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- Klinische proef 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
Studie Overzicht
Toestand
Interventie / Behandeling
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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Florida
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Tampa, Florida, Verenigde Staten, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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).
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Sequentiële toewijzing
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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.
Andere namen:
1A: Begins Day 1. Level 1 - 30 mg, Level 2 - 40 mg, Level 3 - 40 mg.
Andere namen:
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.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Maximum Tolerated Dose (MTD) of Afatinib (BIBW 2992) in Combination With Dasatinib
Tijdsspanne: Up to 6 Months
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The MTD for this combined treatment will be defined as either:
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Up to 6 Months
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Number of Participants With Objective Response
Tijdsspanne: Up to 6 Months
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Estimates objective response rate (complete response [CR] and partial response [PR]) in participants with acquired EGFR resistance
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Up to 6 Months
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Median Progression Free Survival
Tijdsspanne: Up to 6 Months
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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.
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Up to 6 Months
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Medewerkers en onderzoekers
Onderzoekers
- Hoofdonderzoeker: Ben Creelan, M.D., H. Lee Moffitt Cancer Center and Research Institute
Publicaties en nuttige links
Nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
- Ziekten van de luchtwegen
- Neoplasmata
- Niet-kleincellige longkanker
- Longziekten
- Thoracale neoplasmata
- Dasatinib
- EGFR-mutatie
- Tyrosinekinaseremmers
- Neoplasmata per site
- Afatinib
- Borstvliesuitstroming
- Longneoplasmata
- Carcinoom, bronchogeen
- Neoplasmata van de luchtwegen
- Epidermale groeifactorreceptor (EGFR)
- Pleurale neoplasmata
- Pleurale effusie, kwaadaardig
- Pleurale ziekten
- Genmutatie
- T790M mutation.
Aanvullende relevante MeSH-voorwaarden
- Ziekten van de luchtwegen
- Neoplasmata
- Longziekten
- Neoplasmata per site
- Neoplasmata van de luchtwegen
- Thoracale neoplasmata
- Carcinoom, bronchogeen
- Bronchiale neoplasmata
- Longneoplasmata
- Carcinoom, niet-kleincellige long
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antineoplastische middelen
- Proteïnekinaseremmers
- Afatinib
- Dasatinib
Andere studie-ID-nummers
- MCC-17176
- BI 1200.166 (Andere identificatie: Boehringer Ingelheim)
- BMS CA180-379 (Andere identificatie: Bristol-Myers Squibb)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
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