Display again
SNCTP000002943 | NCT02614794 | BASEC2018-01122

Studio in pazienti affetti da tumore mammario avanzato

Data source: BASEC (Imported from 30.11.2021), WHO (Imported from 18.04.2021)
Changed: 25.11.2021
Disease category: Breast Cancer

Brief description of trial (Data source: BASEC)

La partecipazione allo studio è aperta a qualsiasi paziente di sesso femminile o maschile di età superiore a 18 anni cui è stato diagnosticato un tumore mammario avanzato HER2-positivo non operabile, che non ha risposto in misura sufficiente ai trattamenti precedenti o il cui ultimo trattamento non è stato tollerato.
Parteciperanno allo studio circa 600 pazienti in circa 200 ospedali in vari Paesi del mondo. I pazienti saranno randomizzati secondo un rapporto di 2:1 a ricevere tucatinib e i trattamenti approvati (capecitabina e trastuzumab) o il placebo e i trattamenti standard sopramenzionati. Randomizzazione significa che l’assegnazione avviene aleatoriamente, come nel lancio di una monetina. La possibilità di essere assegnati a tucatinib è pari al 66,7%. Il periodo di trattamento può avere una durata variabile e dipende dalla sicurezza e dall’efficacia dei trattamenti antitumorali. I pazienti potranno partecipare allo studio finché tollerano i test, le procedure e i trattamenti della ricerca, e la malattia è stabile o in miglioramento.
Prima della fase di trattamento verranno eseguite diverse valutazioni, ad es. valutazioni radiologiche, esami del sangue, storia medica, segni vitali, ECG, ecc. Dopo l’inizio del trattamento, le visite presso l’ospedale avranno luogo in cicli della durata di 21 giorni ciascuno. Per i primi 2 cicli il paziente dovrà recarsi in ospedale anche il Giorno 12. Infine, si recherà in ospedale dopo 30 giorni dal completamento o dall’interruzione del trattamento, e a cadenza trimestrale avranno luogo ulteriori contatti

Health conditions investigated (Data source: BASEC)

Pazienti con diagnosi di tumore mammario avanzato non operabile e già pretrattato, in cui il test sul tessuto tumorale ha evidenziato la presenza della proteina HER2 nelle cellule tumorali.
Tucatinib è un nuovo medicamento sperimentale in fase di studio come trattamento aggiuntivo alla terapia di routine con capecitabina e trastuzumab (due trattamenti approvati) per questo tipo di tumore. Lo scopo di questo studio è valutare l’efficacia e la sicurezza del trattamento sperimentale in studio con tucatinib (altresì noto come ONT-380) in aggiunta al trattamento con le terapie antitumorali usate di routine (capecitabina e trastuzumab), rispetto al trattamento con capecitabina e trastuzumab più il placebo. Il placebo viene aggiunto ai trattamenti usati di routine per mantenere lo studio in cieco. In questo né il paziente né il medico sono a conoscenza di quale trattamento viene somministrato e nessuno è influenzato in modo positivo o negativo al momento dell’analisi dell’efficacia e della sicurezza dei due gruppi di trattamento.
Un altro scopo di questo studio di ricerca è confrontare il tempo impiegato per la crescita delle cellule tumorali, in base alle valutazioni radiologiche, nei pazienti trattati con tucatinib in aggiunta ai trattamenti standard o solamente con i trattamenti standard. Tutti i pazienti riceveranno capecitabina e trastuzumab. I ricercatori sperano che l’aggiunta di tucatinib ai trattamenti standard aiuti a distruggere più efficacemente le cellule tumorali o ad arrestarne la crescita e la diffusione

Health conditions (Data source: WHO)

HER2 Positive Breast Cancer

Rare disease (Data source: BASEC)

Yes

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

La ragione per la quale viene condotto questo studio è confrontare la sicurezza e l’efficacia del medicamento sperimentale tucatinib, altresì noto come ONT-380, in associazione a due medicamenti approvati (capecitabina e trastuzumab) in pazienti affetti da tumore mammario avanzato HER2+, con la sicurezza e l’efficacia del placebo somministrato insieme ai due medicamenti approvati capecitabina e trastuzumab.
Il tumore mammario è la forma tumorale più comune tra le donne di tutto il mondo. In circa il 20% dei casi di tumore mammario si riscontra la sovraespressione del recettore 2 per il fattore di crescita epidermico umano (Human Epidermal Growth Factor Receptor, HER2). Nel caso dei tumori HER2+, le cellule tumorali presentano un numero anormalmente alto di recettori HER2. Inoltre, questo tipo di tumore tende a crescere e diffondersi più velocemente rispetto ai tumori negativi all’HER2. Il medicamento sperimentale tucatinib agisce sulle cellule con sovraespressione dell’HER2.

Poiché lo sviluppo di nuove terapie per il tumore mammario metastatico contenente la proteina HER2 ha portato a un prolungamento significativo della sopravvivenza media di questi pazienti, si intende testare questo medicamento sperimentale in aggiunta ai trattamenti antitumorali approvati contro le cellule del tumore mammario HER2+. L’effetto di questo trattamento aggiunto potrebbe costituire un nuovo approccio per combattere il tumore.

Interventions (Data source: WHO)

Drug: tucatinib;Drug: capecitabine;Drug: trastuzumab;Drug: placebo

Criteria for participation in trial (Data source: BASEC)

• Pazienti affetti da tumore mammario HER2+
• Trattamento precedente con terapia standard per il tumore mammario
• Peggioramento del tumore mammario dopo l’ultima terapia medica o ultima terapia non tollerata
• Pazienti di età pari ad almeno 18 anni e, per le pazienti di sesso femminile potenzialmente fertili, test di gravidanza negativo

Exclusion criteria (Data source: BASEC)

• Lapatinib negli ultimi 12 mesi
• Neratinib, afatinib, capecitabina o altri trattamenti sperimentali per i tumori HER2+ in qualsiasi momento precedente
• Storia di reazioni allergiche ai trattamenti farmacologici per il tumore mammario HER2+
• Storia di esposizione a una dose cumulativa specifica di antracicline
• Storia di trattamenti con qualsiasi terapia antitumorale (tra cui terapia ormonale), radioterapia non diretta al SNC o agenti sperimentali nelle ultime 3 settimane

Inclusion/Exclusion Criteria (Data source: WHO)


Double-blind Phase Inclusion Criteria

- Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ
hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization
(FISH) methodology

- Received previous treatment with trastuzumab, pertuzumab, and T-DM1

- Progression of unresectable locally advanced or metastatic breast cancer after last
systemic therapy (as confirmed by investigator), or be intolerant of last systemic
therapy

- Have measurable or non-measurable disease assessable by RECIST 1.1

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Adequate hepatic and renal function and hematologic parameters

- Left ventricular ejection fraction (LVEF) = 50%

- CNS Inclusion - Based on screening brain magnetic resonance imaging (MRI), patients
must have one of the following:

1. No evidence of brain metastases

2. Untreated brain metastases not needing immediate local therapy

3. Previously treated brain metastases not needing immediate local therapy

1. Brain metastases previously treated with local therapy may either be stable
since treatment or may have progressed since prior local CNS therapy

2. Patients treated with CNS local therapy for newly identified lesions found
on contrast brain MRI performed during screening for this study may be
eligible to enroll if the following criteria are met:

i. Time since whole brain radiation therapy (WBRT) is = 21 days prior to first
dose of study treatment, time since stereotactic radiosurgery (SRS) is = 7 days
prior to first dose of study treatment, or time since surgical resection is = 28
days.

ii. Other sites of disease assessable by RECIST 1.1 are present

4. Relevant records of any CNS treatment must be available to allow for
classification of target and non-target lesions

Double-blind Phase Exclusion Criteria

- Previously been treated with:

1. lapatinib within 12 months of starting study treatment (except in cases where
lapatinib was given for = 21 days and was discontinued for reasons other than
disease progression or toxicity)

2. neratinib, afatinib, or other investigational HER2/epidermal growth factor
receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) at any time previously

3. capecitabine (or other fluoropyrimidine) for metastatic disease except in cases
where capecitabine was given for < 21 days and was discontinued for reasons other
than disease progression or toxicity. Patients who have received capecitabine for
adjuvant or neoadjuvant treatment at least 12 months prior to starting study
treatment are eligible.

- Clinically significant cardiopulmonary disease

- Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease

- Positive for human immunodeficiency virus (HIV)

- Unable for any reason to undergo MRI of the brain

- Have used a strong CYP3A4 or CYP2C8 inhibitor within 5 half-lives of the inhibitor, or
a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment

- Have known dihydropyrimidine dehydrogenase deficiency (DPD)

- CNS Exclusion - Based on screening brain MRI, patients must not have any of the
following:

1. Any untreated brain lesions > 2.0 cm in size, unless approved by medical monitor

2. Ongoing use of systemic corticosteroids for control of symptoms of brain
metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent)

3. Any brain lesion thought to require immediate local therapy. Patients who undergo
local treatment for such lesions identified by screening contrast brain MRI may
still be eligible for the study based on criteria described under CNS inclusion
criteria

4. Known or suspected leptomeningeal disease (LMD)

5. Poorly controlled seizures Unblinded Phase Crossover Inclusion Criteria -
Participants who were randomized to the control arm (placebo + trastuzumab +
capecitabine) must meet the following criteria to be eligible to crossover to the
experimental arm.

- Have measurable or non-measurable disease assessable by RECIST 1.1

- For patients who were randomized to the control arm and on the long-term follow-up
period at the time of crossover screening: have progression of unresectable locally
advanced or metastatic breast cancer after last systemic therapy (as confirmed by
investigator), or be intolerant of last systemic therapy.

- Have an ECOG Performance Status of 0 or 1

- Have a life expectancy of at least 6 months

- Have adequate hepatic and renal function and hematologic parameters

- Left ventricular ejection fraction (LVEF) = 50%

- CNS Inclusion - Based on screening brain magnetic resonance imaging (MRI), patients
must have one of the following:

i. No evidence of brain metastases ii. Untreated brain metastases not needing
immediate local therapy iii. Previously treated brain metastases not needing immediate
local therapy

- Brain metastases previously treated with local therapy may either be stable since
treatment or may have progressed since prior local CNS therapy

- Patients treated with CNS local therapy for newly identified lesions found on contrast
brain MRI performed during screening for this study may be eligible to enroll if the
following criteria are met:

1. Time since whole brain radiation therapy (WBRT) is = 21 days prior to first dose
of study treatment, time since stereotactic radiosurgery (SRS) is = 7 days prior
to first dose of study treatment, or time since surgical resection is = 28 days.

2. Other sites of disease assessable by RECIST 1.1 are present Unblinded Phase
Crossover Exclusion Criteria - Participants who were randomized to the control
arm (placebo + trastuzumab + capecitabine) will be excluded from the crossover to
the experimental arm for any of the following reasons.

- Discontinuation of study treatment due to an adverse event while on the double-blind
phase of the study. If the adverse event leading to discontinuation of study treatment
has resolved, the patient may be allowed to crossover with approval from the medical
monitor.

- History of exposure to the following cumulative doses of anthracyclines:<

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT02614794

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT02614794

Further information on trial

Date trial registered

20.11.2015

Incorporation of the first participant

28.01.2016

Recruitment status

Active, not recruiting

Academic title (Data source: WHO)

Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

Progression-free Survival (PFS) Per RECIST 1.1 as Determined by Blinded Independent Central Review (BICR)

Secundary end point (Data source: WHO)

Pharmacokinetic Measure: ONT-993;Pharmacokinetic Measure: Ctrough of Tucatinib;Incidence of Health Resources Utilization;Frequency of Dose Modifications;Incidence of Adverse Events (AEs);CBR Per RECIST 1.1 as Determined by Investigator Assessment;Clinical Benefit Rate (CBR) as Determined by BICR Per RECIST 1.1;DOR Per RECIST 1.1 as Determined by Investigator Assessment;Duration of Response (DOR) Per RECIST 1.1 as Determined by BICR;PFS Per RECIST 1.1 as Determined by Investigator Assessment;ORR Per RECIST 1.1 as Determined by Investigator Assessment;Confirmed Objective Response Rate (ORR) Per RECIST 1.1 as Determined by BICR;Overall Survival (OS);PFS in Patients With Brain Metastases at Baseline Using RECIST 1.1 as Determined by BICR

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

https://clinicaltrials.gov/ct2/show/results/NCT02614794

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Bellinzona

Countries (Data source: WHO)

Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Israel, Italy, Portugal, Spain, Switzerland, United Kingdom, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Dr. Simona Di Lascio
+41 91 811 34 03
simona.dilascio@eoc.ch

Contact for general information (Data source: WHO)

Jorge Ramos, DO;Corinna Palanca-Wessels, MD, PhD
Seagen Inc.

Contact for scientific information (Data source: WHO)

Jorge Ramos, DO;Corinna Palanca-Wessels, MD, PhD
Seagen Inc.

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Seagen Inc.

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Comitato etico cantonale Ticino

Date of authorisation by the ethics committee

03.08.2018

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2018-01122

Secondary ID (Data source: WHO)

2015-002801-12
ONT-380-206