Panobinostat and Sorafenib in Treating Patients With Liver Cancer That is Metastatic and/or Cannot Be Removed by Surgery

NCT00873002 | Terminated Phase 1 DMC

• 3 other identifiers: CASE6208P30CA043703CLBH589BUS23T
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Liver Cancer

Keywords

adult primary hepatocellular carcinoma; advanced adult primary liver cancer; recurrent adult primary liver cancer; localized unresectable adult primary liver cancer

Outcome Measures

Primary Outcomes (1)

• Assessment of Safety and Tolerability

  •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.

  6months to 1 year

Secondary Outcomes (4)

• Progression-free survival

  6mo 1 year

• Overall survival

  until death

• Response as assessed by RECIST

  every 42 days

• Adverse events and abnormal laboratory value severity as assessed by NCI CTCAE version 3.0

  weekly during treatment to 30 days after treatment

Study Arms (1)

LBH589

ACTIVE COMPARATOR

This study utilizes a sequential dose-escalation design to define the MTD of LBH589 when combined with standard doses of sorafenib.

Drug: panobinostat; Drug: sorafenib tosylate

Interventions

panobinostat DRUG

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

LBH589

sorafenib tosylate DRUG

400 mg PO BID

LBH589

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Related Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Panobinostat; Sorafenib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Richard Kim, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2009
• First Posted: April 1, 2009
• Study Start: March 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: June 1, 2010
• Last Updated: March 20, 2012

Record last verified: 2012-03

Locations

US (1)