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A Phase IV Study to Collect Data on the Efficacy and Safety of RIBociclib in Older Women With Breastcancer (RibOB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03956654
Recruitment Status : Recruiting
First Posted : May 21, 2019
Last Update Posted : May 24, 2019
Information provided by (Responsible Party):
prof. dr. Hans Wildiers, Universitaire Ziekenhuizen Leuven

Brief Summary:
The RibOB study is a prospective, open lable, single arm trial which will evaluate the clinical efficacy, overall safety and tolerability of ribociclib in combination with letrozole in older women (≥70 years) with HR+/HER2- aBC and no prior hormonal treatment for advanced disease (as per approved indication).

Condition or disease Intervention/treatment
Breast Cancer Drug: Ribociclib

Detailed Description:
The RibOB study is an observational prospective, open lable single arm phase IV trial which will evaluate the clinical efficacy, overall safety and tolerability of ribociclib in combination with letrozole in older women (≥70 years) with HR+, HER2- advanced breast cancer and no prior hormonal treatment for advanced disease as per the indication approved by the European Medicines Authority (EMA) and as made available by Belgian national authorities in the national health care system. A total of maximum 150 patients will be enrolled for treatment with Letrozole (2.5 mg once daily) + ribociclib 600 mg (day 1 to 21 in a 28 day cycle), which will continue until disease progression, intolerable toxicity or patient/physician decision to withdraw. During the study, patients will be continuously evaluated for disease progression as per national standard of care (approximately every 12 weeks radiologically); for safety; and for quality of life and geriatric assessment components including functional status with QoL assessment and CGA at 3 months (+/- 2 weeks) and at 1 year (+/-2 weeks).

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Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Phase IV Study to Collect Data on the Efficacy and Safety of RIBociclib With Letrozole in Older Women (≥70 Years) With HR+ and HER2- Advanced Breast Cancer (aBC) With no Prior Systemic Therapy for Advanced Disease.
Actual Study Start Date : December 11, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Intervention Details:
  • Drug: Ribociclib
    combination of ribociclib and letrozole
    Other Name: Kisqali

Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 2018-2022 ]
    Clinical efficacy: Progression-free survival (PFS) (defined as the length of time from the start of treatment and death or progression of disease) as determined by the local investigator using RECIST 1.1 rules.

Secondary Outcome Measures :
  1. Time to treatment failure (TTF) [ Time Frame: 2018-2022 ]
    Efficacy: Time to treatment failure (TTF). It is defined as time from date of start of treatment to the date of event defined as the first documented progression, death due to any cause or withdrawal from treatment.

  2. Overall response rate (ORR) [ Time Frame: 2018-2022 ]
    Efficacy: Overall response rate (ORR), for patients with measurable disease as determined locally by investigator according to RECIST 1.1. It is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1.

  3. Overall Survival (OS) [ Time Frame: 2018-2022 ]
    Efficacy: Overall survival (OS). It is defined as the length of time from the start of treatment and death from any cause.

  4. Breast cancer specific survival (BCSS) [ Time Frame: 2018-2022 ]
    Efficacy: Breast cancer specific survival (BCSS). It is defined as the length of time from the start of treatment and death from breast cancer.

  5. Adverse events [ Time Frame: 2018-2022 ]
    Safety: Incidence of Adverse Events according to the NCI-CTCAE 4.03 during study treatment and according to the results of baseline CGA evaluation; Number of patients who stop ribociclib before progression ; number of patients needing dose interruption/reduction.

  6. Treatment discontinuation [ Time Frame: 2018-2022 ]
    Safety: Number of patients who stop ribociclib before progression

  7. Treatment interruption [ Time Frame: 2018-2022 ]
    Safety: number of patients needing dose interruption

  8. Treatment reduction [ Time Frame: 2018-2022 ]
    Safety: number of patients needing dose reduction

  9. PFS / OS [ Time Frame: 2018-2022 ]
    Prediction Modeling I: PFS and OS prognostic model based on clinical/pathologic characteristics

  10. CGA / QoL [ Time Frame: 2018-2022 ]
    Prediction Modeling II: Baseline CGA and QoL and relation with PFS/OS

  11. Quality of Life (1) [ Time Frame: 2018-2022 ]
    Evolution of QoL during study treatment: EORTC QLQ-C30 (modified) and EORTC IL15 questionnaires

  12. Quality of Life (2) [ Time Frame: 2018-2022 ]
    Correlation of baseline QoL with OS

  13. Quality of Life (3) [ Time Frame: 2018-2022 ]
    Correlation of baseline QoL with toxicity grade III-IV

  14. Comprehensive Geriatric Assessment [ Time Frame: 2018-2022 ]
    Evolution of CGA during study treatment

  15. Plasma Biomarker Research (1) [ Time Frame: 2018-2022 ]
    Evolution of potential aging biomarkers during study treatment, and predictive value of baseline aging biomarkers on toxicity, PFS and OS (correcting for the prognostic metastatic index in PFS / OS)

  16. Plasma Biomarker Research (2) [ Time Frame: 2018-2022 ]
    Predictive capacity of thymidine kinase on toxicity, PFS, OS and RR (correcting for the prognostic metastatic index in PFS, OS and RR). Thymidine kinase d1 versus d15 drop, and Thymidine kinase d15 level

  17. Plasma Biomarker Research (3) [ Time Frame: 2018-2022 ]
    Develop a plasma microRNA signature for response to study treatment (pre-dose cycle 3)

  18. Plasma Biomarker Research (4) [ Time Frame: 2018-2022 ]
    Evaluation of plasma antitumor immunity induction by study treatment at day 15 of cycle 1.

Biospecimen Retention:   Samples With DNA
Blood samples will be collected at T0 (i.e. at the time of inclusion of the patient), at T1 (i.e. at day 15 of the first treatment cycle) and at T2 (after 3 months) and in addition to routine laboratory exams, blood drawn will be processed and frozen for future translational research exploring biological aging markers (as predictive markers of functional decline and survival) and biomarkers of response prediction. The central biobanking laboratory in Leuven will provide complete blood sampling sets per patient, containing 3 subsets (one for each time point) with all blood tubes, pre-printed labels and serum/plasma aliquot vials required at that time point, as well as disposable Pasteur pipettes for serum/plasma transfer.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
This study will include older women (defined as ≥70 years) with HR+, HER2- advanced breast cancer who had not received any prior hormonal agent for treatment of advanced disease. It is expected that at least 50% of patients will be older than 75 years.

Inclusion Criteria:

  • Patient is a female ≥ 70 years old at the time of informed consent.
  • Advanced breast cancer (defined as locoregionally recurrent or metastatic not amenable to curative therapy).
  • Histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory (defined as ER and/or PgR ≥1% or Allred >2).
  • HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test as determined by local laboratory testing according to ASCO-CAP guidelines is necessary.
  • Patient has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by local laboratory), preferably tested a maximum of 14 days before enrolment:
  • Patient has signed informed consent obtained before any trial-related activities and according to local guidelines.
  • Subjects must be able to communicate with the investigator and comply with the requirements of the study procedures.

Exclusion Criteria:

  • Patient has a known hypersensitivity to any of the excipients of ribociclib or letrozole.
  • Patients who received any CDK4/6 inhibitor previously.
  • Patient who received any prior systemic antihormonal therapy or chemotherapy for advanced breast cancer.
  • Patient is concurrently using other systemic anti-cancer therapy (except bone modifying agents).
  • Patient with central nervous system (CNS) metastases and/or documented meningeal carcinomatosis unless they meet ALL the following criteria:
  • At least 4 weeks from prior therapy for CNS disease completion (including radiation and/or surgery) to starting the study treatment;
  • Clinically stable CNS lesions at the time of study treatment initiation and not receiving steroids and/or enzyme-inducing anti-epileptic medications for the management of brain metastases for at least 2 weeks (radiological confirmation of brain disease status is not necessary).
  • 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, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
  • Patients who already have or who are at significant risk of developing QTc prolongation are not eligible for the study. This includes patients:
  • with long QT syndrome;
  • with uncontrolled or significant cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina and bradyarrhythmias;
  • with electrolyte abnormalities (potassium, magnesium, sodium and calcium) that are NCI CTCAE 4.03 grade 2 or higher (for details, see table 10 ). Note: phosphate testing is not mandatory, but should the investigator consider measuring it before enrolment, the same rules may be applied

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 identifier (NCT number): NCT03956654

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Contact: Hans Wildiers, prof. dr. 003216346900

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UZ Gasthuisberg Leuven Recruiting
Leuven, Belgium, B-3000
Contact: Hans Wildiers    32 16 346900   
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
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Study Chair: Hans Wildiers, prof. dr. UZ Gasthuisberg

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Responsible Party: prof. dr. Hans Wildiers, adjunct head of clinic, Universitaire Ziekenhuizen Leuven Identifier: NCT03956654     History of Changes
Other Study ID Numbers: s61033
First Posted: May 21, 2019    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by prof. dr. Hans Wildiers, Universitaire Ziekenhuizen Leuven:
breast cancer
geriatric assessment
geriatric oncology
translational research
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs