Ribociclib and Endocrine Therapy or Chemotherapy With or Without Bevacizumab for Metastatic Breast Cancer in First Line

NCT ID: NCT03462251

Last Updated: 2023-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-24
• Study Completion Date: 2022-11-30

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.

Conditions

Breast Cancer; Hormone Receptor Positive Tumor; HER 2 Negative Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Combination of ribociclib and aromatase inhibitor or fulvestrant

Group Type: EXPERIMENTAL

Ribociclib and aromatase inhibitor or fulvestrant

Intervention Type: COMBINATION_PRODUCT

Combination of ribociclib and aromatase inhibitor or fulvestrant

Arm B

Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab

Group Type: ACTIVE_COMPARATOR

Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab

Intervention Type: COMBINATION_PRODUCT

Capecitabine with bevacizumab OR Paclitaxel with or without bevacizumab

Interventions

Ribociclib and aromatase inhibitor or fulvestrant

Combination of ribociclib and aromatase inhibitor or fulvestrant

Intervention Type: COMBINATION_PRODUCT

Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab

Capecitabine with bevacizumab OR Paclitaxel with or without bevacizumab

Intervention Type: COMBINATION_PRODUCT

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 0-1.
• Adequate organ and bone marrow function within 7 days prior to randomization.
• Standard 12-lead ECG values: QT Interval Corrected by the Fridericia Correction Formula (QTcF) interval at screening < 450 msec; Mean resting heart rate 50-90 bpm (determined from the ECG)
• Signed written informed consent prior to beginning of protocol-specific procedures.

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-35.
• 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)
• Patient with congenital bleeding diathesis, acquired coagulopathy or under full dose of anticoagulants.
• Patient is currently receiving strong inducers or inhibitors of CYP3A4/5 or medication with narrow therapeutic window that are predominantly metabolized through CYP3A4/5 and cannot be discontinued 7 days prior to start of study treatment.
• Known presence of cerebral metastases unless at least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment and clinically stable central nervous system tumor at the time of screening.
• Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
• Patient is currently receiving or has received systemic corticosteroids or other chronic immunosuppressive therapy ≤ 2 weeks prior to starting study drug.
• Patients with advanced symptomatic, visceral spread, that are at risk of lifethreatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
• Patient has a known history of HIV infection (testing not mandatory).
• Patient has active untreated or uncontrolled fungal, bacterial or viral infection.
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, etc.).
• Participation in prior investigational studies within 30 days prior to randomization or within 5-half lives of the investigational product, whichever is longer.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

iOMEDICO AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Decker, Prof.

Role: PRINCIPAL_INVESTIGATOR

Gemeinschaftspraxis für Hämatologie und Onkologie

Locations

Gemeinschaftspraxis für Hämatologie und Onkologie

Ravensburg, Baden-Wurttemberg, Germany

Uniklinik RWTH Aachen, Gynäkologie und Geburtsmedizin

Aachen, , Germany

Klinikum Mittelbaden Baden-Baden Balg

Baden-Baden, , Germany

Gynäkologisches Zentrum Bonn

Bonn, , Germany

St.-Johannes-Hospital Gynäkologie und Geburtshilfe

Dortmund, , Germany

BAG / Onkologische Gemeinschaftspraxis

Dresden, , Germany

Universitätsklinikum Essen

Essen, , Germany

Praxis für interdisziplinäre Onkologie & Hämatologie

Freiburg im Breisgau, , Germany

Überörtliche Berufsausübungsgemeinschaft MVZ Onkologische Kooperation Harz

Goslar, , Germany

Gemeinschaftspraxis für Innere Medizin, Hämatologie, Onkologie, Gastroenterologie

Halle, , Germany

OncoResearch Lerchenfeld GmbH

Hamburg, , Germany

Onkologische Schwerpunktpraxis

Heidelberg, , Germany

IDGGQ GbR

Kaiserslautern, , Germany

Hämato-Onkologisches Zentrum Kassel MVZ GmbH

Kassel, , Germany

Praxis Dr. med. Bettina Peuser

Leipzig, , Germany

Gemeinschaftspraxis für Hämatologie und Onkologie

Mühlheim, , Germany

Hämatologisch-onkologische Gemeinschaftspraxis

Münster, , Germany

Praxis Dr. med. Jens Uhlig

Naunhof, , Germany

Klinikum Neumarkt

Neumarkt, , Germany

Onkologie Offenburg

Offenburg, , Germany

Praxis und Tagesklinik für Onkologie und Hämatologie

Recklinghausen, , Germany

Tumorzentrum und Hausarztpraxis Rötha Leipziger-Land

Rötha, , Germany

Schwerpunktpraxis für Hämatologie und Internistische Onkologie, Gastroenterologie

Singen, , Germany

Onkologische Schwerpunktpraxis

Speyer, , Germany

g.SUND Gynäkologie Kompetenzzentrum Stralsund

Stralsund, , Germany

Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

Villingen-Schwenningen, , Germany

Gemeinschaftspraxis für Hämatologie und Onkologie

Westerstede, , Germany

Countries

Germany

Other Identifiers

IOM-050371

Identifier Type: -

Identifier Source: org_study_id