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

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ClinicalTrials.gov Identifier: NCT03462251
Recruitment Status : Recruiting
First Posted : March 12, 2018
Last Update Posted : July 3, 2019
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
iOMEDICO AG

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Hormone Receptor Positive Tumor HER 2 Negative Breast Cancer Combination Product: Ribociclib and aromatase inhibitor or fulvestrant Combination Product: Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 158 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 24, 2018
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Arm A
Combination of ribociclib and aromatase inhibitor or fulvestrant
Combination Product: Ribociclib and aromatase inhibitor or fulvestrant
Combination of ribociclib and aromatase inhibitor or fulvestrant

Active Comparator: Arm B
Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab
Combination Product: Capecitabine + bevacizumab OR Paclitaxel +/- bevacizumab
Capecitabine with bevacizumab OR Paclitaxel with or without bevacizumab




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 48 months. ]
    OS is defined as time from randomization to death of any cause.

  2. Overall Response Rate (ORR) [ Time Frame: Up to approximately 15 months. ]
    ORR is defined as the proportion of patients with best overall response of complete or partial response according to RECIST 1.1.

  3. Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 15 months ]
    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.

  4. Time To Response (TTR) [ Time Frame: Up to approximately 15 months. ]
    TTR is defined as time from randomization to first occurrence of any response (complete or partial) according to RECIST 1.1.

  5. Number of participants with Adverse Events [ Time Frame: Until 30 days after end of treatment, up to approximately 16 months. ]
    Type, frequency and severity (according to CTCAE v4.03) of adverse events

  6. Time to deterioration of ECOG performance status [ Time Frame: Until 30 days after end of treatment, up to approximately 16 months ]
    Time to deterioration of ECOG performance status by at least one point from baseline.

  7. Tolerability of treatment [ Time Frame: Until 30 days after end of treatment, up to approximately 16 months. ]
    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)).

  8. corrected QT interval (QTc) time [ Time Frame: Until 30 days after end of treatment, up to approximately 16 months. ]
    By-patient listings of cardiac monitoring.

  9. Health-related quality of life (QoL) [ Time Frame: Up to 36 months. ]
    Health-related QoL will be assessed with the EORTC Quality of life questionnaire (QLQ) QLQ-C30.

  10. Side effects of treatment [ Time Frame: Up to 36 months. ]
    One question on treatment burden

  11. Time spent on treatment [ Time Frame: Up to 36 months ]
    Burden by treatment will be assessed with 4 questions on time spent on treatment


Other Outcome Measures:
  1. Symptomatic PFS (sPFS) [ Time Frame: Up to approximately 15 months. ]
    sPFS is defined as time from randomization until symptomatic deterioration (new or worsening of persisting symptoms) or death as per local investigator.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   women (any menopausal status)
Accepts Healthy Volunteers:   No
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 endocrine therapy if last intake within 12 months prior to entering the study.
  • Prior adjuvant or neoadjuvant taxane, anthracycline or fluoropyrimidine 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03462251


Contacts
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Contact: Beate Niemeier, PhD +49 761 15242 ext 13 beate.niemeier@iomedico.com
Contact: Barbara Timm, PhD +49 761 15242 ext 528 barbara.timm@iomedico.com

Locations
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Germany
Gemeinschaftspraxis für Hämatologie und Onkologie Recruiting
Ravensburg, Baden-Wuerttemberg, Germany, 88212
Contact: Thomas Decker, Prof.    +49 751 3661970    thomas.decker@onkonet.eu   
Sponsors and Collaborators
iOMEDICO AG
Novartis Pharmaceuticals
Investigators
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Principal Investigator: Thomas Decker, Prof. Gemeinschaftspraxis für Hämatologie und Onkologie

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Responsible Party: iOMEDICO AG
ClinicalTrials.gov Identifier: NCT03462251     History of Changes
Other Study ID Numbers: IOM-050371
First Posted: March 12, 2018    Key Record Dates
Last Update Posted: July 3, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by iOMEDICO AG:
Breast Cancer
HR positive
HER2 negative
Mamma carcinoma

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Bevacizumab
Capecitabine
Fulvestrant
Aromatase Inhibitors
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists