal products with this active ingredient.

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, tamoxifen.
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.

Drug: Tamoxifen
20mg once daily as indicated in the SmPC
Other Name: All marketed medicinal products with this active ingredient.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03555877


Contacts
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Contact: Viktoria Tierbach +49 (0) 1602 7480 ext 238 amica@gbg.de

Locations
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Germany
Studienzentrum Onkologie Ravensburg Recruiting
Ravensburg, Germany, 88212
Contact: Thomas Decker, Prof. Dr.    +49 (0) 7513661970 ext 0    thomas.decker@onkonet.eu   
Sponsors and Collaborators
German Breast Group
Investigators
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Principal Investigator: Thomas Decker, Prof. Dr. Gemeinschaftspraxis Onkologie Ravensburg
Additional Information:
Publications:
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Responsible Party: German Breast Group
ClinicalTrials.gov Identifier: NCT03555877    
Other Study ID Numbers: GBG 97
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by German Breast Group:
Ribociclib
Anti-hormonal maintainance treatment
HR-positive
HER2-negative
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Letrozole
Fulvestrant
Anastrozole
Exemestane
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Estrogen Receptor Antagonists