Phase Ib Study of Gemcitabine Plus Cisplatin or Carboplatin Plus Dovitinib in Patients With Advanced Solid Tumors
Phase Ib Study of Dovitinib in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Plus Carboplatin in Patients With Advanced Solid Tumors
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Descrizione dettagliata
This is a phase Ib study of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. This study will utilize standard 3+3 dose escalation rules to define the recommended phase II dose. Dose escalation will proceed independently in the two cohorts (cisplatin cohort: gemcitabine + cisplatin + dovitinib; carboplatin cohort: gemcitabine + carboplatin + dovitinib). Patients will receive treatment for up to 6 cycles, in the absence of toxicity, until disease progression
Primary Objective:
To determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin.
Secondary Objectives:
- To determine the response rate to treatment as per Response Evaluation Criteria in Solid Tumors (RECIST)
- To determine the toxicity of treatment at per the Common Terminology for Adverse Events (CTCAE v4)
- To determine the pharmacokinetics of dovitinib in combination with gemcitabine plus cisplatin or carboplatin.
Tipo di studio
Tipo di studio
Iscrizione (Effettivo)
Iscrizione
Fase
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
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New York
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New York, New York, Stati Uniti, 10029
- Icahn School of Medicine at Mount Sinai
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Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Written informed consent and HIPAA authorization for release of personal health information.
- Age ≥ 18 years at the time of consent.
- Karnofsky Performance Status of ≥ 70%.
- Advanced/metastatic solid tumor for which treatment with gemcitabine plus carboplatin or gemcitabine plus cisplatin would otherwise be warranted.
- Prior treatment with chemotherapy is permitted. Patients must not have received more than three prior chemotherapeutic regimens.
Adequate organ function as determined by the following laboratory values:
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 100 x 109/L
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Creatinine of ≤ 1.5 OR Calculated creatinine clearance of ≥ 60 cc/min for the cisplatin cohort.
Calculated creatinine clearance of ≥ 30 cc/min for the carboplatin cohort.
- Bilirubin ≤ 1.5 x ULN
- Aspartate aminotransferase (AST, SGOT) ≤ 1.5 ULN
- Alanine Aminotransferase (ALT, SGPT) < 1.5 ULN
- INR ≤ 1.5 and a PTT within normal limits
- LVEF assessed by 2-D echocardiogram (ECHO) > 50% or lower limit of normal or multiple gated acquisition scan (MUGA) > 45% or lower limit of normal
Exclusion Criteria:
- Prior treatment with more than three prior chemotherapy regimens.
- Has had major surgery within 30 days of starting the study treatment
- Have active CNS metastases.
- No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
- Prior cancer treatment must be completed at least 30 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxic effects of the regimen.
- Prior radiation therapy must be completed at least 30 days prior to being registered for protocol therapy.
- Pregnant or breastfeeding.
- Clinically significant infections as judged by the treating investigator.
- Impaired cardiac function or clinically significant cardiac diseases
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin
- Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception.
- Fertile males not willing to use contraception
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
|---|---|
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Comparatore attivo: Cisplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19.
Treatment will be recycled every 21-days.
The dose of dovitinib will be escalated in successive cohorts.
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Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19.
Treatment will be recycled every 21-days.
The dose of dovitinib will be escalated in successive cohorts
Altri nomi:
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Comparatore attivo: Carboplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19.
Treatment will be recycled every 21-days.
The dose of dovitinib will be escalated in successive cohorts.
|
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19.
Treatment will be recycled every 21-days.
The dose of dovitinib will be escalated in successive cohorts
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Recommended phase II dose of combination regimen
Lasso di tempo: Within the first 21 days of treatment
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The primary objectives of this study are to determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus carboplatin or cisplatin.
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Within the first 21 days of treatment
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Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Antitumor activity
Lasso di tempo: After every 2 cycles (42 days) of combination therapy up to 3 years
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A CT scan of the chest, abdomen, and pelvis will be performed after every 2 cycles (or sooner if there is evidence of disease progression) while on combination therapy until disease progression (eg, after cycle 2, after cycle 4, and after cycle 6).
Response to treatment will be determined using RECIST.
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After every 2 cycles (42 days) of combination therapy up to 3 years
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Collaboratori e investigatori
Sponsor
Sponsor
Collaboratori
Collaboratori
Investigatori
Investigatori
- Investigatore principale: Matthew D. Galsky, M.D., Icahn School of Medicine at Mount Sinai
Pubblicazioni e link utili
Pubblicazioni generali
- Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010 Feb;10(2):116-29. doi: 10.1038/nrc2780.
- Knowles MA. Novel therapeutic targets in bladder cancer: mutation and expression of FGF receptors. Future Oncol. 2008 Feb;4(1):71-83. doi: 10.2217/14796694.4.1.71.
- Sarker D, Molife R, Evans TR, Hardie M, Marriott C, Butzberger-Zimmerli P, Morrison R, Fox JA, Heise C, Louie S, Aziz N, Garzon F, Michelson G, Judson IR, Jadayel D, Braendle E, de Bono JS. A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin Cancer Res. 2008 Apr 1;14(7):2075-81. doi: 10.1158/1078-0432.CCR-07-1466.
Studiare le date dei record
Studia le date principali
Inizio studio
Inizio studio
Completamento primario (Effettivo)
Completamento primario
Completamento dello studio (Effettivo)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- GCO 11-0946
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