Study of Panobinostat in Patients With Neuroendocrine Tumors

Official Title: “A Phase II Trial of Panobinostat in Patients With Neuroendocrine Tumors”

This summary will use Panobinostat (LBH589) in patients with neuroendocrine tumors to see how the patient's tumor responds to panobinostat. Additionally, this study will examine how long it takes neuroendocrine tumor patient's cancer to progress while taking the drug and examine the overall survival of patients using panobinostat. Also, the study will examine the toxicity and tolerability of panobinostat in the patient population. Finally, this study will look at the effect of panobinostat on Notch 1 signaling before and after treatment with panobinostat.

Intervention(s) in this Clinical Trial

• Drug: panobinostat (LBH589)
  • Panobinostat will be taken once daily at 20 mg three times a week (every Monday, Wednesday, Friday). It will be taken as long as patients are benefiting from treatment.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: panobinostat
  • This is a single arm trial. All patients will take panobinostat

Primary Measures

• This study will measure the tumor response rate of patients with gastrointestinal neuroendocrine tumors using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  • Time Frame: every 8 weeks
    Safety Issue?: No

Secondary Measures

• Evaluate the toxicity an tolerability of panobinostat in the patient population
  • Time Frame: on a daily basis
    Safety Issue?: Yes
• Evaluate the time to progression and the overall survival of patients with gastrointestinal neuroendocrine tumors treated with panobinostat
  • Time Frame: on a daily basis
    Safety Issue?: No
• Delineate the expression of Notch 1 in neuroendocrine tumor samples before and during treatment with panobinostat
  • Time Frame: prior to treatment and prior to Cycle 3 of treatment
    Safety Issue?: No

Inclusion Criteria:

• Histologically confirmed, metastatic, low grade neuroendocrine neoplasms. Small cell lung cancers, paragangliomas, and pheochromocytomas are excluded
• Must have measurable disease as defined by RECIST
• 4 weeks from completion of major surgery, chemotherapy, or other systemic therapy or local liver therapy to study registration. Concurrent octreotide is allowed.
• Not allowed to be on concurrent chemotherapy or radiation
• 18 years of age or older
• ECOG Performance status of equal to or less than 2
• Able to sign and date a written informed consent prior to participation in the study
• Baseline MUGA or ECHO must demonstrate LVEF greater than or equal to the lower limit of the institutional normal
• Must have the following laboratory criteria: Neutrophil count greater than 1500/mm3, platelet count greater than 100,000/mm3L, hemoglobin greater than or equal to 9 g/dL, AST/SGOT and ALT/SGPT less than or equal to 2.5 x ULN, serum bilirubin less than or equal to 1.5 x ULN, serum creatinine less than or equal to 1.5 x ULN, total serum calcium greater than or equal to LLN, serum potassium greater than or equal to LLN, serum sodium greater than or equal to LLN, serum albumin greater than or equal to LLN or 3g/dl,
• Women of child bearing potential must have a negative urine pregnancy test within 72 hours of first administration of study treatment and must be willing to use two methods of contraception
• Patients with a history of hypertension must be well controlled (to less than 150/90 mmHg) on a stable regimen of anti-hypertensive therapy

Exclusion Criteria:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment
• Impaired cardiac function including any of the following: Screening ECG with a QTc greater than 450 msec, patients with congenital long QT syndrome, history of unsustained ventricular tachycardia, any history of ventricular fibrillation or torsades de pointes, bradycardia defined as heart rate less than 50 beats per minutes, patients with a myocardial infarction or unstable angina within 6 months of study entry, congestive heart failure, right bundle branch block or left anterior hemiblock
• Uncontrolled hypertension
• Unresolved diarrhea greater than CTCAE grade 1
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
• Other concurrent sever and/or uncontrolled medical conditions
• Patients with a history of another primary malignancy that, in the opinion of the investigator, would interfere with the assessment of the primary endpoint of the study
• Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C, baseline testing is not required
• Any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
• Any medication which may cause QTc prolongation or inducing torsades de pointes
• Use of concomitant medications that may interact with panobinostat

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of Wisconsin, Madison Other

Overall Clinical Trial Officials and Contacts

Noelle LoConte, MD Principal Investigator University of Wisconsin, Madison  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00985946

Study ID Number: 2010-0050 (CO08209)

ClinicalTrials.gov Identifier: NCT00985946

Health Authority: United States: Food and Drug Administration