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

NCT03462251 | Completed Phase 3

• 1 other identifier: IOM-050371
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 27

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.

Conditions

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

Keywords

Breast Cancer; HR positive; HER2 negative; Mamma carcinoma

Outcome Measures

Primary Outcomes (1)

• Efficacy in terms of PFS

  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.

  Up to approximately 15 months.

Secondary Outcomes (11)

• Overall Survival (OS)

  Up to approximately 48 months.

• Overall Response Rate (ORR)

  Up to approximately 15 months.

• Clinical Benefit Rate (CBR)

  Up to approximately 15 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.

Other Outcomes (1)

• Symptomatic PFS (sPFS)

  Up to approximately 15 months.

Study Arms (2)

Arm A

EXPERIMENTAL

Combination of ribociclib and aromatase inhibitor or fulvestrant

Combination Product: Ribociclib and aromatase inhibitor or fulvestrant

Arm B

ACTIVE COMPARATOR

Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab

Combination Product: Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab

Interventions

Ribociclib and aromatase inhibitor or fulvestrant COMBINATION_PRODUCT

Combination of ribociclib and aromatase inhibitor or fulvestrant

Arm A

Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab COMBINATION_PRODUCT

Capecitabine with bevacizumab OR Paclitaxel with or without bevacizumab

Arm B

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: women (any menopausal status)
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• iOMEDICO AG: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (27)

Gemeinschaftspraxis für Hämatologie und Onkologie

Ravensburg, Baden-Wurttemberg, 88212, Germany

Location

Uniklinik RWTH Aachen, Gynäkologie und Geburtsmedizin

Aachen, 52074, Germany

Location

Klinikum Mittelbaden Baden-Baden Balg

Baden-Baden, 76532, Germany

Location

Gynäkologisches Zentrum Bonn

Bonn, 53111, Germany

Location

St.-Johannes-Hospital Gynäkologie und Geburtshilfe

Dortmund, 44137, Germany

Location

BAG / Onkologische Gemeinschaftspraxis

Dresden, 01307, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Praxis für interdisziplinäre Onkologie & Hämatologie

Freiburg im Breisgau, 79110, Germany

Location

Überörtliche Berufsausübungsgemeinschaft MVZ Onkologische Kooperation Harz

Goslar, 38642, Germany

Location

Gemeinschaftspraxis für Innere Medizin, Hämatologie, Onkologie, Gastroenterologie

Halle, 06110, Germany

Location

OncoResearch Lerchenfeld GmbH

Hamburg, 22081, Germany

Location

Onkologische Schwerpunktpraxis

Heidelberg, 69115, Germany

Location

IDGGQ GbR

Kaiserslautern, 67655, Germany

Location

Hämato-Onkologisches Zentrum Kassel MVZ GmbH

Kassel, 34119, Germany

Location

Praxis Dr. med. Bettina Peuser

Leipzig, 04179, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie

Mühlheim, 45468, Germany

Location

Hämatologisch-onkologische Gemeinschaftspraxis

Münster, 48149, Germany

Location

Praxis Dr. med. Jens Uhlig

Naunhof, 04683, Germany

Location

Klinikum Neumarkt

Neumarkt, 92318, Germany

Location

Onkologie Offenburg

Offenburg, 77654, Germany

Location

Praxis und Tagesklinik für Onkologie und Hämatologie

Recklinghausen, 45659, Germany

Location

Tumorzentrum und Hausarztpraxis Rötha Leipziger-Land

Rötha, 04571, Germany

Location

Schwerpunktpraxis für Hämatologie und Internistische Onkologie, Gastroenterologie

Singen, 78224, Germany

Location

Onkologische Schwerpunktpraxis

Speyer, 67346, Germany

Location

g.SUND Gynäkologie Kompetenzzentrum Stralsund

Stralsund, 18435, Germany

Location

Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

Villingen-Schwenningen, 78052, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie

Westerstede, 26655, Germany

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; Aromatase Inhibitors; Fulvestrant; Capecitabine; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Thomas Decker, Prof.

  Gemeinschaftspraxis für Hämatologie und Onkologie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2018
• First Posted: March 12, 2018
• Study Start: May 24, 2018
• Primary Completion: November 30, 2021
• Study Completion: November 30, 2022
• Last Updated: January 19, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (27)