Relative Bioavailability of Pimasertib in Cancer Patients
6. juli 2017 oppdatert av: EMD Serono
A Multi-Center, Open-Label, Single 60 mg Dose, Two Period, Two Sequence Cross-Over Trial to Investigate the Relative Bioavailability of Two Solid Oral Pimasertib Formulations in Cancer Patients
This is a Phase 1, multi-center, open-label, single-dose, 2 period, 2 sequence cross-over trial to investigate the relative bioavailability of 2 solid oral pimasertib formulations in cancer subjects (Part A), followed by open-label pimasertib administration (Part B and trial extension phase).
Studieoversikt
Status
Fullført
Forhold
Studietype
Intervensjonell
Registrering (Faktiske)
38
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
Massachusetts
-
Rockland, Massachusetts, Forente stater
- Please Contact U.S. Medical Information Located in
-
-
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 80 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- Pathologically confirmed solid tumors, either refractory to standard therapy or for which no effective standard therapy is available, with a measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- An Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to (<=) 1
- Other protocol defined inclusion criteria could apply
Exclusion Criteria:
- Disease conditions or concomitant medication that may significantly influence the conduct of the trial or an abnormal electrocardiogram (ECG) or blood pressure at Screening as defined in the protocol
- Treatment with strong inhibitors or inducers of cytochrome P450 2C19 (CYP2C19) and CYP3A4 including fruit juices or beverages containing these substances
- History of prior mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) kinase (MEK) inhibitor exposure (including, pimasertib) or progression of disease on MEK inhibitors
- Evidence of a retinal vein occlusion (RVO) on fluorescein angiogram or a history of RVO
- Life expectancy of less than 12 weeks
- Other protocol defined exclusion criteria could apply
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: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Pimasertib Capsule/Pimasertib Tablet
|
Pimasertib capsule administration at a single dose of 60 milligram (mg) orally on Day 1 in Part A.
Andre navn:
Pimasertib tablet administration at a single dose of 60 mg orally on Day 3 in Part A.
Andre navn:
Pimasertib tablet administration at a single dose of 60 mg orally on Day 1 in Part A.
Andre navn:
Pimasertib capsule administration at a single dose of 60 mg orally on Day 3 in Part A.
Andre navn:
Subjects completing Part A to receive pimasertib capsule at a dose of 60 mg orally twice daily in cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death.
Andre navn:
|
|
Eksperimentell: Pimasertib Tablet/Pimasertib Capsule
|
Pimasertib capsule administration at a single dose of 60 milligram (mg) orally on Day 1 in Part A.
Andre navn:
Pimasertib tablet administration at a single dose of 60 mg orally on Day 3 in Part A.
Andre navn:
Pimasertib tablet administration at a single dose of 60 mg orally on Day 1 in Part A.
Andre navn:
Pimasertib capsule administration at a single dose of 60 mg orally on Day 3 in Part A.
Andre navn:
Subjects completing Part A to receive pimasertib capsule at a dose of 60 mg orally twice daily in cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
Tidsramme: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet.
|
Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
|
Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t)
Tidsramme: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration was at or above the lower limit of quantification.
|
Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf)
Tidsramme: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tidsramme: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
|
|
Apparent Terminal Half-life (t1/2)
Tidsramme: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
|
|
Apparent Total Body Clearance (CL/f)
Tidsramme: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
|
Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
|
Apparent Volume of Distribution (Vz/f)
Tidsramme: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
|
Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
|
Terminal Rate Constant (λz)
Tidsramme: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
|
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Tidsramme: From the first dose of study drug administration until 30 days after the last dose of study drug administration, assessed up to 14 Months
|
An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Treatment-emergent are events between first dose of study drug administration until 30 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state.
|
From the first dose of study drug administration until 30 days after the last dose of study drug administration, assessed up to 14 Months
|
|
Part B: Number of Subjects Who Experienced Complete Response (CR)
Tidsramme: Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
|
CR as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 defined as disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (<)10 millimeter (mm).
|
Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
|
|
Part B: Number of Subjects Who Experienced Partial Response (PR)
Tidsramme: Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
|
PR as per RECIST v1.1 defined as 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters.
|
Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
|
|
Part B: Number of Subjects Who Experienced Stable Disease (SD)
Tidsramme: Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
|
SD as per RECIST v1.1 defined as neither shrinkage to qualify for PR nor increase to qualify for progressive disease (PD) taking the smallest sum diameters on study as reference.
PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; PD = 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions.
|
Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
|
|
Part B: Number of Subjects Who Experienced Progressive Disease (PD)
Tidsramme: Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
|
PD as per RECIST v1.1 defined as 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions.
|
Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
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.
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)
30. november 2013
Primær fullføring (Faktiske)
31. mai 2014
Studiet fullført (Faktiske)
28. februar 2015
Datoer for studieregistrering
Først innsendt
8. november 2013
Først innsendt som oppfylte QC-kriteriene
18. november 2013
Først lagt ut (Anslag)
25. november 2013
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
15. august 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
6. juli 2017
Sist bekreftet
1. juli 2017
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 200066-013
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .