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Breast CancerPhase 3NCT03905343

Ribociclib-endocrine Combination Therapy Versus Chemotherapy as 1st Line in Visceral mBC

A Phase 3 study testing Ribociclib, Mono-chemotherapy and Endocrine-Therapy in people with Breast Cancer, run by Swiss Cancer Institute at 35 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The aim of this trial is to assess if patients treated with the combination of ribociclib and endocrine therapy respond to treatment as fast as patients treated with chemotherapy only, without decreasing their quality of life (QoL). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Ribociclib, Mono-chemotherapy and Endocrine-Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
35 sitesin 3 countries
Study dates
25 Jun 2019to 15 Apr 2021
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

  • Written informed consent according to national law and ICH/GCP regulations before registration and prior to any trial specific procedures
  • Histologically or cytologically confirmed diagnosis of HR-positive (ER+ ≥10%), HER2-negative advanced stage breast cancer
  • Measurable visceral disease according to RECIST v1.1. Visceral disease in liver and/or lung. Peritoneal and/or pleural metastases only are accepted, with the condition to be measurable
  • No previous systemic anticancer therapy for metastatic disease allowed
  • Mono-chemotherapy is a reasonable treatment option
  • Patients with a prior malignancy and treated with curative intention are eligible if all treatment of that malignancy was completed at least 2 years before randomization and the patient has no evidence of disease at randomization. Less than 2 years is acceptable for adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
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  • Patients with asymptomatic and stable (treated or untreated) central nervous system (CNS) metastases are eligible, provided they meet the following criteria:
  • ≤ 5 CNS lesions with a maximum diameter of the largest lesion of 10 mm
  • No evidence of progression at registration compared to the latest brain imaging (if applicable)
  • No ongoing requirement for corticosteroids as therapy for CNS disease
  • Baseline QoL and pain questionnaires have been completed within 21 days prior to registration
  • Postmenopausal women (without ovarian function suppression)
  • Age ≥ 18 years
  • WHO performance status 0-2
  • Adequate bone marrow function: neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 90 g/L
  • Adequate hepatic function: bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST ≤ 2.5 x ULN, AP ≤ 2.5 x ULN
  • Adequate renal function: estimated glomerular filtration rate (eGFR) > 40 mL/min/1.73m2 (according to CKD-EPI or MDRD formula)
  • Patient is able and willing to swallow trial drug as whole tablet

Who cannot join

  • Visceral crisis (clinical judgment of treating investigator based on the ABC consensus: "visceral crisis is defined as severe organ dysfunction as assessed by signs and symptoms, laboratory studies, and rapid progression of disease. Visceral crisis is not the mere presence of visceral metastases, but implies important visceral compromise leading to a clinical indication for a more rapidly efficacious therapy, particularly since another treatment option at progression will probably not be possible")
  • Symptomatic brain metastases indicative of active disease (defined as new and/or progressive brain metastases at the time of study entry) or leptomeningeal disease
  • Any prior systemic anti-cancer treatment for advanced stage breast cancer
  • Prior treatment with adjuvant CDK4/6 inhibitor
  • Concurrent or recent (within 30 days of randomization) treatment with any other experimental drug. Exception: participation in SAKK 96/12 is allowed
  • Concomitant use of other anti-cancer drugs or radiotherapy, except for local pain control
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  • Planned surgery of metastatic sites in the first 12 treatment weeks
  • Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia)
  • Electrocardiogram (ECG) abnormalities of Q-wave infarction (unless identified ≥ 6 months prior to randomization), or QTc interval >450 msec. The use of concomitant medications with a known significant risk of prolonging the QT interval or inducing Torsades de pointes is not allowed
  • Any concomitant drugs contraindicated for use with the trial drugs according to the approved national product information
  • Known hypersensitivity to trial drug(s) or to any component of the trial drug(s)
  • Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications

Trial locations and contacts

35 sites in 3 countries.

35 sites in 3 countries

Switzerland23 sites

  • Kantonsspital Baden

    Baden, 5404

  • Kantonsspital Baden

    Baden, CH-5404

  • Universitaetsspital-Basel

    Basel, 4031

  • Brustzentrum Basel - Praxis für ambulante Tumortherapie

    Basel, 4052

  • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

    Bellinzona, 6500

  • Inselspital Bern

    Bern, CH-3010

  • Clinique des Grangettes

    Chêne-Bougeries, 1224

  • Kantonsspital Graubuenden

    Chur, CH-7000

  • Hôpital neuchâtelois

    La Chaux-de-Fonds, 2300

  • Centre Hospitalier Universitaire Vaudois

    Lausanne, CH-1011

  • Kantonsspital Liestal

    Liestal, CH-4410

  • Kantonsspital Luzern

    Lucerne, 6000

  • Hirslanden Klinik St. Anna Luzern

    Lucerne, 6006

  • Onkologie Zentrum Spital Männedorf

    Männedorf, 8708

  • Kantonsspital Olten

    Olten, 4600

  • Brustzentrum Ostschweiz

    Sankt Gallen, 9016

  • Kantonsspital - St. Gallen

    Sankt Gallen, CH-9007

  • Hôpital de Sion

    Sion

  • Spital STS AG

    Thun, 3600

  • Kantonsspital Winterthur, Brustzentrum

    Winterthur, 8401

  • Onkologie Bellevue

    Zurich, 8001

  • OnkoZentrum Zürich AG - Klinik im Park

    Zurich, 8038

  • Universitäts Spital Zürich

    Zurich, 8091

Other trials in Switzerland

Belgium8 sites

  • Algemeen Ziekenhuis Klina

    Brasschaat, 2930

  • Grand Hôpital de Charleroi

    Charleroi, 6000

  • Jessa Ziekenhuis

    Hasselt, 3500

  • CHR de la Citadelle

    Liége, 4000

  • CHC Mont Légia

    Liège, 4000

  • CHU de Liege

    Liège, 4000

  • CHU UCL Namur - Site Sainte Elisabeth

    Namur, 5000

  • Clinique-Saint-Pierre

    Ottignies, 1340

Other trials in Belgium

Austria4 sites

  • Med. Univ. Klinik Graz

    Graz, 8036

  • Tirol Kliniken - BrustGesundheitZentrum Tirol

    Innsbruck, 6020

  • Salzburger Landeskliniken - Universitätsklinikum Salzburg

    Salzburg, 5020

  • Universitätsklinik für Frauenheilkunde

    Vienna, 1090

Other trials in Austria

About this study

Official title: Ribociclib-endocrine Combination Therapy Versus Chemotherapy as 1st Line Treatment in Patients With Visceral Metastatic Breast Cancer. A Multicenter, Randomized Phase III Trial.

The aim of this trial is to assess if patients treated with the combination of ribociclib and endocrine therapy respond to treatment as fast as patients treated with chemotherapy only, without decreasing their quality of life (QoL).

Read the detailed description

Breast cancer is the most frequent malignancy in women and the leading cause of cancer mortality in most countries in Europe. Metastatic breast cancer remains an incurable disease with a median overall survival (OS) of 2-4 years and a 5-year survival of only 25%. Patients with hormone receptor (HR)-positive breast cancer involving visceral disease at diagnosis have an even worse outcome.

Many oncologists still prefer to treat visceral disease primarily with chemotherapy rather than with endocrine treatment, thinking to receive a faster response with chemotherapy than with endocrine therapy, especially in patients with clinical symptoms or potentially threatening lesions. However, results from cross-sectional clinical practice studies suggest that endocrine therapy is associated with better quality of life, fewer concerns about side effects, less activity impairment and higher treatment satisfaction compared to chemotherapy. In addition, with the new data of CDK4/6 inhibitors combined with endocrine treatment there is an even better efficacy data available compared to endocrine therapy alone.

The aim of this trial is to assess if patients treated with the combination of ribociclib and endocrine therapy respond to treatment as fast as patients treated with chemotherapy only, without decreasing their quality of life (QoL).

Conditions
Breast Cancer
Being tested
Ribociclib, Mono-chemotherapy, Endocrine-Therapy
Keywords
breast cancer, Visceral metastatic breast cancer, Ribociclib, Ribociclib-endocrine
Medical subject headings
Breast Neoplasms

What participants receive

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

  • RibociclibDrug

    Ribociclib 600mg p.o. d1-21, q4w in combination with endocrine treatment for 3 years.

  • Mono-chemotherapyOther

    mono-chemotherapy for at least 12 weeks (afterwards, maintenance endocrine therapy ± ribociclib inhibitor is allowed) and up to 3 years.

  • Endocrine-TherapyOther

    The choice of endocrine therapy is up to the investigator, but the chosen endocrine therapy has to be registered to be used in combination with ribociclib in the investigated indication.

Study groups in NCT03905343
Study groupRoleWhat they receive
A: endocrine therapy + ribociclibExperimentalNot described
Receives: Drug: Ribociclib; Other: Endocrine-Therapy
B: mono-chemotherapyActive comparatorNot described
Receives: Other: Mono-chemotherapy

What is being measured

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

  1. Quality of life-adjusted early disease control

    A patient will be counted as a success for this endpoint when during the first 12 weeks

    • the response according to RECIST v1.1 is stable disease or better.

    Measured: at 12 weeks.

  2. Quality of life-adjusted early disease control

    A patient will be counted as a success for this endpoint when during the first 12 weeks

    • the QoL according Functional Assessment of Cancer Therapy-Breast Trial Outcome Index [FACT-B TOI] score does not worsen by 5 points or more.

    Measured: at 12 weeks.

Secondary outcomes (11)

  1. Disease Control (DC) at 12 weeks

    A patient will be counted as a success for this endpoint when during the first 12 weeks the response according to RECIST v1.1 is stable disease or better. Patients with missing response assessments within the first 12 weeks will be counted as failure unless there was no progressive disease (PD) documented within the first 12 weeks and the first subsequent assessment also shows no PD

    Measured: week 6, 12.

  2. Objective response rate (ORR)

    ORR is defined as the proportion of patients having achieved complete response (CR) or partial response (PR) during trial treatment. Response will be evaluated according to RECIST v1.1 criteria.

    Measured: week 6, 12, then every 12 weeks up to 3 years or end of trial treatment.

  3. Time to objective response (OR)

    Time to OR will be calculated from randomization until first documented CR or PR according to RECIST v1.1 criteria. Time to OR will be calculated for patients having achieved a CR or PR at any time during trial treatment.

    Measured: week 6, 12, then every 12 weeks up to 3 years or end of trial treatment.

  4. Progression-free survival (PFS)

    PFS is defined as the time from randomization until progression according the RECIST v1.1 criteria or death from any cause, whichever occurs first. Patients not having an event at the time of analysis as well as patients starting a new anti-cancer therapy in the absence of an event will be censored at the date of their last tumor assessment before starting a new anti-cancer treatment, if any.

    Measured: week 6, 12, then every 12 weeks up to 3 years.

  5. Time to treatment failure (TTF)

    TTF is defined as the time from randomization until stopping of trial treatment from any cause. Patients not having an event at the time of analysis will be censored at the date of their last known date of trial treatment.

    Measured: week 6, 12, then every 12 weeks up to 3 years.

  6. Overall survival (OS) at 3 years

    OS at 3 years is determined by the Kaplan-Meier estimator for OS at 3 years. OS is defined as time from randomization to death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

    Measured: week 6, 12, then every 12 weeks up to 3 years.

  7. Changes in overall QoL (FACT-B) until 24 months

    Changes in Functional Assessment of Cancer Therapy-Breast (FACT-B) total score (score range 0-148, higher scores indicate better quality of life)

    Measured: Changes from baseline to 24 months

  8. Time to QoL deterioration

    Time to QoL deterioration is defined as the duration between baseline and first occurrence of a decrease of ≥ 5 points in the FACT-TOI score.

    Measured: From baseline to 24 months

  9. Time to QoL improvement

    Time to QoL improvement is defined as the duration between baseline and first occurrence of an increase of ≥ 5 points in the FACT-TOI score.

    Measured: From baseline to 24 months

  10. Time to pain improvement

    Improvements in pain will be assessed up to 24 months by the item pain severity of the Brief Pain Inventory (BPI), scale range: 0= no pain to 10 = pain as bad as one can imagine.

    Measured: From baseline to 24 months

  11. Adverse events (AEs)

    All AEs will be assessed according to NCI CTCAE v5.0.

    Measured: every 4 weeks up to 3 years.

Timeline

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

  1. First posted5 Apr 2019
  2. Study start25 Jun 2019
  3. Primary completion15 Apr 2021
  4. Study completion15 Apr 2021

Why it stopped: Feasibility (low patient accrual and financial reasons)

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
Model description
This is an international, multicenter, open-label, randomized phase III trial.
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03905343
Sponsor's protocol ID
SAKK 21/18
Other IDs
2018-003648-22, 2018
Status last verified
Jun 2021
First submitted
12 Mar 2019
Last updated
16 Jun 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ribociclib, Mono-chemotherapy and Endocrine-Therapy in people with Breast Cancer, run by Swiss Cancer Institute at 35 sites in 3 countries.

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 18 inclusion and 12 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: stopped early, as of the sponsor's last update on 16 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in Switzerland, Belgium, Austria. 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 was stopped early (reason given: Feasibility (low patient accrual and financial reasons)). Results are not available in the source record.

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?

Quality of life-adjusted early disease control (time frame: at 12 weeks.). The study lists 2 primary outcomes in all. 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 NCT03905343.

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 16 Jun 2021.

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