- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00787267
Phase II Study of Dasatinib in Previously Treated Patients With Advanced NSCLC (TOP0801)
Phase II Study of Dasatinib in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
On this study patients will receive dasatinib, a targeted therapy, for advanced NSCLC that has progressed after previous therapy. Safety and response to dasatinib will be assessed.
Fresh frozen tumor tissue must be available for genomics analysis prior to initiating dasatinib therapy. A biopsy must be obtained after any prior chemotherapy. If fresh frozen tumor tissue is not available, a biopsy will be required to participate in this trial.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
Lung cancer is the leading cause of cancer death in the United States. Twenty to seventy-five percent of patients initially treated with surgery or radiotherapy recur and become candidates for systemic therapy. Src expression has been identified in a majority of NSCLC cell lines and may be important in hypoxic growth and angiogenesis of NSCLC.
This phase II trial will investigate the activity of the oral Src inhibitor dasatinib in advanced stage NSCLC. We hypothesize that the inhibition of Src pathway with dasatinib will show anti-tumor activity in advanced NSCLC, with a tolerable safety profile.
Fresh frozen tissue is needed for the genomics analysis, thus a biopsy will be required to participate in this trial. The genomic analysis will determine if the tumor is Src-active or Src-inactive and responses to dasatinib compared. In stage I, 40 patients will be treated without prior knowledge of their tumoral Src-activity. If all stage I responses are observed in the Src-active patients, the second stage will only accrue that cohort. If all responses are observed in the Src-inactive cohort, the activity of dasatinib and genomic determination of dasatinib response will be re-evaluated. Otherwise, if during Stage I, responses are observed in both cohorts, they will be accrued separately and evaluated in a two-stage manner.
Dasatinib will be give orally twice daily and continue until progression of disease, intolerable toxicity or patient withdrawal. Imaging studies will be done pre-treatment then every 6 weeks to assess radiologic response to therapy.
Patients will be followed for 30 days after the last dose of dasatinib to assess toxicity.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
Kontakter och platser
Studieorter
-
-
North Carolina
-
Durham, North Carolina, Förenta staterna, 27710
- Duke University Medical Center
-
Durham, North Carolina, Förenta staterna, 27705
- Durham VA Medical Center
-
Raleigh, North Carolina, Förenta staterna, 27609
- Duke Raleigh
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Histological/cytological documented non-small cell lung cancer (NSCLC). Documentation of recurrence required if treated with surgical resection and/or external beam radiation therapy (XRT) with curative intent and now have recurrent disease.
- Fresh tissue biopsy material for genomics analysis prior to initiating dasatinib. If prior XRT, tissue biopsy must be outside XRT field. Biopsy must be after any prior chemotherapy.
Prior treatment (tx) to include one of the following:
- At least 1 prior systemic regimen (IV or oral agent) for Stage IV NSCLC or for recurrent disease.
- Recurrence within 12 months after completion of systemic neoadjuvant/adjuvant chemotherapy for early stage NSCLC.
- Combined modality platinum-based tx for Stage III NSCLC.
- Prior XRT permitted if ≥1 week since completion, XRT must be <25% of bone marrow reserve.
- At least one, non-radiated, measurable lesion (per RECIST).
- Age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) 0-2.
Adequate Organ Function:
- Total bilirubin < Upper limit normal (ULN)
- Hepatic enzymes (AST, ALT) ≤2.5x ULN
- Serum creatinine <1.5x ULN
- Hemoglobin ≥9 gm/dL
- Neutrophil count (ANC/AGC) ≥1500 per μL
- Platelets ≥100,000 per μL
- Prothrombin time (PT)/a Partial thromboplastin time (PTT) ≤1.5x control
- No other serious medical or psychiatric illness.
- Ability to take oral medication (dasatinib must be swallowed whole).
- Women of childbearing potential must have negative serum pregnancy test ≤72 hours and not >7 days prior to starting study drug.
- Sexually active males and females of reproductive potential must agree to use adequate method of contraception during tx and for at least 4 weeks after study drug stopped.
- Signed, written informed consent including Health Insurance Portability and Accountability Act (HIPAA) according to institutional guidelines.
Exclusion Criteria:
- Previous or concomitant malignancy in past 2 years other than curatively treated carcinoma in situ of cervix, or basal cell/squamous cell carcinoma of the skin.
- Prior tx with dasatinib or other agents that inhibit Src.
- Evidence of symptomatic pleural effusions (grade 2) unless undergo therapeutic thoracentesis as part of non-study care. Successful pleurodesis allowed. Patients who require supplemental oxygen or with oxygen saturation on room air <89% are not eligible. Pericardial effusions of any grade are not eligible.
- Untreated documented symptomatic central nervous system (CNS) metastases.
Cardiac Symptoms:
- Uncontrolled angina, congestive heart failure(CHF)or myocardial infarction within 6 months
- Diagnosed congenital long QT syndrome
- Any h/o clinically significant ventricular arrhythmias
- Prolonged QT corrected (QTc) interval on pre-entry EKG (>450 msec)
- Uncontrolled B/P as defined as >160/90 on B/P therapy
- Hypokalemia or hypomagnesaemia if it cannot be corrected.
- H/o diagnosed congenital acquired bleeding disorders.
- Ongoing or recent (≤3 months) significant (≥grade 3) GI bleeding.
Con Meds:
- Drugs having risk of causing Torsades de Pointes (must stop drug 7 days before dasatinib);
- Current therapeutic dose unfractionated heparin, low-molecular weight heparin, or coumadin therapy;
- St. John's Wort must be stopped while on dasatinib;
- IV bisphosphonates stopped 2 weeks pre/6 weeks post dasatinib.
- Prisoners/subjects compulsorily detained for tx of psychiatric and/or physical illness.
- Pregnant or breastfeeding.
- Active or uncontrolled infection requiring IV antibiotics.
- Impairment of GI function/disease that may alter absorption of dasatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- Received investigational drugs ≤4 weeks prior to starting study drug and/or not recovered from side effects of such therapy. Any other anti-neoplastic and/or molecular therapy must be discontinued 7 days prior to starting dasatinib.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: Dasatinib
After a biopsy is done to obtain fresh frozen tumor tissue (Stage I), dasatinib is to be administered as an oral dose of 70 mg twice daily on a continuous basis for 6 weeks. Every 6 weeks radiologic exam will be done to assess response. Treatment will continue until progression of disease, intolerable toxicity or patient withdrawal. For Stage II, a biopsy to obtain fresh frozen tumor tissue will also be done. Depending on results from Stage I and results of biopsy, treatment with dasatinib will be determined. |
70 mg PO twice daily until progression.
Re-assess radiographically every 6 weeks.
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Tumor Response
Tidsram: 2 years
|
Tumor response rate was defined by RECIST criteria: CR (complete response) = disappearance of all target lesions taking as reference the baseline sum of the longest diameter (LD); PR (partial response) = at least a 30% decrease in the sum of the longest diameter of target lesions; PD (progressive disease) = at least a 20% increase in the sum of the longest diameter of target lesions as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD (stable disease) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since the treatment started |
2 years
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Overall Survival
Tidsram: Progression and survival every 6 months
|
Overall survival (OS) is the duration from date of consent to date of death from any cause.
|
Progression and survival every 6 months
|
Grade 3-5 Toxicity Associated With Dasatinib Treatment
Tidsram: Duration of dasatinib treatment plus 30 days
|
Number of subjects with Grade 3-5 toxicity as assessed using NCI CTCAE criteria with the attribution of possibly, probably, or definitely related to protocol treatment.
|
Duration of dasatinib treatment plus 30 days
|
Describe Change in Serum Levels of C-terminal Cross-linked Collagen I Between Pre-treatment and 6 Weeks After Starting Dasatinib.
Tidsram: 2 years
|
2 years
|
|
Determine Relationship Between K-ras Gene Mutation and Response to Dasatinib.
Tidsram: 2 years
|
2 years
|
Samarbetspartners och utredare
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Michael Kelley, MD, Duke University
Publikationer och användbara länkar
Allmänna publikationer
Användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Luftvägssjukdomar
- Neoplasmer
- Lungsjukdomar
- Neoplasmer efter plats
- Neoplasmer i andningsvägarna
- Thoracic neoplasmer
- Karcinom, bronkogent
- Bronkiella neoplasmer
- Lungneoplasmer
- Karcinom, icke-småcellig lunga
- Molekylära mekanismer för farmakologisk verkan
- Enzyminhibitorer
- Antineoplastiska medel
- Proteinkinashämmare
- Dasatinib
Andra studie-ID-nummer
- Pro00008303
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Icke småcellig lungcancer
-
City of Hope Medical CenterNational Cancer Institute (NCI)Aktiv, inte rekryterandeRefraktärt mogen T-cell och NK-cell non-Hodgkin lymfom | Mogen T-cell och NK-cell non-Hodgkin lymfom | Återkommande moget T- och NK-cells non-Hodgkin-lymfom | Återkommande kutant T-cell non-Hodgkin lymfom | Refraktärt kutant T-cell non-Hodgkin lymfomFörenta staterna
-
Stanford UniversityNational Institutes of Health (NIH); AmgenAvslutadLymfom, icke-Hodgkin | Lymfom: Non-Hodgkin | Lymfom: Icke-Hodgkin perifer T-cell | Lymfom: Non-Hodgkin kutant lymfom | Lymfom: Non-Hodgkin Diffus Stor B-cell | Lymfom: Non-Hodgkin follikulära / indolenta B-cell | Lymfom: Non-Hodgkin Mantle Cell | Lymfom: Non-Hodgkin Marginal Zone | Lymfom: Non-Hodgkin...Förenta staterna
-
Novartis PharmaceuticalsAvslutadMelanom | Trippel negativ bröstcancer | Anaplastisk sköldkörtelcancer | Andra fasta tumörer | Non-small Sell Lung Cancer (NSCLC)Förenta staterna, Italien, Spanien, Ungern, Taiwan, Tyskland, Nederländerna, Frankrike, Norge, Polen, Thailand, Libanon, Kalkon, Kanada
-
National Cancer Institute (NCI)AvslutadÅterkommande kutant T-cell non-Hodgkin lymfom | Steg I Kutant T-cell non-Hodgkin lymfom | Steg II Kutant T-cell non-Hodgkin lymfomFörenta staterna
-
Walter HanelAktiv, inte rekryterandeÅterkommande mogna T-cell och NK-cell non-Hodgkin lymfom | Återkommande primärt kutant T-cells non-Hodgkin-lymfom | Refraktärt mogen T-cell och NK-cell non-Hodgkin lymfom | Refraktärt anaplastiskt storcelligt lymfom | T-cell non-Hodgkin lymfom | Refraktärt primärt kutant T-cells non-Hodgkin-lymfom och andra villkorFörenta staterna
-
John ReneauAktiv, inte rekryterandeÅterkommande T-cell non-Hodgkin lymfom | Återkommande primärt kutant T-cells non-Hodgkin-lymfom | Steg III kutant T-cell non-Hodgkin lymfom | Steg IV Kutant T-cell non-Hodgkin lymfom | Primärt kutant anaplastiskt storcelligt lymfom | Refraktärt primärt kutant T-cells non-Hodgkin-lymfom | Lymfomatoid... och andra villkorFörenta staterna
-
City of Hope Medical CenterNational Cancer Institute (NCI)AvslutadAnaplastiskt storcelligt lymfom | Återkommande mogna T-cell och NK-cell non-Hodgkin lymfom | Refraktärt mogen T-cell och NK-cell non-Hodgkin lymfomFörenta staterna
-
Mayo ClinicRekryteringIndolent B-cell non-Hodgkin lymfom | Återkommande indolent non-Hodgkin-lymfom | Refraktärt indolent non-Hodgkin-lymfom | Återkommande indolent B-cell non-Hodgkin lymfom | Refraktärt indolent B-cell non-Hodgkin lymfomFörenta staterna
-
National Cancer Institute (NCI)RekryteringRefraktärt B-cells non-Hodgkin-lymfom | Refraktärt T-cell non-Hodgkin lymfom | Återkommande B-cells non-Hodgkin lymfom | Återkommande transformerat non-Hodgkin-lymfom | Återkommande non-Hodgkin lymfom | Refraktärt non-Hodgkin lymfom | Återkommande T-cell non-Hodgkin lymfom | Återkommande primärt kutant... och andra villkorFörenta staterna
-
Peking University Cancer Hospital & InstituteNanjing Legend Biotech Co.RekryteringÅterfall av B-cell non-Hodgkin lymfom | Refraktärt B-cell non-Hodgkin lymfomKina
Kliniska prövningar på Dasatinib
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Avslutad
-
Bristol-Myers SquibbAvslutadFarmakokinetisk studie hos friska deltagareFörenta staterna
-
Hyoung Jin KangHar inte rekryterat ännuAkut lymfoblastisk leukemi, pediatrisk
-
Jonsson Comprehensive Cancer CenterBristol-Myers SquibbAvslutad
-
Peking University Cancer Hospital & InstituteOkändGastrointestinal stromal tumörKina
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)Avslutad
-
Kanto CML Study GroupOkändMyelogen leukemi, kronisk, kronisk fasJapan
-
National Cancer Institute (NCI)NRG OncologyAvslutadÅterkommande fallopian Tube Carcinom | Återkommande äggstockscancer | Återkommande primärt peritonealt karcinom | Ovarialt klarcelligt cystadenocarcinom | Endometriellt klart cell adenokarcinom | Återkommande livmoderkroppscancerFörenta staterna
-
Xspray Pharma ABQPS Bioserve India Pvt LimitedAvslutad
-
National Cancer Institute (NCI)IndragenHematopoetisk och lymfoid cellneoplasma | Avancerat lymfom | Avancerad malignt fast neoplasma | Refraktärt lymfom | Eldfast malignt fast neoplasma | Refraktärt plasmacellsmyelomFörenta staterna