- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01999985
Phase I Trial of Afatinib (BIBW 2992) and Dasatinib in Non-small Cell Lung Cancer (NSCLC)
Phase I Trial Evaluating Safety and Tolerability of the Irreversible Epidermal Growth Factor Receptor Inhibitor Afatinib (BIBW 2992) in Combination With the SRC Kinase Inhibitor Dasatinib for Patients With Non-small Cell Lung Cancer (NSCLC)
The purpose of this study is to:
- Find out if the study drugs Afatinib and Dasatinib can be safely given together to patients with lung cancer
- Learn how these two drugs work in cancer cells when they are combined
- Learn more about the side effects of these two drugs when combined
- Find the highest doses of the study drugs Afatinib and Dasatinib that can be given safely without causing serious side effects
Studieöversikt
Status
Betingelser
Intervention / Behandling
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 1
Kontakter och platser
Studieorter
-
-
Florida
-
Tampa, Florida, Förenta staterna, 33612
- H. Lee Moffitt Cancer Center and Research Institute
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Pathologically or cytologically documented Stage IIIB/IV non-small cell lung cancer, or unresectable recurrent disease following locoregional treatment.
For Phase 1B Extension Only:
- Either or both of the following: A tumor which harbors an activating Epidermal Growth Factor Receptor (EGFR) - mutation; History of objective response, or stable disease for at least 6 months, after treatment with erlotinib, afatinib, or gefitinib.
- Either or both of the following: Progression or recurrence of disease after receiving prior continuous gefitinib, afatinib, or erlotinib; A tumor known to harbor a de novo T790M mutation, which is known to confer EGFR TKI resistance.
- Participants are allowed to have received systemic chemotherapy or investigational therapy in the intervening period prior to trial enrollment
- Capable of giving written informed consent.
- Evaluable disease, as follows: For Phase 1A Dose Escalation: Have the presence of any evaluable disease, including bone metastases, effusion, or cystic metastases. For Phase 1B Extension Only: Have progressive and measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1).
- Reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method during and for 3 to 6 months following the study.
- Participant agrees that IV bisphosphonates will be withheld during the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
- Have recovered from prior drug-related toxicity to Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE) v4, within 21 days of initiation of on-study treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at initial enrollment, as assessed by clinician or investigator.
Exclusion Criteria:
- Have previously completed or withdrawn from this study or any other study investigating dasatinib. Prior treatment with other tyrosine kinases, including afatinib, is acceptable.
- Prior recent systemic or investigational therapy within 21 days of initiation of study treatment. An exception is that epidermal growth factor receptor (EGFR) inhibitor may be continued up until 3 days of initiation of study treatment.
- Women who are pregnant or breastfeeding. Women of childbearing potential must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment.
- Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis and no longer require corticosteroids.
- Patients with disease progression in the central nervous system (CNS) only.
- Serious concomitant disorder, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the principal investigator).
- Uncorrected severe electrolyte disorder, including severe potassium (<3.0 mEq/L) or magnesium ( < 1.0 mEq/L) deficiency.
- Any gastrointestinal disorder with diarrhea as a major symptom, such as Crohn's, or pre-existing chronic diarrhea Common Toxicity Criteria (CTC) Grade ≥ 2 of any etiology. Included are malabsorption disorders that in the opinion of the study physician may affect absorption of either afatinib or dasatinib.
- Prior major surgery or radiation therapy within 14 days of initiation of treatment.
- Electrocardiogram (ECG) abnormalities indicative of arrhythmia (at the discretion of the investigator).
- History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to enrollment.
- Baseline (< 1 month before treatment) cardiac left ventricular function with resting ejection fraction of less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram.
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, congenital long QT syndrome, or Torsades de pointes).
- Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec for men and >480 msec for women per American College of Cardiology/American Heart Association [AHA/ACC] 2011 scientific statement).
- History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease).
- Patients currently taking drugs that are generally accepted to have a high risk of causing Torsades de Pointes.
- Patients with pre-existing interstitial lung disease (ILD), or pericardial / pleural effusion of grade 2 or higher. Trace pericardial or pleural effusion is acceptable.
- Patients who require chronic oxygen therapy for chronic obstructive pulmonary disease or pleural effusions (malignant or benign).
- Patients requiring comedication with potent P-gp inhibitors (including cyclosporin, azithromycin, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital salt with quinidine, ritonavir, valspodar, verapamil) or inducers (including rifampicin).
- Known active hepatitis B infection, known active hepatitis C infection, or known HIV carrier.
- Known or suspected active drug or alcohol abuse.
- Known hypersensitivity to afatinib, dasatinib, or the excipients of any of the trial drugs.
- Laboratory exclusion criteria: Absolute neutrophil count (ANC) < 1000 / mm^3, Platelet count < 100,000 / mm^3, Serum creatinine ≥1.5 times the upper normal limit or calculated/measured creatinine Clearance ≤60 mL/min., Total bilirubin ≥1.5 mg/dL (>26 mol/L, SI unit equivalent), Aspartate amino transferase (AST) or Alanine amino transferase (ALT) ≥ 2.5 times the upper limit of normal (if related to liver metastases ≥ five times the upper limit of normal).
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Sekventiell tilldelning
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: Dose Escalation and Dose Expansion
Dose escalation followed by dose expansion. Escalation cohort: Afatinib and Dasatinib. This study is divided into two parts. The first 8 - 18 people will be entered in the first part, called Phase 1A. Then this part will end. Expansion cohort:: Afatinib and Dasatinib. The next 20 people will enter into the second part, called Phase 1B. |
1A: Begins Day 8. Level 1 - 100 mg, Level 2 - 100 mg, Level 3 - 140 mg.
Andra namn:
1A: Begins Day 1. Level 1 - 30 mg, Level 2 - 40 mg, Level 3 - 40 mg.
Andra namn:
In Phase 1B, a mutationally selected 20 participants (total) will be treated at the recommended dose to confirm tolerability and evaluate for early response signal.
In Phase 1B, a mutationally selected 20 participants (total) will be treated at the recommended dose to confirm tolerability and evaluate for early response signal.
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Maximum Tolerated Dose (MTD) of Afatinib (BIBW 2992) in Combination With Dasatinib
Tidsram: Up to 6 Months
|
The MTD for this combined treatment will be defined as either:
|
Up to 6 Months
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Number of Participants With Objective Response
Tidsram: Up to 6 Months
|
Estimates objective response rate (complete response [CR] and partial response [PR]) in participants with acquired EGFR resistance
|
Up to 6 Months
|
Median Progression Free Survival
Tidsram: Up to 6 Months
|
Estimate the 6-month progression free survival (PFS) rate in participants with acquired EGFR resistance.
Response Criteria for Phase 1B will follow RECIST v.1.1:
Progressive Disease (PD) is defined as at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
|
Up to 6 Months
|
Samarbetspartners och utredare
Utredare
- Huvudutredare: Ben Creelan, M.D., H. Lee Moffitt Cancer Center and Research Institute
Publikationer och användbara länkar
Användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
- Luftvägssjukdomar
- Neoplasmer
- Icke-småcellig lungcancer
- Lungsjukdomar
- Thoracic neoplasmer
- Dasatinib
- EGFR-mutation
- Tyrosinkinashämmare
- Neoplasmer efter plats
- Afatinib
- Pleural effusion
- Lungneoplasmer
- Karcinom, bronkogent
- Neoplasmer i andningsvägarna
- Epidermal tillväxtfaktorreceptor (EGFR)
- Pleurala neoplasmer
- Pleural effusion, malign
- Pleurala sjukdomar
- Genmutation
- T790M mutation.
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
- Afatinib
- Dasatinib
Andra studie-ID-nummer
- MCC-17176
- BI 1200.166 (Annan identifierare: Boehringer Ingelheim)
- BMS CA180-379 (Annan identifierare: Bristol-Myers Squibb)
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 Lungcancer
-
Chang Gung Memorial HospitalAvslutad
-
University of ZurichDeep Breath Intelligence (DBI)RekryteringLung-/luftvägssjukdomarSchweiz
-
424 General Military HospitalAvslutad
-
Celularity IncorporatedAvslutadSteg 2 Lung sarkoidos | Steg 3 Lung sarkoidosFörenta staterna
-
Centre Hospitalier Universitaire, AmiensAvslutadHemodialyskomplikation | Lung ultraljudFrankrike
-
Tuberculosis Research Centre, IndiaInternational Union Against Tuberculosis and Lung Diseases; Sarvodaya Charitable... och andra samarbetspartnersAktiv, inte rekryterandePre-extensivt läkemedelsresistent lung-TB | Behandling Intolerant multiresistent lung-TB | Icke-responsiv multiresistent lung-TBIndien
-
Pontificia Universidad Catolica de ChileRekryteringLung ultraljud | Öppen bukkirurgiChile
-
University of Colorado, DenverChildren's Hospital Colorado; Food and Drug Administration (FDA)AvslutadHypertoni;Lung;PrimärFörenta staterna
-
University Hospital, LilleAvslutad
-
Papa Giovanni XXIII HospitalAvslutadLungtransplantation | Ex Vivo Lung PerfusionItalien
Kliniska prövningar på Dasatinib - 1A
-
Jiangsu Simcere Pharmaceutical Co., Ltd.RekryteringAvancerade eller metastaserande fasta tumörer med NTRK, ROS1 eller ALK genfusionKina
-
Stanford UniversityAvslutad
-
Bristol-Myers SquibbAvslutadFarmakokinetisk studie hos friska deltagareFörenta staterna
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Avslutad
-
BiogenAvslutad
-
Boryung Pharmaceutical Co., LtdAvslutadEssentiell hypertoni | Primär hyperkolesterolemiKorea, Republiken av
-
Hyoung Jin KangHar inte rekryterat ännuAkut lymfoblastisk leukemi, pediatrisk
-
Bristol-Myers SquibbAvslutadHepatit CArgentina, Australien, Belgien, Frankrike, Tyskland, Italien, Förenta staterna, Kanada, Spanien, Mexiko, Österrike, Polen, Nederländerna, Korea, Republiken av, Puerto Rico, Nya Zeeland, Finland, Grekland, Rumänien
-
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