- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01136733
A Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior Vascular Endothelial Growth Factor (VEGF)-Targeted Treatment
7 febbraio 2019 aggiornato da: Eisai Inc.
An Open-Label, Multicenter, Phase 1b/2 Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment
This is an open-label, multicenter, Phase 1b/2 study of lenvatinib alone and in combination with everolimus in subjects with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted treatment.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
173
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Brno, Cechia
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Olomouc, Cechia
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Prague, Cechia
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Gdansk, Polonia
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Lodz, Polonia
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Szczecin, Polonia
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Warsaw, Polonia
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Bristol, Regno Unito
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Cambridge, Regno Unito
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Cardiff, Regno Unito
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Glasgow, Regno Unito
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Guildford, Regno Unito
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Ipswich, Regno Unito
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Leicester, Regno Unito
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London, Regno Unito
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Manchester, Regno Unito
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Southampton, Regno Unito
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Surrey, Regno Unito
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Wirral, Regno Unito
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Barcelona, Spagna
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Cordoba, Spagna
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Madrid, Spagna
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Pamplona, Spagna
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Arizona
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Tucson, Arizona, Stati Uniti
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California
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Orange, California, Stati Uniti
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San Diego, California, Stati Uniti
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Florida
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Tampa, Florida, Stati Uniti
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Illinois
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Joliet, Illinois, Stati Uniti
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Kentucky
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Louisville, Kentucky, Stati Uniti
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Maryland
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Annapolis, Maryland, Stati Uniti
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Bethesda, Maryland, Stati Uniti
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Massachusetts
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Boston, Massachusetts, Stati Uniti
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Mississippi
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Tupelo, Mississippi, Stati Uniti
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New York
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New York, New York, Stati Uniti
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Oklahoma
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Tulsa, Oklahoma, Stati Uniti
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South Carolina
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Charleston, South Carolina, Stati Uniti
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Texas
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Dallas, Texas, Stati Uniti
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 99 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Select Inclusion Criteria:
- Histologically confirmed diagnosis of renal cell carcinoma.
- Phase 2: Histological or cytological confirmation of predominant clear cell renal cell carcinoma (RCC) (original tissue diagnosis of RCC is acceptable).
- Documented evidence of unresectable advanced or metastatic RCC. Phase 2: Radiographic evidence of disease progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- Phase 2: One prior vascular endothelial growth factor (VEGF)-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, bevacizumab, axitinib, vatalanib, AV951/tivozanib) for unresectable advanced or metastatic RCC.
- Phase 2: Measurable disease meeting the following criteria: a.) at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short axis diameter for a lymph node which is serially measurable according to Modified RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI) or photography. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
Select Exclusion Criteria:
Phase 1b or Phase 2 specific per below:
- Phase 1b only: Subjects with untreated or unstable metastasis to the central nervous system (CNS) are excluded. Subjects who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are eligible for Phase 1b only. Phase 2 only: Subjects with CNS (e.g., brain or leptomeningeal) metastasis are excluded.
- Phase 2 only: More than one prior VEGF-targeted treatment for unresectable advanced or metastatic RCC.
Phase 1b or Phase 2 specific per below:
- Phase 1b only: Prior exposure to lenvatinib. Phase 2 only: Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor.
- Subjects should not have received any anticancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anticancer treatment. Major surgery within 3 weeks prior to the first dose of study drug.
- Subjects having greater than 1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria.
- Subjects with urine protein greater than or equal to 1 g/24 hours will be ineligible. Uncontrolled diabetes as defined by fasting serum glucose at 1.5 x ULN.
- Phase 2 only: Active malignancy (except for renal cell carcinoma, melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
- Known intolerance to any of the study drugs (or any of the excipients) and/or known hypersensitivity to rapamycins (e.g., sirolimus, everolimus, temsirolimus) or any of the excipients.
- Phase 1b only: Subjects who discontinued prior tyrosine kinase inhibitor due to toxicity will be ineligible.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: Lenvatinib
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taken orally, once a day
Altri nomi:
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Sperimentale: Lenvatinib plus Everolimus
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taken orally, once a day
Altri nomi:
taken orally, once a day
Altri nomi:
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Comparatore attivo: Everolimus
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taken orally, once a day
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT)
Lasso di tempo: First dose of study drug (Cycle 1 Day 1) to end of first 4 weeks of therapy (Cycle 1)
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A DLT was defined as either a treatment-related failure to administer greater than or equal to (>=) 75% of the planned dosage of lenvatinib/everolimus or a specific National Cancer Institute Common Toxicity Criteria (NCI CTC) >= Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care daily living activities) hematologic or nonhematologic toxicities considered to be possibly related to lenvatinib and/or everolimus therapy assessed during the first treatment cycle of each dose level.
Higher grade indicates more severe toxicity.
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First dose of study drug (Cycle 1 Day 1) to end of first 4 weeks of therapy (Cycle 1)
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Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 (RP2) Dose
Lasso di tempo: First dose of study drug (Cycle 1 Day 1) to end of Cycle 2 (1 cycle = 28 days/4 weeks)
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The highest dose level resulting in 0 or 1 DLT in 6 participants was to be considered the MTD of Phase 1b.
Once the MTD was established, the participant cohort was expanded to a minimum of 10 participants.
The MTD was confirmed by assessing DLTs during Cycle 1 and intolerable toxicities (i.e., not manageable with dose interruption and/or reduction) during Cycle 2 of therapy.
Once the dose of lenvatinib/everolimus combination to be used in the succeeding Phase 2 part of the study was established, enrollment into Phase 2 was started.
The RP2 dose was the same as the confirmed MTD and was used for the Phase 2 Treatment Arm A of this study.
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First dose of study drug (Cycle 1 Day 1) to end of Cycle 2 (1 cycle = 28 days/4 weeks)
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Phase 2: Progression-Free Survival (PFS)
Lasso di tempo: Date of randomization into Phase 2 (Cycle 1 Day 1) to the date of first documentation of disease progression or death (whichever occurred first), assessed up to data cutoff date (13 Jun 2014), up to approximately 2 years and 3 months
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PFS was defined as the time (in months) from the date of first dose of study drug to the first documentation of disease progression or death, whichever occurred first.
Kaplan-Meier (K-M) estimates were used to estimate median PFS, presented with 2-sided 95% confidence intervals (CIs).
Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease using computed tomography (CT) or magnetic resonance imaging (MRI) and scan acquisition techniques (including use or nonuse of intravenous (IV) contrast).
Tumor response was determined at the site by the investigator and radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in the evaluation of the tumor assessment scans.
The date of objective disease progression was defined as the earliest date of radiological disease progression.
Participants removed from therapy due to clinical progression with no radiologic confirmation were censored at their last radiologic assessment date.
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Date of randomization into Phase 2 (Cycle 1 Day 1) to the date of first documentation of disease progression or death (whichever occurred first), assessed up to data cutoff date (13 Jun 2014), up to approximately 2 years and 3 months
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Phase 2: Overall Survival (OS)
Lasso di tempo: Randomization (Cycle 1 Day 1) until date of death from any cause, assessed up to the data cutoff date (10 Dec 2014), up to approximately 2 years and 9 months
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OS was defined as the time (in months) from the date of randomization until date of death from any cause.
Median survival time was calculated using K-M estimate for each treatment arm and presented with 2-sided 95% CIs.
Participants who were lost to follow-up or alive at the data cutoff date (10 Dec 2014) were censored at the date the participants were last known to be alive.
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Randomization (Cycle 1 Day 1) until date of death from any cause, assessed up to the data cutoff date (10 Dec 2014), up to approximately 2 years and 9 months
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Phase 2: Objective Response Rate (ORR)
Lasso di tempo: Randomization (Cycle 1 Day 1) until first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
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The ORR was defined as the percentage of participants who had the best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator, using RECIST 1.1 in the evaluation of MRI or CT scans of targeted lesions.
Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease).
The BOR was defined as the best response recorded from the start of the study treatment until discontinuation from the study.
CR was defined as disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm.
PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
ORR = CR + PR was calculated with exact 95% CIs using the method of Clopper and Pearson.
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Randomization (Cycle 1 Day 1) until first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
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Disease Control Rate (DCR)
Lasso di tempo: Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
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The DCR was defined as the percentage of participants who had a BOR of CR or PR or SD (minimum duration from randomization to SD greater than or equal to 7 weeks).
Assessments were performed every 8 weeks and were based on investigator review data using RECIST 1.1.
The 95% CI was constructed using the method of Clopper and Pearson.
DCR = CR + PR + SD greater than or equal to 7 weeks.
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Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
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Durable Stable Disease (SD) Rate
Lasso di tempo: Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
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The durable SD rate was defined as the percentage of participants whose BOR was SD and the duration of SD was greater than or equal to 23 weeks.
The durable SD was based on investigator review data using RECIST 1.1.
The 95% CI was constructed using the method of Clopper and Pearson.
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Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
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Clinical Benefit Rate (CBR)
Lasso di tempo: Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
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The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (duration of SD was greater than or equal to 23 weeks) and was based on investigator review data using RECIST 1.1.
The BOR was defined as the best response recorded from the start of study treatment until discontinuation from the study.
There was no requirement for confirmatory measurement of PR or CR to deem either one the BOR.
The 95% CI was constructed using the method of Clopper and Pearson.
CBR = CR + PR + SD greater than or equal to 23 weeks.
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Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
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Summary of Plasma Concentrations of Lenvatinib for Sparse Pharmacokinetic (PK) Sampling for Phase 1b and Phase 2
Lasso di tempo: Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
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Blood samples were collected during the Randomization Phase.
Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose).
Plasma concentrations of lenvatinib were measured and concentration data were summarized.
The summary statistics at time points with one or more below the limit of quantitation (BLQ) values were calculated by assigning zero for each BLQ value.
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Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
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Summary of Blood Concentrations of Everolimus for Sparse PK Sampling for Phase 1b and Phase 2
Lasso di tempo: Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
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Blood samples were collected during the Randomization Phase.
Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose).
Whole blood concentrations of everolimus were measured and concentration data were summarized.
The summary statistics at time points with one or more BLQ values were calculated by assigning zero for each BLQ value.
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Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
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Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC(0-24)) for Lenvatinib When Administered Alone or in Combination With Everolimus
Lasso di tempo: Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
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Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling.
Blood samples were analyzed for study drug using standardized methods.
PK parameters for lenvatinib were derived from lenvatinib concentration data using non-compartmental methods.
Data were compared via descriptive statistics between single agent and combination therapy.
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Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
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Maximum Concentration (Cmax) of Lenvatinib in Plasma When Administered Alone or in Combination With Everolimus
Lasso di tempo: Phase 2: Cycle 1 Day 15
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Cmax for lenvatinib was defined as the maximum observed concentration of lenvatinib in plasma following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured plasma concentration-time curves.
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Phase 2: Cycle 1 Day 15
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Time to Cmax (Tmax) for Lenvatinib When Administered Alone or in Combination With Everolimus
Lasso di tempo: Phase 2: Cycle 1 Day 15
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Tmax for lenvatinib was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach maximum concentration (Cmax) of lenvatinib in plasma.
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Phase 2: Cycle 1 Day 15
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Area Under the Blood Concentration-Time Curve From 0 to 24 Hours for Everolimus When Administered Alone or in Combination With Lenvatinib
Lasso di tempo: Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
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Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling.
Blood samples were analyzed for study drug using standardized methods.
PK parameters for everolimus were derived from everolimus concentration data using non-compartmental methods.
Data were compared via descriptive statistics between single agent and combination therapy.
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Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
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Maximum Concentration of Everolimus (Cmax) in Blood When Administered Alone or in Combination With Lenvatinib
Lasso di tempo: Phase 2: Cycle 1 Day 15
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Cmax for everolimus was defined as the maximum observed concentration of everolimus in blood following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured blood concentration-time curves.
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Phase 2: Cycle 1 Day 15
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Time to Cmax (Tmax) for Everolimus When Administered Alone or in Combination With Lenvatinib
Lasso di tempo: Phase 2: Cycle 1 Day 15
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Tmax for everolimus was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach the maximum concentration (Cmax) of everolimus in blood.
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Phase 2: Cycle 1 Day 15
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- Lee CH, Motzer RJ, Glen H, Michaelson MD, Larkin J, Minoshima Y, Kanekiyo M, Ikezawa H, Sachdev P, Dutcus CE, Funahashi Y, Voss MH. Correlative serum biomarker analyses in the phase 2 trial of lenvatinib-plus-everolimus in patients with metastatic renal cell carcinoma. Br J Cancer. 2021 Jan;124(1):237-246. doi: 10.1038/s41416-020-01092-0. Epub 2020 Oct 7.
- Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-1482. doi: 10.1016/S1470-2045(15)00290-9. Epub 2015 Oct 22. Erratum In: Lancet Oncol. 2016 Jul;17 (7):e270. Lancet Oncol. 2018 Oct;19(10):e509.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
5 agosto 2010
Completamento primario (Effettivo)
13 giugno 2014
Completamento dello studio (Effettivo)
8 febbraio 2018
Date di iscrizione allo studio
Primo inviato
26 maggio 2010
Primo inviato che soddisfa i criteri di controllo qualità
2 giugno 2010
Primo Inserito (Stima)
3 giugno 2010
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
27 febbraio 2019
Ultimo aggiornamento inviato che soddisfa i criteri QC
7 febbraio 2019
Ultimo verificato
1 gennaio 2018
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Neoplasie per tipo istologico
- Neoplasie
- Neoplasie urologiche
- Neoplasie urogenitali
- Neoplasie per sede
- Malattie renali
- Malattie urologiche
- Adenocarcinoma
- Neoplasie, ghiandolari ed epiteliali
- Neoplasie renali
- Carcinoma, cellule renali
- Carcinoma
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Inibitori enzimatici
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Inibitori della chinasi proteica
- Everolimo
- Lenvatinib
Altri numeri di identificazione dello studio
- E7080-G000-205
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Carcinoma a cellule renali metastatico
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National Cancer Institute (NCI)NCIC Clinical Trials Group; Southwest Oncology Group; Cancer and Leukemia Group BCompletatoCarcinoma a cellule renali a cellule chiare | Cancro a cellule renali in stadio III AJCC v7 | Cancro a cellule renali in stadio II AJCC v7 | Stadio I Renal Cell Cancer AJCC v6 e v7Stati Uniti, Canada, Porto Rico
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National Cancer Institute (NCI)TerminatoCarcinoma a cellule renali a cellule chiare | Carcinoma a cellule renali metastatico | Cancro a cellule renali in stadio III AJCC v7 | Cancro a cellule renali in stadio IV AJCC v7 | Cancro a cellule renali in stadio II AJCC v7 | Stadio I Renal Cell Cancer AJCC v6 e v7Stati Uniti
Prove cliniche su Lenvatinib
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Memorial Sloan Kettering Cancer CenterCompletatoCancro testa e collo | Carcinoma a cellule squamose della testa e del collo | Carcinoma della testa e del collo | Carcinoma cutaneo a cellule squamoseStati Uniti
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Shanghai Junshi Bioscience Co., Ltd.Attivo, non reclutanteCarcinoma epatocellulare avanzato (HCC)Italia, Polonia, Singapore, Stati Uniti, Cina, Ucraina
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Regina Elena Cancer InstituteUniversity of Pisa; University of Roma La Sapienza; University of Turin, Italy; Istituto... e altri collaboratoriReclutamentoCarcinoma tiroideo differenziato | GenereItalia
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Shandong New Time Pharmaceutical Co., LTDReclutamentoCarcinoma epatocellulareCina
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CStone PharmaceuticalsAttivo, non reclutanteCarcinoma epatocellulareSpagna, Cina, Stati Uniti, Polonia, Italia, Taiwan
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Cancer Institute and Hospital, Chinese Academy...Attivo, non reclutanteCarcinoma epatocellulare | Radioterapia | LenvatinibCina
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Shanghai Zhongshan HospitalAttivo, non reclutanteColangiocarcinoma, intraepaticoCina
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Peking Union Medical College HospitalCompletatoColangiocarcinoma | Biomarcatore | Immunoterapia combinata | Neoplasia epatica maligna primariaCina
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Tianjin Medical University Second HospitalReclutamento
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Peking Union Medical College HospitalSun Yat-Sen Memorial Hospital of Sun Yat-Sen University; The Second Affiliated...ReclutamentoCarcinoma ovarico ricorrenteCina