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- Klinische proef NCT00873002
Panobinostat and Sorafenib in Treating Patients With Liver Cancer That is Metastatic and/or Cannot Be Removed by Surgery
Phase I Study of Combination of Sorafenib and LBH589 in Hepatocellular Carcinoma
RATIONALE: Panobinostat and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of liver cancer by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with sorafenib in treating patients with liver cancer that is metastatic and/or cannot be removed by surgery.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
OBJECTIVES:
Primary
- Assess the safety and tolerability of panobinostat when combined with standard doses of sorafenib tosylate in patients with metastatic and/or unresectable hepatocellular carcinoma.
- Determine the maximum tolerated dose of panobinostat when combined with standard doses of sorafenib tosylate in these patients.
Secondary
- Determine the response rate.
- Determine the progression-free survival.
- Determine the overall survival rate.
OUTLINE: This is a dose escalation study of panobinostat.
Patients receive panobinostat IV on days 1 and 8 and oral sorafenib tosylate twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed for 30 days.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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Ohio
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Cleveland, Ohio, Verenigde Staten, 44195
- Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
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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
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed hepatocellular carcinoma
- Metastatic and/or unresectable disease
- Child-Pugh score A or B
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Neutrophil count > 1500/mm³
- Platelet count > 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if elevation due to disease involvement)
- Serum bilirubin ≤ 1.5 times ULN
- Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 50 mL/min
- Total serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal (LLN)
- Serum potassium ≥ LLN
- Serum sodium ≥ LLN
- Serum albumin ≥ LLN or 3 g/dL
- LVEF ≥ LLN as demonstrated by baseline MUGA or ECHO
- TSH and free T4 within normal limits (thyroid hormone replacement therapy allowed)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception (one being a barrier method) during and for 3 months after completion of study treatment
- INR < 1.5 or PT/PTT within normal limits
No impaired cardiac function including any 1 of the following:
- QTc > 450 msec on screening ECG
- Congenital long QT syndrome
- History of sustained ventricular tachycardia
- History of ventricular fibrillation or torsades de pointes
Bradycardia, defined as heart rate < 50 beats per minute
- Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible
- Myocardial infarction or unstable angina within the past 6 months
- Congestive heart failure (NYHA class III-IV)
- Right bundle branch block and left anterior hemiblock (bifascicular block)
- No uncontrolled hypertension
- No thrombolic or embolic events (e.g., cerebrovascular accident and transient ischemic attacks) within the past 6 months
- No pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within the past 4 weeks
- No other hemorrhage/bleeding event > CTCAE Grade 3 within the past 4 weeks
- No unresolved diarrhea > CTCAE grade 1
- No other concurrent severe and/or uncontrolled medical conditions
- No other primary malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
- No serious non-healing wound, ulcer, or bone fracture
- No evidence or history of bleeding diathesis or coagulopathy
- No significant traumatic injury within the past 4 weeks
- No known or suspected allergy to sorafenib tosylate or any other study drug
- No condition that would impair a patient's ability to swallow whole pills
- No malabsorption problem
- No known human immunodeficiency virus (HIV) or hepatitis C positivity (baseline testing for HIV and hepatitis C is not required)
- No significant history of non-compliance to medical regimens
PRIOR CONCURRENT THERAPY:
- No prior HDAC inhibitors, DAC inhibitors, HSP90 inhibitors, sorafenib tosylate, or valproic acid for the treatment of cancer
- More than 4 weeks since prior chemotherapy, investigational drugs, or major surgery and recovered
- More than 4 weeks since open biopsy
- More than 5 days since prior and no concurrent valproic acid for any medical condition
- No concurrent St. John's wort or rifampin
- No concurrent drugs with a risk of causing torsades de pointes
- No concurrent CYP3A4 inhibitors
- No concurrent radiotherapy
- No concurrent grapefruit, grapefruit juice, or Seville (sour) oranges
- No other concurrent investigational therapy
- No other concurrent anticancer agents
- Concurrent anticoagulation treatment with warfarin or heparin allowed
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
---|---|
Actieve vergelijker: LBH589
This study utilizes a sequential dose-escalation design to define the MTD of LBH589 when combined with standard doses of sorafenib.
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Dose escalation: 7.5 mg/m2 day 1 and day 8 of 21 days cycle 10 mg/m2 day 1 and day 8 of 21 days cycle 15 mg/m2 day 1 and day 8 of 21 days cycle 20 mg/m2 day 1 and day 8 of 21 days cycle 30 mg/m2 day 1 and day 8 of 21 days cycle
400 mg PO BID
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Assessment of Safety and Tolerability
Tijdsspanne: 6months to 1 year
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•Primary objective of the phase I trial will be to assess the safety and tolerability and to determine the maximum tolerated dose (MTD) of LBH 589 when combined with standard doses of sorafenib in the treatment of hepatocellular carcinoma.
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6months to 1 year
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Progression-free survival
Tijdsspanne: 6mo 1 year
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Evaluate time to progression vs progression free survival
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6mo 1 year
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Overall survival
Tijdsspanne: until death
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Overall survival (OS) will be measured from study entry until death from any cause.
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until death
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Response as assessed by RECIST
Tijdsspanne: every 42 days
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To ensure comparability, baseline methods and on-study methods for response assessment must be performed using identical techniques.
In addition, all subjects with evidence of objective tumor response (CR, PR or SD) should have the response confirmed with repeat assessments at least 21 days after the first documentation of response, resuming bimonthly (every 42 days) assessments thereafter.
Objective tumor response will be assessed using the RECIST method.
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every 42 days
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Adverse events and abnormal laboratory value severity as assessed by NCI CTCAE version 3.0
Tijdsspanne: weekly during treatment to 30 days after treatment
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Events should be documented and recorded at each visit.
Subjects should be followed for adverse events for 30 days after the last protocol related assessment, or until drug-related toxicities have resolved, whichever is later.
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weekly during treatment to 30 days after treatment
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Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Richard Kim, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start
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 (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Ziekten van het spijsverteringsstelsel
- Neoplasmata
- Neoplasmata per site
- Neoplasmata van het spijsverteringsstelsel
- Lever Ziekten
- Lever neoplasmata
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antineoplastische middelen
- Proteïnekinaseremmers
- Histondeacetylaseremmers
- Sorafenib
- Panobinostaat
Andere studie-ID-nummers
- CASE6208 (Andere identificatie: Case Comprehensive Cancer Center)
- P30CA043703 (Subsidie/contract van de Amerikaanse NIH)
- CLBH589BUS23T
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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