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

NCT03905343 | Terminated Phase 3 DMC

• 2 other identifiers: SAKK 21/182018-003648-22
• Study Type: interventional
• Target: 25
• Locations: 3 countries
• Sites: 35

Brief 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).

Conditions

Breast Cancer

Keywords

breast cancer; Visceral metastatic breast cancer; Ribociclib; Ribociclib-endocrine

Outcome Measures

Primary Outcomes (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 response according to RECIST v1.1 is stable disease or better.

  at 12 weeks.

• 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.

  at 12 weeks.

Secondary Outcomes (11)

• Disease Control (DC) at 12 weeks

  week 6, 12.

• Objective response rate (ORR)

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

• Time to objective response (OR)

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

• Progression-free survival (PFS)

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

• Time to treatment failure (TTF)

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

Study Arms (2)

A: endocrine therapy + ribociclib

EXPERIMENTAL

Drug: Ribociclib; Other: Endocrine-Therapy

B: mono-chemotherapy

ACTIVE COMPARATOR

Other: Mono-chemotherapy

Interventions

Ribociclib DRUG

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

A: endocrine therapy + ribociclib

Mono-chemotherapy OTHER

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

B: mono-chemotherapy

Endocrine-Therapy OTHER

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.

A: endocrine therapy + ribociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Swiss Cancer Institute: lead
• The Belgian Society of Medical Oncology: collaborator

Study Sites (35)

Med. Univ. Klinik Graz

Graz, 8036, Austria

Location

Tirol Kliniken - BrustGesundheitZentrum Tirol

Innsbruck, 6020, Austria

Location

Salzburger Landeskliniken - Universitätsklinikum Salzburg

Salzburg, 5020, Austria

Location

Universitätsklinik für Frauenheilkunde

Vienna, 1090, Austria

Location

Algemeen Ziekenhuis Klina

Brasschaat, 2930, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

Location

Jessa Ziekenhuis

Hasselt, 3500, Belgium

Location

CHC Mont Légia

Liège, 4000, Belgium

Location

CHU de Liege

Liège, 4000, Belgium

Location

CHR de la Citadelle

Liége, 4000, Belgium

Location

CHU UCL Namur - Site Sainte Elisabeth

Namur, 5000, Belgium

Location

Clinique-Saint-Pierre

Ottignies, 1340, Belgium

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Universitaetsspital-Basel

Basel, 4031, Switzerland

Location

Brustzentrum Basel - Praxis für ambulante Tumortherapie

Basel, 4052, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Clinique des Grangettes

Chêne-Bougeries, 1224, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Hôpital neuchâtelois

La Chaux-de-Fonds, 2300, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Liestal

Liestal, CH-4410, Switzerland

Location

Kantonsspital Luzern

Lucerne, 6000, Switzerland

Location

Hirslanden Klinik St. Anna Luzern

Lucerne, 6006, Switzerland

Location

Onkologie Zentrum Spital Männedorf

Männedorf, 8708, Switzerland

Location

Kantonsspital Olten

Olten, 4600, Switzerland

Location

Brustzentrum Ostschweiz

Sankt Gallen, 9016, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Hôpital de Sion

Sion, Switzerland

Location

Spital STS AG

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur, Brustzentrum

Winterthur, 8401, Switzerland

Location

Onkologie Bellevue

Zurich, 8001, Switzerland

Location

OnkoZentrum Zürich AG - Klinik im Park

Zurich, 8038, Switzerland

Location

Universitäts Spital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib

Condition Hierarchy (Ancestors)

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

Study Officials

• Thomas Ruhstaller, Prof

  Kantonsspital St. Gallen - Breast Center St. Gallen

  STUDY CHAIR

Study Design

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

Model Details: This is an international, multicenter, open-label, randomized phase III trial.

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: April 5, 2019
• Study Start: June 25, 2019
• Primary Completion: April 15, 2021
• Study Completion: April 15, 2021
• Last Updated: June 16, 2021

Record last verified: 2021-06

Locations

BE (8); AU (4); CH (23)