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Carboplatin and Paclitaxel With or Without Vorinostat in Treating Patients With Advanced Non-Small Cell Lung Cancer

22 luglio 2015 aggiornato da: National Cancer Institute (NCI)

Phase II Randomized Study of Vorinostat or Placebo in Combination With Carboplatin and Paclitaxel for Patients With Advanced Non-small Cell Lung Cancer

Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving carboplatin and paclitaxel together is more effective with or without vorinostat in treating non-small cell lung cancer.

Panoramica dello studio

Descrizione dettagliata

PRIMARY OBJECTIVES:

I. To compare progression-free survival associated with the combination of carboplatin, paclitaxel and vorinostat versus carboplatin, paclitaxel and placebo for patients with previously untreated, advanced NSCLC.

SECONDARY OBJECTIVES:

I. To determine the response rate, time to treatment failure, and overall survival for the two regimens.

II. To assess the safety profile of the regimen of vorinostat, carboplatin and paclitaxel for patients with advanced NSCLC.

III. To understand the mechanistic aspects of drug effect by conducting correlative science studies on peripheral blood and archived tumor tissue.

An initial safety run-in study is planned (phase I) before starting the phase II randomized study as described below. Doses of Vorinostat to be tested during the safety run-in portion are: Dose Level -1 500 mg QD, Dose Level 1 600 mg QD, Dose Level 2 800 mg QD. Patients will not be randomized during the safety lead-in period, and no patients treated during the lead-in will be considered in the primary evaluation of each arm in any comparison. Once the safety run-in portion is completed, all patients will randomized to receive either placebo or vorinostat at a fixed dose determined during the run-in portion.

Phase II Portion of Study:

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat orally (PO) once daily on days -2 to 2.

ARM II: Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.

In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, quarterly for 1 year, and then twice a year thereafter.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

23

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

    • California
      • Duarte, California, Stati Uniti, 91010
        • City of Hope Medical Center
      • Duarte, California, Stati Uniti, 91010
        • City of Hope Comprehensive Cancer Center
      • Los Angeles, California, Stati Uniti, 90033
        • USC / Norris Comprehensive Cancer Center
      • Sacramento, California, Stati Uniti, 95817
        • University of California Davis Comprehensive Cancer Center
    • Florida
      • Tampa, Florida, Stati Uniti, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30322
        • Emory University/Winship Cancer Institute
    • Illinois
      • Peoria, Illinois, Stati Uniti, 61615
        • Illinois CancerCare-Peoria
      • Springfield, Illinois, Stati Uniti, 62794
        • Southern Illinois University School of Medicine - Obstetrics and Oncology
    • Missouri
      • Saint Louis, Missouri, Stati Uniti, 63141
        • Saint John's Mercy Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, Stati Uniti, 27599
        • University of North Carolina
    • Pennsylvania
      • Hershey, Pennsylvania, Stati Uniti, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Pittsburgh, Pennsylvania, Stati Uniti, 15232
        • University of Pittsburgh
      • Pittsburgh, Pennsylvania, Stati Uniti, 15232
        • University of Pittsburgh Cancer Institute
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37232
        • Vanderbilt-Ingram Cancer Center
    • Virginia
      • Richmond, Virginia, Stati Uniti, 23298
        • Virginia Commonwealth University/Massey Cancer Center

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

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Patients must have histologically confirmed non-small cell lung cancer
  • No prior chemotherapy for advanced or metastatic disease
  • ECOG performance status 0 or 1
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
  • Life expectancy of greater than 12 weeks
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy in a metastatic setting
  • Patients may not be receiving any other investigational agents
  • Patients with untreated brain metastases should be excluded from this clinical trial; however, patients who have stable brain disease (should be off corticosteroids) at least 3 weeks after completion of appropriate therapy are eligible
  • Patients who have received any prior HDAC inhibitor (except valproic acid for seizure control provided that the valproic acid has been stopped at least 30 days before beginning therapy on this protocol) are excluded from this study
  • Peripheral neuropathy of severity greater than grade 1
  • Known history of allergic reactions to paclitaxel
  • Prior therapy with paclitaxel
  • Inability to take oral medications on a continuous basis; patients unable to swallow the vorinostat capsules whole are ineligible (the capsules cannot be crushed or broken)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with vorinostat; women of childbearing potential must use an appropriate double barrier method of birth control (such as female use of a diaphragm, intrauterine device [IUD], sponge and spermicide, in addition to the male use of a condom) or a prescribed birth control implant or practice abstinence; both double barrier contraception and implants must be used for at least one week prior to the start of the research study and continue for at least two weeks following the last study visit; please note that birth control pills should not be used while on this study as they may have a negative interaction with the experimental drug in this study
  • HIV-positive patients receiving combination antiretroviral therapy are 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: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Arm I (paclitaxel, carboplatin, vorinostat)
Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat PO once daily on days -2 to 2.
Studi correlati
Dato IV
Dato IV
Altri nomi:
  • Anzatax
  • IMPOSTA
Dato PO
Altri nomi:
  • SAHA
  • Suberoilanilide acido idrossamico
  • L-001079038
  • Acido suberaniloidrossiammico
Comparatore attivo: Arm II (paclitaxel, carboplatin, placebo)
Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.
Studi correlati
Dato IV
Dato PO
Altri nomi:
  • PLCB
Dato IV
Altri nomi:
  • Anzatax
  • IMPOSTA

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Progression-free Survival (PFS)
Lasso di tempo: From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 1 year

Estimated using the product-limit method of Kaplan and Meier.

PFS defined as time from randomization to progression or death due to any cause.

Progression defined as Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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.

From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 1 year

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Dose Limiting Toxicity (DLT) (Phase I)
Lasso di tempo: 4 weeks from start of treatment, up to 1 year
DLT is defined as any grade III or higher non-hematological toxicity except nausea, vomiting or alopecia. Nausea or vomiting (> grade 2) that last longer than 48 hours despite maximal medical therapy. Absolute neutrophil count < 1000/uL lasting longer than 7 days. Grade 4 thrombocytopenia (platelet < 25,000/uL). Grade 3 or 4 neutropenia associated with sepsis or fever > 38 C. Delay in starting cycle 2 by more than 2 weeks due to toxicity.Abnormal non-hematological laboratory criteria (Grade 3 or higher) will be considered a DLT, if clinically significant and drug-related. If baseline value is elevated prior to drug therapy, an increase will not be considered a DLT unless there is an elevation by more than 2 grades, and it is of clinical significance. Dose escalation schedule for vorinostat: 600 mg QD; 800 mg QD.
4 weeks from start of treatment, up to 1 year
Maximum Tolerated Dose (MTD) (Phase I)
Lasso di tempo: 4 weeks from start of treatment, up to 1 year
The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. The MTD is one dose level below the lowest dose in which 33% or more of the patients experience a DLT. The MTD is based on the first cycle of therapy. The recommended Phase II dose is generally the MTD, although secondary considerations of toxicity and dose reductions on subsequent cycles and other secondary considerations may result in the recommended Phase II dose being below the MTD.
4 weeks from start of treatment, up to 1 year

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Investigatori

  • Investigatore principale: Chandra Belani, MD, University of Pittsburgh

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 novembre 2010

Completamento primario (Effettivo)

1 aprile 2013

Completamento dello studio (Effettivo)

1 aprile 2013

Date di iscrizione allo studio

Primo inviato

5 agosto 2011

Primo inviato che soddisfa i criteri di controllo qualità

9 agosto 2011

Primo Inserito (Stima)

10 agosto 2011

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

18 agosto 2015

Ultimo aggiornamento inviato che soddisfa i criteri QC

22 luglio 2015

Ultimo verificato

1 settembre 2013

Maggiori informazioni

Termini relativi a questo studio

Altri numeri di identificazione dello studio

  • NCI-2010-02203 (Identificatore di registro: CTRP (Clinical Trial Reporting Program))
  • P30CA033572 (Sovvenzione/contratto NIH degli Stati Uniti)
  • U01CA099168 (Sovvenzione/contratto NIH degli Stati Uniti)
  • N01CM62209 (Sovvenzione/contratto NIH degli Stati Uniti)
  • N01CM00071 (Sovvenzione/contratto NIH degli Stati Uniti)
  • N01CM00038 (Sovvenzione/contratto NIH degli Stati Uniti)
  • N01CM00100 (Sovvenzione/contratto NIH degli Stati Uniti)
  • 8703 (CTEP)
  • PHII-102 (Altro identificatore: City of Hope Comprehensive Cancer Center)

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 .

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