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.
Title
- Brief Title: Anti-hormonal Therapie With Ribociclib in HR-positive / HER2- Negative Metastatic Breast Cancer
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
GBG 97
- NCT ID:
NCT03555877
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Ribociclib | Kisqali | Anti-hormonal treatment + ribociclib |
Anastrozole | All marketed medicinal products with this active ingredient. | Anti-hormonal treatment |
Letrozole | All marketed medicinal products with this active ingredient. | Anti-hormonal treatment |
Exemestane | All marketed medicinal products with this active ingredient. | Anti-hormonal treatment |
Fulvestrant | All marketed medicinal products with this active ingredient. | Anti-hormonal treatment |
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
Name | Type | Description | Interventions |
---|
Anti-hormonal treatment + ribociclib | Experimental | 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. | - Ribociclib
- Anastrozole
- Letrozole
- Exemestane
- Fulvestrant
|
Anti-hormonal treatment | Active Comparator | 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. | - Anastrozole
- Letrozole
- Exemestane
- Fulvestrant
|
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. 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.
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 39 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 39 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 39 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 39 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 33 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 33 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
Last Updated
February 3, 2021