Clinical trial • Phase III • Oncology

RIBOCICLIB for Breast cancer | Hormone receptor positive HER2 negative breast cancer

Phase III trial of RIBOCICLIB for Breast cancer | Hormone receptor positive HER2 negative breast cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Breast cancer | Hormone receptor positive HER2 negative breast cancer
Trial Stage
Phase III
Drug Modality
Small molecule | Peptide/protein/enzyme | Radiopharmaceutical

Key dates

Initial CTIS Submission Date
14-10-2024
First CTIS Authorization Date
12-11-2024

Trial design

Randomised, comparators include non-steroidal aromatase inhibitors and endocrine therapies: anastrozole 1 mg oral daily (non-steroidal aromatase inhibitor); letrozole 2.5 mg oral daily (non-steroidal aromatase inhibitor); ovarian suppression/ablation options such as goserelin subcutaneous injection (10.8 mg) or leuprorelin acetate intramuscular injection (11.25 mg); fulvestrant 500 mg intramuscular (as second-line therapy). (doses and routes taken from product information present in the ctis record.)-controlled Phase III trial in Netherlands.

Randomised
Yes
Comparator
Comparators include non-steroidal aromatase inhibitors and endocrine therapies: Anastrozole 1 mg oral daily (non-steroidal aromatase inhibitor); Letrozole 2.5 mg oral daily (non-steroidal aromatase inhibitor); ovarian suppression/ablation options such as GOSERELIN subcutaneous injection (10.8 mg) or LEUPRORELIN acetate intramuscular injection (11.25 mg); Fulvestrant 500 mg intramuscular (as second-line therapy). (Doses and routes taken from product information present in the CTIS record.)
Target Sample Size
1050

Eligibility

Recruits 1050 Not a vulnerable population (isVulnerablePopulationSelected=false); trial population restricted to adult women (≥18 years). Informed consent is required from participants as per available subject information and informed consent form documents; no assent procedures for minors are applicable..

Vulnerable Population
Not a vulnerable population (isVulnerablePopulationSelected=false); trial population restricted to adult women (≥18 years). Informed consent is required from participants as per available subject information and informed consent form documents; no assent procedures for minors are applicable.

Inclusion criteria

  • {"criterion_text":"- Adult women (≥ 18 years of age) with proven diagnosis of adenocarcinoma of the breast with locoregional recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated"}
  • {"criterion_text":"- Documentation of histologically or cytologically confirmed diagnosis of estrogen receptor (ER) expression >10% and/or progesterone receptor (PR) expression >10% breast cancer based on local laboratory results. In case ER ≤ 10% and PR >10% the ER and PR expression need to be confirmed in a referral center. Tumor must be HER2-negative as defined by ASCO-CAP guidelines (9). If HER2 status is unavailable then testing must be performed/repeated prior to randomization."}
  • {"criterion_text":"- Previously untreated with any systemic anti-cancer therapy for metastatic HR+ disease, with the exception of recently started (within 28 days of randomization) endocrine therapy."}
  • {"criterion_text":"- Women who are not post-menopausal must receive ovarian ablation or suppression with administration of LHRH agonist."}
  • {"criterion_text":"- Evaluable disease as defined per RECIST v.1.1. Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measurable if disease progression at the treated site after completion of therapy is clearly documented."}
  • {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2."}
  • {"criterion_text":"- Adequate organ and marrow function defined as follows: 1) ANC ≥1,000/mm3 (1.0 x 10e9 /L); 2) Platelets ≥50,000/mm3 (50 x 10e9 /L); 3) Estimated creatinine clearance ≥ 30 mL/min as calculated using the method standard for the institution; 4) Total serum bilirubin ≤1.5 x ULN (≤3.0 x ULN if Gilbert’s disease); 5) AST and ALT ≤3 x ULN (≤5.0 x ULN if liver metastases present);"}
  • {"criterion_text":"- Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤1, except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion."}

Exclusion criteria

  • {"criterion_text":"- Patients with advanced, symptomatic, visceral spread, who are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50% liver involvement)."}
  • {"criterion_text":"- Known hypersensitivity to letrozole or anastrozole, or any of its excipients, or to any CDK4/6 inhibitors excipients."}
  • {"criterion_text":"- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (e.g., radiotherapy, stereotactic surgery) and are clinically stable without the use of steroids for at least 4 weeks before randomization"}
  • {"criterion_text":"- Prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor (i.e. anastrozole or letrozole) with disease recurrence while on or within 12 months of treatment."}
  • {"criterion_text":"- Prior treatment with any CDK4/6 inhibitor."}
  • {"criterion_text":"- Patients treated within the last 7 days prior to randomization with: 1) Food or drugs that are known to be CYP3A4 inhibitors (ie, amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and grapefruit, pomegranate or grapefruit/pomegranate juice); 2) Drugs that are known to be CYP3A4 inducers (ie, carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and St. John’s wort)."}
  • {"criterion_text":"- Major surgery, chemotherapy, any investigational agents, or other anticancer therapy within 2 weeks before randomization. Palliative radiotherapy and/or (neo)adjuvant endocrine treatment within 2 weeks before randomization are allowed, provided that patients have recovered from these treatments. Patients who received prior radiotherapy to ≥25% of bone marrow are not eligible independent of when it was received."}
  • {"criterion_text":"- Diagnosis of any other malignancy prior to randomization, except those that are not believed to influence the patient’s prognosis and do not require any further treatment. This includes, but is not limited to adequately treated basal cell or squamous cell skin cancer and carcinoma in situ of the cervix."}
  • {"criterion_text":"- QTc >480 msec at baseline"}
  • {"criterion_text":"- Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery that influences uptake of oral medication"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Progression-free survival after two lines of treatment (PFS2) defined as time from randomization until one of the following (whichever occurs first): second objective disease progression or objective disease progression on second-line therapy, whichever occurs first, symptomatic deterioration on second-line therapy leading to discontinuation of second-line therapy initiation of chemotherapy for breast cancer or death","definition_or_measurement_approach":"Defined in the endpoint text: time from randomization to second objective disease progression or objective progression on second-line therapy, symptomatic deterioration on second-line therapy leading to discontinuation, initiation of chemotherapy for breast cancer, or death."}

Secondary endpoints

  • {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Quality of life","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Safety and tolerability","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Objective response rate (ORR)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Cost-effectiveness","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Type and incidence of grade 3 and 4 (serious) adverse events ((S)AE) (as graded by NCI CTCAE v4.0) and its relation to study medications.","definition_or_measurement_approach":"Adverse events graded by NCI CTCAE v4.0 and related to study medications."}
  • {"endpoint_text":"- Tumor tissue biomarkers, including genes, proteins and (mi)RNA expression","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Circulating tumor DNA (ctDNA) in plasma","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Nuclear imaging, including FDG-PET and FES-PET","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Pharmacokinetics, -dynamics and -genomics of CDK4/6 inhibitors","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Cognitive functioning as assessed by validated online cognitive tests","definition_or_measurement_approach":"Cognitive functioning assessed using validated online cognitive tests (as stated)."}

Recruitment

Planned Sample Size
1050
Recruitment Window Months
134
Consent Approach
Informed consent is required from adult participants. Subject information and informed consent form documents are provided (documents L1_SIS and ICF SONIA EfFECT side study public; L1_SIS and ICF public). No assent procedures for minors (trial restricted to ≥18 years).

Geography

Total Number Of Sites
62
Total Number Of Participants
1050

Netherlands

Earliest CTIS Part Ii Submission Date
11-11-2024
Latest Decision Or Authorization Date
12-11-2024
Processing Time Days
1
Number Of Sites
62
Number Of Participants
1050

Sites

Site Name
SJG Weert
Department Name
Interne Geneeskunde
Contact Person Name
Myrte Zijlstra
Contact Person Email
m.zijlstra@sjgweert.nl
Site Name
Groene Hart Ziekenhuis
Department Name
Internal medicine / Oncology-Hematology
Contact Person Name
Wendy van der Deure
Contact Person Email
Wendy.van.der.deure@ghz.nl
Site Name
Canisius Wilhelmina Ziekenhuis
Department Name
Oncology-Hematology
Contact Person Name
Caroline Mandigers
Site Name
Rode Kruis Ziekenhuis B.V.
Department Name
Internal medicine
Contact Person Name
Anniek Goosens
Contact Person Email
agoosens@rkz.nl
Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
Oncology
Contact Person Name
Judith Kroep
Contact Person Email
j.r.kroep@lumc.nl
Site Name
Spaarne Gasthuis Stichting
Department Name
Oncology
Contact Person Name
Aart Beeker
Contact Person Email
ABeeker@spaarnegasthuis.nl
Site Name
Ziekenhuis Nij Smellinghe
Department Name
Oncology
Contact Person Name
Sjoerd Hovenga
Site Name
Tjongerschans B.V.
Department Name
Internal medicine
Contact Person Name
Jaap de Boer
Contact Person Email
j.de.boer@tjongerschans.nl
Site Name
Catharina Ziekenhuis Stichting
Department Name
Oncology
Contact Person Name
Birgit Vriens
Site Name
Het Van Weel-Bethesda Ziekenhuis
Department Name
Oncology
Contact Person Name
Anne-Marie Dietvorst
Contact Person Email
a.dietvorst@vanweelbethesda.nl
Site Name
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Department Name
Internal medicine
Contact Person Name
Gabe Sonke
Contact Person Email
g.sonke@nki.nl
Site Name
Saxenburgh Medisch Centrum
Department Name
Internal medicine
Contact Person Name
Susan Kemme
Contact Person Email
s.kemme@sxb.nl
Site Name
Elkerliek Ziekenhuis
Department Name
Oncology-Hematology
Contact Person Name
Manon Pepels
Site Name
Noordwest Ziekenhuisgroep Stichting
Department Name
Internal medicine / Oncology
Contact Person Name
Suzan Vrijaldenhoven
Contact Person Email
s.vrijaldenhoven@nwz.nl
Site Name
Amphia Hospital
Department Name
Oncology
Contact Person Name
Joan Heijns
Contact Person Email
JHeijns@amphia.nl
Site Name
Zuyderland Medisch Centrum Stichting
Department Name
Oncology
Contact Person Name
Franchette van den Berkmortel
Site Name
IJsselland Ziekenhuis
Department Name
Oncology
Contact Person Name
Mijntje Vastbinder
Contact Person Email
mvastbinder@ysl.nl
Site Name
Beatrix Ziekenhuis
Department Name
Oncology
Contact Person Name
Aram van Brussel
Contact Person Email
InterneOncologie@rivas.nl
Site Name
Ziekenhuis St Jansdal
Department Name
Oncology
Contact Person Name
Asia Ropela
Contact Person Email
JA.Ropela@stjansdal.nl
Site Name
Medisch Centrum Leeuwarden B.V.
Department Name
Oncology center Leeuwarden
Contact Person Name
Lisanne Hamming
Contact Person Email
lisanne.hamming@mcl.nl
Site Name
Zaans Medisch Centrum Stichting
Department Name
Oncology
Contact Person Name
Sandra Bakker
Contact Person Email
bakker.sd@zaansmc.nl
Site Name
Haga Hospital
Department Name
Internal medicine
Contact Person Name
Daniël Houtsma
Contact Person Email
d.houtsma@hagaziekenhuis.nl
Site Name
Deventer Ziekenhuis
Department Name
Medical Oncology / Oncology center Deventer
Contact Person Name
Alex Imholz
Contact Person Email
imholza@dz.nl
Site Name
Stichting Radboud universitair medisch centrum
Department Name
Medical Oncology
Contact Person Name
Evelien Kuip
Contact Person Email
evelien.kuip@radboudumc.nl
Site Name
Ziekenhuis Gelderse Vallei Stichting
Department Name
Oncology center
Contact Person Name
Maartje Verstappen
Contact Person Email
verstappenm@zgv.nl
Site Name
Universitair Medisch Centrum Groningen
Department Name
Medical Oncology
Contact Person Name
Geke Hospers
Site Name
Diakonessenhuis Stichting
Department Name
Oncology
Contact Person Name
Lobke van Leeuwen
Contact Person Email
researchoncologie@diakhuis.nl
Site Name
Meander Medisch Centrum Stichting
Department Name
Oncology
Contact Person Name
Christa van Schaik
Site Name
Bernhoven B.V.
Department Name
Internal medicine
Contact Person Name
Allert Vos
Contact Person Email
research@bernhoven.nl
Site Name
Medisch Spectrum Twente
Department Name
Internal medicine
Contact Person Name
Marjolein Pleunis-van Empel
Contact Person Email
ResearchOC@mst.nl
Site Name
Maasziekenhuis Pantein B.V.
Department Name
Oncology
Contact Person Name
Yvonne Kamm
Contact Person Email
y.kamm@pantein.nl
Site Name
Admiraal De Ruyter Ziekenhuis B.V.
Department Name
Internal medicine / Oncology
Contact Person Name
Ellen van Vliet
Contact Person Email
e.vanvliet@adrz.nl
Site Name
Stichting St. Anna Zorggroep
Department Name
Internal medicine
Contact Person Name
Linda van de Winkel
Contact Person Email
l.vande.winkel@st-anna.nl
Site Name
Stichting BovenIJ
Department Name
Interne Geneeskunde
Contact Person Name
Serge Dohmen
Contact Person Email
s.dohmen@bovenij.nl
Site Name
Stichting Martini Ziekenhuis
Department Name
Internal medicine
Contact Person Name
Annette van der Velden
Contact Person Email
a.vandervelden@mzh.nl
Site Name
Treant Ziekenhuiszorg Stichting
Department Name
Internal medicine
Contact Person Name
Nanja Jansen
Contact Person Email
research-onco-hema@treant.nl
Site Name
Ziekenhuis Amstelland
Department Name
Oncology
Contact Person Name
Annette van Zweeden
Contact Person Email
a.vanzweeden@zha.nl
Site Name
Stichting Amsterdam UMC
Department Name
Medical Oncology
Contact Person Name
Inge Konings
Contact Person Email
medonc-mammae@amsterdamumc.nl
Site Name
Universitair Medisch Centrum Utrecht
Department Name
Medical Oncology
Contact Person Name
Rhodé Bijlsma
Contact Person Email
oncostudies@umcutrecht.nl
Site Name
Jeroen Bosch Ziekenhuis Stichting
Department Name
Oncology
Contact Person Name
Jolien Tol
Contact Person Email
j.tol@jbz.nl
Site Name
Sint Antonius Ziekenhuis Stichting
Department Name
Internal medicine
Contact Person Name
Paul de Jong
Site Name
Ikazia Ziekenhuis
Department Name
Oncology
Contact Person Name
Felix de Jongh
Site Name
Alexander Monro Ziekenhuis Stichting
Department Name
Internal medicine
Contact Person Name
Emine Göker
Contact Person Email
research@alexandermonro.nl
Site Name
Albert Schweitzer Ziekenhuis
Department Name
Oncology
Contact Person Name
Jos Kitzen
Contact Person Email
j.j.e.m.kitzen@asz.nl
Site Name
Bravis Ziekenhuis
Department Name
Oncology center
Contact Person Name
Helga Droogendijk
Contact Person Email
h.droogendijk@bravis.nl
Site Name
Antonius Ziekenhuis Sneek
Department Name
Interne Geneeskunde
Contact Person Name
Gerrit Jan Veldhuis
Site Name
Laurentius Ziekenhuis Roermond
Department Name
Internal medicine
Contact Person Name
Kirsten Aaldering
Contact Person Email
interne.geneeskunde@lzr.nl
Site Name
Slingeland Ziekenhuis
Department Name
Internal medicine
Contact Person Name
Kees van Arkel
Contact Person Email
research.onco@slingeland.nl
Site Name
Haaglanden Medisch Centrum Stichting
Department Name
Oncology
Contact Person Name
Rianne Oosterkamp
Site Name
Stichting Elisabeth-Tweesteden Ziekenhuis
Department Name
Oncology-Hematology
Contact Person Name
Anne-Marie van Riel
Contact Person Email
jmgh.vanriel@etz.nl
Site Name
Wilhelmina Ziekenhuis Assen
Department Name
Oncology
Contact Person Name
Peter Nieboer
Contact Person Email
peter.nieboer@wza.nl
Site Name
Ziekenhuis Rivierenland
Department Name
Internal medicine / Oncology
Contact Person Name
Mariëlle Kruijtzer
Contact Person Email
marielle.kruijtzer@zrt.nl
Site Name
Alrijne Zorggroep Stichting
Department Name
Internal medicine
Contact Person Name
Leontine Spierings
Contact Person Email
leaspierings@alrijne.nl
Site Name
Maasstad Ziekenhuis Stichting
Department Name
Oncology
Contact Person Name
Annemieke van der Padt
Site Name
Rijnstate Ziekenhuis Stichting
Department Name
Internal medicine
Contact Person Name
Rutger Koornstra
Contact Person Email
rkoornstra@rijnstate.nl
Site Name
Ziekenhuisgroep Twente Stichting
Department Name
Oncology center
Contact Person Name
Ester Siemerink
Contact Person Email
e.siemerink@zgt.nl
Site Name
ZorgSaam Ziekenhuis
Department Name
Oncology
Contact Person Name
Marjan van Dijk
Contact Person Email
research@zzv.nl
Site Name
Gelre Hospitals
Department Name
Internal medicine
Contact Person Name
Cathrien Tromp-van Driel
Contact Person Email
c.tromp@gelre.nl
Site Name
Reinier de Graaf Groep
Department Name
Oncology
Contact Person Name
Marlies van Bekkum
Contact Person Email
Balieoncohema@rdgg.nl
Site Name
Sint Franciscus Vlietland Groep Stichting
Department Name
Oncology
Contact Person Name
Quirine van Rossum
Contact Person Email
researchinterne@franciscus.nl
Site Name
Tergooiziekenhuizen
Department Name
Internal medicine
Contact Person Name
Sylvia Luykx-de Bakker
Contact Person Email
research@tergooi.nl
Site Name
Dijklander Ziekenhuis
Department Name
Oncology
Contact Person Name
Simone van den Heiligenberg
Site Name
Stichting OLVG
Department Name
Internal medicine / Oncology
Contact Person Name
Emile Kerver
Site Name
Isala Klinieken Stichting
Department Name
Oncology center
Contact Person Name
Aafke Honkoop
Site Name
Streekziekenhuis Koningin Beatrix
Department Name
Oncology
Contact Person Name
Marleen Duizer
Contact Person Email
m.duizer@skbwinterswijk.nl
Site Name
Stichting Viecuri Medisch Centrum voor Noord-Limburg
Department Name
Internal medicine / Oncology
Contact Person Name
Eline Boon
Contact Person Email
elineboon@viecuri.nl
Site Name
Maxima Medisch Centrum
Department Name
Oncology
Contact Person Name
Wouter Dercksen
Contact Person Email
secr.MOC@mmc.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Oncology
Contact Person Name
Agnes Jager
Contact Person Email
a.jager@erasmusmc.nl
Site Name
Flevoziekenhuis Stichting
Department Name
Internal medicine
Contact Person Name
Dirkje Sommeijer
Contact Person Email
dsommeijer@flevoziekenhuis.nl

Sponsor

Primary sponsor

Full Name
BOOG Study Center B.V.
Organisation Type
Laboratory/Research/Testing facility
Country Of Registered Address
Netherlands

Third parties

  • {"country":"Netherlands","full_name":"Amsterdam UMC Stichting","duties_or_roles":"[{\"id\":442577,\"code\":\"11\"},{\"id\":442578,\"code\":\"13\"}]","organisation_type":"Patient organisation/association"}
  • {"country":"Netherlands","full_name":"Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)","duties_or_roles":"[{\"id\":442579,\"code\":\"11\"},{\"id\":442580,\"code\":\"13\"},{\"id\":442581,\"code\":\"4\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Netherlands","full_name":"Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting","duties_or_roles":"[{\"id\":442573,\"code\":\"10\"},{\"id\":442574,\"code\":\"11\"},{\"id\":442575,\"code\":\"13\"},{\"id\":442576,\"code\":\"4\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Netherlands","full_name":"IKNL","duties_or_roles":"[{\"id\":442569,\"code\":\"1\"},{\"id\":442570,\"code\":\"6\"},{\"id\":442571,\"code\":\"7\"},{\"id\":442572,\"code\":\"8\"}]","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
Kisqali 200 mg film-coated tablets
Active Substance
RIBOCICLIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumber: EU/1/17/1221/003 etc.)
Starting Dose
Kisqali 200 mg film-coated tablets
Dose Levels
200 mg
Maximum Dose
600
Investigational Product Name
IBRANCE 75 mg/100 mg/125 mg film-coated tablets
Active Substance
PALBOCICLIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumbers: EU/1/16/1147/010 etc.)
Starting Dose
IBRANCE 75 mg/100 mg/125 mg film-coated tablets
Dose Levels
75 mg | 100 mg | 125 mg
Maximum Dose
125
Investigational Product Name
Verzenios 50 mg/100 mg/150 mg film-coated tablets
Active Substance
ABEMACICLIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumbers: EU/1/18/1307/004 etc.)
Starting Dose
Verzenios 50 mg/100 mg/150 mg film-coated tablets
Dose Levels
50 mg | 100 mg | 150 mg
Maximum Dose
300
Combination Treatment
Yes

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