A Randomized, Open-label, Multicenter, Two-arm, Phase III Study to Evaluate Efficacy and Quality of Life in Patients With Metastatic Hormone Receptor-positive HER2-negative Breast Cancer Receiving Ribociclib in Combination With Endocrine Therapy or Chemotherapy With or Without Bevacizumab in First Line
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Breast Cancer
- Sponsor
- iOMEDICO AG
- Enrollment
- 41
- Locations
- 24
- Primary Endpoint
- Efficacy in terms of PFS
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This study is designed to evaluate the efficacy and safety of first-line treatment ribociclib in combination with aromatase inhibitor (AI) or fulvestrant OR capecitabine with bevacizumab OR paclitaxel with / without bevacizumab in patients with HR-positive, HER2-negative advanced breast cancer with visceral metastasis.
Half of the patients will receive a combination of ribociclib and AI/fulvestrant while the other half will receive capecitabine + bevacizumab or paclitaxel +/- bevacizumab.
Detailed Description
This is a prospective, randomized, open-label, two-arm, multicenter, interventional phase III trial in Germany. The study will include adult women with HR-positive, HER2-negative advanced breast cancer with visceral metastases, who received no prior therapy for advanced disease. 158 patients will be enrolled and randomized 1:1 (stratified by the presence of lung and / or liver metastases) to receive Arm A: a combination of ribociclib and AI or fulvestrant; OR Arm B: capecitabine + bevacizumab OR paclitaxel +/- bevacizumab Treatment will be continued until disease progression, intolerable toxicity or death. Progression-free survival (PFS) will be based on tumor assessments by local radiologists/investigator using RECIST v1.1 criteria. Treatment might be continued beyond RECIST-defined progressive disease (PD) in case of negligible or clinically irrelevant disease progression according to the investigator's discretion until clinically relevant disease progression or symptomatic deterioration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years.
- •Any menopausal status. If pre-/perimenopausal, agreement to receive LHRH agonist (goserelin or leuprorelin) / ovarian ablation in case of randomization to arm A
- •Locally confirmed diagnosis of metastatic adenocarcinoma of the breast without prior systemic antineoplastic therapy in the palliative setting.
- •Hormone receptor (HR)-positive disease, defined as estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive.
- •Human epidermal growth factor receptor 2 (HER2)-negative disease (defined as immunohistochemistry (IHC) status HER2 negative/+ or IHC HER2++ with chromosomal in situ hybridization (CISH)/fluorescent in situ hybridization (FISH) negative).
- •Presence of visceral metastases (additional non-visceral metastases are allowed).
- •Presence of target and / or non-target lesions according to RECIST v1.1
- •Patients eligible for palliative treatment with AI / fulvestrant + ribociclib and capecitabine + bevacizumab or paclitaxel + / - bevacizumab according to the respective SmPCs.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Adequate organ and bone marrow function within 7 days prior to randomization.
Exclusion Criteria
- •Any prior systemic palliative therapy
- •Prior treatment with any cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.
- •Prior adjuvant or neoadjuvant taxane therapy if last application within 12 months prior to entering the study.
- •Patient is concurrently using other anti-cancer therapy.
- •Patient has had major surgery within 28 days prior to randomization or has not recovered from major side effects or wound is not fully recovered.
- •Patient has received extended-field radiotherapy ≤ 4 weeks or limited-field radiotherapy ≤ 2 weeks prior to randomization.
- •Known hypersensitivity to ribociclib, AI, paclitaxel, bevacizumab or any of their excipients, or against peanut, soya, Chinese hamster ovarian cell products or macrogolglycerol ricinoleate-
- •Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality (e.g. history of myocardial infarction within 6 months prior study entry, long QT syndrome, clinically significant cardiac arrhythmias or systolic blood pressure \> 140 or \< 90 mmHg or diastolic blood pressure \> 90 mmHg).
- •Patient has history of arterial thrombosis within 12 months prior to entering the study.
- •Patient has proteinuria (≥ 2+ on urine dipstick)
Outcomes
Primary Outcomes
Efficacy in terms of PFS
Time Frame: Up to approximately 15 months.
PFS is defined as time from randomization to progression of disease or death of any cause, whichever comes first. It will be assessed by imaging until progressive disease or start of next-line therapy.
Secondary Outcomes
- Overall Survival (OS)(Up to approximately 48 months.)
- corrected QT interval (QTc) time(Until 30 days after end of treatment, up to approximately 16 months.)
- Tolerability of treatment(Until 30 days after end of treatment, up to approximately 16 months.)
- Time To Response (TTR)(Up to approximately 15 months.)
- Number of participants with Adverse Events(Until 30 days after end of treatment, up to approximately 16 months.)
- Overall Response Rate (ORR)(Up to approximately 15 months.)
- Clinical Benefit Rate (CBR)(Up to approximately 15 months)
- Side effects of treatment(Up to 36 months.)
- Time to deterioration of ECOG performance status(Until 30 days after end of treatment, up to approximately 16 months)
- Time spent on treatment(Up to 36 months)
- Health-related quality of life (QoL)(Up to 36 months.)