Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer (SELECT-3)
12. mars 2018 oppdatert av: AstraZeneca
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination With First Line Chemotherapy Regimens in Patients With Non-Small Cell Lung Cancer (NSCLC)
This is a Phase I, open label multicentre study of selumetinib administered orally in combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC. The study has been designed to allow an investigation of the optimal dose of selumetinib in combination with various standard first line double-platinum chemotherapy regimens. Initial assessment will be based on tolerability of selumetinib in combination with one or more selected regimens that are considered to be tolerated also being assessed for preliminary evidence of activity.
This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.
Studieoversikt
Status
Fullført
Intervensjon / Behandling
Detaljert beskrivelse
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination with First Line Chemotherapy Regimens in Patients with Non-Small Cell Lung Cancer (NSCLC)
Studietype
Intervensjonell
Registrering (Faktiske)
55
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Glasgow, Storbritannia, G12 0YN
- Research Site
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London, Storbritannia, W1G 6AD
- Research Site
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Manchester, Storbritannia, M20 4BX
- Research Site
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Newcastle upon Tyne, Storbritannia, NE7 7DN
- Research Site
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 99 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- Provision of signed, written and dated consent prior to any study specific procedures
- Male or female, aged 18 years or older
- Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
- Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
- Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information
Exclusion Criteria:
- Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
- Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
- Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
- Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: Selumetinib+standard chemotherapy
Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin
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2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin).
If tolerated - next cohort 3 x 25mg capsules bd continuously.
if higher doses are explored, required number of capsules will be provided.
Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy
1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle.
If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
75 mg/m2 iv on Day 1 of each 21 day cycle.
If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
If it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle
Gemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
Tidsramme: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
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Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting
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The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Best Objective Response
Tidsramme: Screening, week 6 and week 12
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The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression.
Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of >=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm
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Screening, week 6 and week 12
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Percentage Change From Baseline at 6 Weeks in Target Lesion Size
Tidsramme: Week 6
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The percentage change in the sum of the diameters of target lesions
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Week 6
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Best Percentage Change From Baseline in Target Lesion Size
Tidsramme: Screening, week 6 and week 12
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The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression.
Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions
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Screening, week 6 and week 12
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Objective Response Rate (ORR)
Tidsramme: Up until progression or last evaluable assessment in the absence of progression, up to 9 months
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The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression.
Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR
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Up until progression or last evaluable assessment in the absence of progression, up to 9 months
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AUC (0-tau)
Tidsramme: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau)
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Cmax,ss
Tidsramme: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Maximum plasma concentration at steady state
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Tmax,ss
Tidsramme: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Time to reach maximum plasma concentration at steady state
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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CL/F
Tidsramme: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Apparent oral plasma clearance
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studieleder: Gabriella Mariani, MD, AstraZeneca UK, MSD
- Hovedetterforsker: Emma Dean, BMEDSCI, BM, BS, PHD, The Christie NHS Foundation Trust, UK
- Hovedetterforsker: Fiona Blackhall, PhD, FRCP, The Christie NHS Foundation Trust Clinical Trials Unit; UK
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
4. april 2013
Primær fullføring (Faktiske)
4. januar 2016
Studiet fullført (Faktiske)
4. januar 2016
Datoer for studieregistrering
Først innsendt
8. mars 2013
Først innsendt som oppfylte QC-kriteriene
11. mars 2013
Først lagt ut (Anslag)
12. mars 2013
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
13. mars 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
12. mars 2018
Sist bekreftet
1. mars 2018
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Sykdommer i luftveiene
- Neoplasmer
- Lungesykdommer
- Neoplasmer etter nettsted
- Neoplasmer i luftveiene
- Thoracale neoplasmer
- Karsinom, bronkogent
- Bronkiale neoplasmer
- Lungeneoplasmer
- Karsinom, ikke-småcellet lunge
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Antivirale midler
- Nukleinsyresyntesehemmere
- Enzymhemmere
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Folsyreantagonister
- Gemcitabin
- Karboplatin
- Cisplatin
- Pemetrexed
Andre studie-ID-numre
- D1532C00070
- EudraCT number: 2012-005202-22
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