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Breast CancerPhase 3RIBBITNCT03462251

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

A Phase 3 study testing Ribociclib and aromatase inhibitor or fulvestrant and Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab in people with Breast Cancer and Hormone Receptor Positive Tumor, run by iOMEDICO AG at 27 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Ribociclib and aromatase inhibitor or fulvestrant and Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
27 sitesGermany
Study dates
24 May 2018to 30 Nov 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

Germany27 sites

  • Uniklinik RWTH Aachen, Gynäkologie und Geburtsmedizin

    Aachen, 52074

  • Klinikum Mittelbaden Baden-Baden Balg

    Baden-Baden, 76532

  • Gynäkologisches Zentrum Bonn

    Bonn, 53111

  • St.-Johannes-Hospital Gynäkologie und Geburtshilfe

    Dortmund, 44137

  • BAG / Onkologische Gemeinschaftspraxis

    Dresden, 01307

  • Universitätsklinikum Essen

    Essen, 45147

  • Praxis für interdisziplinäre Onkologie & Hämatologie

    Freiburg im Breisgau, 79110

  • Überörtliche Berufsausübungsgemeinschaft MVZ Onkologische Kooperation Harz

    Goslar, 38642

  • Gemeinschaftspraxis für Innere Medizin, Hämatologie, Onkologie, Gastroenterologie

    Halle, 06110

  • OncoResearch Lerchenfeld GmbH

    Hamburg, 22081

  • Onkologische Schwerpunktpraxis

    Heidelberg, 69115

  • IDGGQ GbR

    Kaiserslautern, 67655

  • Hämato-Onkologisches Zentrum Kassel MVZ GmbH

    Kassel, 34119

  • Praxis Dr. med. Bettina Peuser

    Leipzig, 04179

  • Gemeinschaftspraxis für Hämatologie und Onkologie

    Mühlheim, 45468

  • Hämatologisch-onkologische Gemeinschaftspraxis

    Münster, 48149

  • Praxis Dr. med. Jens Uhlig

    Naunhof, 04683

  • Klinikum Neumarkt

    Neumarkt, 92318

  • Onkologie Offenburg

    Offenburg, 77654

  • Gemeinschaftspraxis für Hämatologie und Onkologie

    Ravensburg, Baden-Wurttemberg, 88212

  • Praxis und Tagesklinik für Onkologie und Hämatologie

    Recklinghausen, 45659

  • Tumorzentrum und Hausarztpraxis Rötha Leipziger-Land

    Rötha, 04571

  • Schwerpunktpraxis für Hämatologie und Internistische Onkologie, Gastroenterologie

    Singen, 78224

  • Onkologische Schwerpunktpraxis

    Speyer, 67346

  • g.SUND Gynäkologie Kompetenzzentrum Stralsund

    Stralsund, 18435

  • Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

    Villingen-Schwenningen, 78052

  • Gemeinschaftspraxis für Hämatologie und Onkologie

    Westerstede, 26655

Other trials in Germany

About this study

Official title: 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

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.

Read the 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.

Being tested
Ribociclib and aromatase inhibitor or fulvestrant, Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab
Keywords
Breast Cancer, HR positive, HER2 negative, Mamma carcinoma
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ribociclib and aromatase inhibitor or fulvestrantCombination product

    Combination of ribociclib and aromatase inhibitor or fulvestrant

  • Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumabCombination product

    Capecitabine with bevacizumab OR Paclitaxel with or without bevacizumab

Study groups in NCT03462251
Study groupRoleWhat they receive
Arm AExperimentalCombination of ribociclib and aromatase inhibitor or fulvestrant
Receives: Combination Product: Ribociclib and aromatase inhibitor or fulvestrant
Arm BActive comparatorCapecitabine + bevacizumab OR Paclitaxel +/- bevacizumab
Receives: Combination Product: Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to approximately 15 months.

Secondary outcomes (11)

  1. Overall Survival (OS)

    OS is defined as time from randomization to death of any cause.

    Measured: Up to approximately 48 months.

  2. Overall Response Rate (ORR)

    ORR is defined as the proportion of patients with best overall response of complete or partial response according to RECIST 1.1.

    Measured: Up to approximately 15 months.

  3. Clinical Benefit Rate (CBR)

    CBR is defined as the proportion of patients with best overall response of complete or partial response or stable disease lasting 24 weeks or more according to RECIST 1.1.

    Measured: Up to approximately 15 months

  4. Time To Response (TTR)

    TTR is defined as time from randomization to first occurrence of any response (complete or partial) according to RECIST 1.1.

    Measured: Up to approximately 15 months.

  5. Number of participants with Adverse Events

    Type, frequency and severity (according to CTCAE v4.03) of adverse events

    Measured: Until 30 days after end of treatment, up to approximately 16 months.

  6. Time to deterioration of ECOG performance status

    Time to deterioration of ECOG performance status by at least one point from baseline.

    Measured: Until 30 days after end of treatment, up to approximately 16 months

  7. Tolerability of treatment

    By-patient listings of safety laboratory (hemoglobin, platelets, white blood cells with differentials, international normalized ratio , serum creatinine, bilirubin, Alanine-Aminotransferase (ALT) and Aspartate-Aminotransferase (AST)).

    Measured: Until 30 days after end of treatment, up to approximately 16 months.

  8. corrected QT interval (QTc) time

    By-patient listings of cardiac monitoring.

    Measured: Until 30 days after end of treatment, up to approximately 16 months.

  9. Health-related quality of life (QoL)

    Health-related QoL will be assessed with the EORTC Quality of life questionnaire (QLQ) QLQ-C30.

    Measured: Up to 36 months.

  10. Side effects of treatment

    One question on treatment burden

    Measured: Up to 36 months.

  11. Time spent on treatment

    Burden by treatment will be assessed with 4 questions on time spent on treatment

    Measured: Up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2018
  2. Study start24 May 2018
  3. Primary completion30 Nov 2021
  4. Study completion30 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03462251
Sponsor's protocol ID
IOM-050371
Acronym
RIBBIT
Status last verified
Jan 2023
First submitted
16 Feb 2018
Last updated
19 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ribociclib and aromatase inhibitor or fulvestrant and Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab in people with Breast Cancer and Hormone Receptor Positive Tumor, run by iOMEDICO AG at 27 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy in terms of PFS (time frame: Up to approximately 15 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03462251.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2023.

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