- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00949325
Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma
8 marzo 2019 aggiornato da: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phase I/II Trial of Torisel and Liposomal Doxorubicin in Patients With Advanced Soft Tissue and Bone Sarcomas
The purpose of this study is to identify a safe dosing regimen for the combination of Torisel and liposomal doxorubicin in patients with recurrent sarcoma.
A secondary purpose of the study is to determine how effective this combination is for the treatment of recurrent sarcoma.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
The effectiveness of treatments for recurrent sarcomas is quite limited.
One hypothesis to explain the refractory nature of recurrent sarcomas is the existence of chemotherapy-resistant sarcoma stem cells.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
24
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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Maryland
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Baltimore, Maryland, Stati Uniti, 21231
- Johns Hopkins University
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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
1 anno e precedenti (Bambino, Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- Histologically confirmed sarcoma that is recurrent or refractory to conventional treatment
- Measurable disease by RECIST criteria
- ECOG (Eastern Cooperative Oncology Group) performance status < 2 (or Lansky/Karnofsky > 60% for children)
- Life expectancy greater than 3 months
- Adequate organ function
- absolute neutrophil count at least 1,500
- platelets at least 100,000
- bilirubin less than 1.5 x upper limit of normal
- AST (aspartate aminotransferase) and ALT(alanine aminotransferase) less than 2.5 x upper limit of normal
- creatinine less than 1.5 x upper limit of normal OR creatinine clearance at least 60 ml/min/1.73 m2
- fasting serum cholesterol less than 350
- fasting serum triglycerides less than 400
- PT (prothrombin) or INR (international normalized ratio) less than 1.3 x upper limit of normal
- normal urinalysis
- Ability to understand and sign the informed consent document
Exclusion Criteria:
- Prior chemotherapy or radiotherapy within 3 weeks of entering the study (6 weeks for nitrosoureas or mitomycin C)
- Prior treatment with a tyrosine kinase inhibitor within 10 days of entering the study
- History of pulmonary hypertension or pneumonitis
- Patients may not be receiving other investigational agents
- Prior therapy with rapamycin, rapamycin analogues, or tacrolimus
- Uncontrolled brain metastases
- History of grade 3 or 4 hypersensitivity to macrolide antibiotics
- Concurrent treatment with immunosuppressive agents other than a stable (for more than 2 weeks) dose of corticosteroids
- Uncontrolled intercurrent illness
- Pregnancy or breast feeding
- HIV-positive patients on combination antiretroviral therapy
- Grade 3 or 4 proteinuria
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: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: temsirolimus plus liposomal doxorubicin
Single arm study: Dose escalation of temsirolimus plus constant dose of liposomal doxorubicin.
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Patients were treated with temsirolimus (Torisel) weekly by IV and with liposomal doxorubicin (Doxil) (standard dose) by IV once every 28 days.
Cohorts of patients receive sequentially increasing dose of temsirolimus until dose limiting toxicity (DLT) occurred and the maximally tolerated dose (MTD) was identified.
The MTD dose was the standard dose of temsirolimus used for the remainder of the study.
Dose modifications were based on protocol parameters for toxicities.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Part 1: Incidence of Dose Limiting Toxicities
Lasso di tempo: End of second 28-day cycle
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Dose limiting toxicities in each dose cohort.
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End of second 28-day cycle
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Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Lasso di tempo: up to 5 years
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Number of days from day 1 of treatment until date of death from any cause.
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up to 5 years
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Lasso di tempo: up to 3 years
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Interval from Date of start of treatment to date of disease progression or death from any cause.
Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions.
Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression.
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up to 3 years
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Objective Response Rate
Lasso di tempo: up to 5 years
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Number of participants who completed at least 2 treatment cycles with evidence of response.
Response is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
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up to 5 years
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Maximum Observed Plasma Concentration (Cmax)
Lasso di tempo: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS
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Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Area Under the Curve (AUC)
Lasso di tempo: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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AUC was calculated using a single compartment model.
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Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Drug Clearance
Lasso di tempo: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS.
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Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Lasso di tempo: up to 3 years
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Interval from start of treatment to disease progression or death from any cause.
Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions.
Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression
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up to 3 years
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Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Lasso di tempo: up to 5 years
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up to 5 years
|
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Time to Response
Lasso di tempo: up to 5 years
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Number of days after 2 cycles of treatment, until maximal response is observed.
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up to 5 years
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Duration of Response
Lasso di tempo: up to 5 years
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Number of days until documentation of disease progression or date of death from other cause
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up to 5 years
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Clinical Benefit Rate
Lasso di tempo: up to 5 years
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Number of days from documented improvement to disease progression.
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up to 5 years
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Collaboratori
Investigatori
- Investigatore principale: David M Loeb, MD, PhD, Sidney kimmel comprehensive cancer center at johns hopkins
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
- Thornton KA, Chen AR, Trucco MM, Shah P, Wilky BA, Gul N, Carrera-Haro MA, Ferreira MF, Shafique U, Powell JD, Meyer CF, Loeb DM. A dose-finding study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcoma. Int J Cancer. 2013 Aug 15;133(4):997-1005. doi: 10.1002/ijc.28083. Epub 2013 Mar 4.
- Trucco MM, Meyer CF, Thornton KA, Shah P, Chen AR, Wilky BA, Carrera-Haro MA, Boyer LC, Ferreira MF, Shafique U, Powell JD, Loeb DM. A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas. Clin Sarcoma Res. 2018 Nov 5;8:21. doi: 10.1186/s13569-018-0107-9. eCollection 2018.
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
1 settembre 2009
Completamento primario (Effettivo)
1 settembre 2012
Completamento dello studio (Effettivo)
1 settembre 2012
Date di iscrizione allo studio
Primo inviato
28 luglio 2009
Primo inviato che soddisfa i criteri di controllo qualità
29 luglio 2009
Primo Inserito (Stima)
30 luglio 2009
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
11 marzo 2019
Ultimo aggiornamento inviato che soddisfa i criteri QC
8 marzo 2019
Ultimo verificato
1 marzo 2019
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Neoplasie, Connettivo e Tessuto Molle
- Neoplasie per tipo istologico
- Neoplasie
- Sarcoma
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Inibitori enzimatici
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Inibitori della topoisomerasi II
- Inibitori della topoisomerasi
- Agenti antibatterici
- Antibiotici, Antineoplastici
- Agenti antimicotici
- Doxorubicina
- Doxorubicina liposomiale
- Sirolimo
Altri numeri di identificazione dello studio
- J0963
- NA_00028490 (Altro identificatore: JHMI-IRB)
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 temsirolimus plus liposomal doxorubicin
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National Cancer Institute (NCI)Attivo, non reclutantePRETESTO I Epatoblastoma | PRETESTO II Epatoblastoma | PRETESTO III Epatoblastoma | PRETESTO IV EpatoblastomaStati Uniti, Canada, Porto Rico, Australia, Giappone, Brasile