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Panobinostat & Bortezomib in Pancreatic Cancer Progressing on Gemcitabine Therapy

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ClinicalTrials.gov Identifier: NCT01056601
Recruitment Status : Terminated (Funding not available)
First Posted : January 26, 2010
Results First Posted : August 26, 2011
Last Update Posted : December 28, 2017
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE January 25, 2010
First Posted Date  ICMJE January 26, 2010
Results First Submitted Date  ICMJE July 28, 2011
Results First Posted Date  ICMJE August 26, 2011
Last Update Posted Date December 28, 2017
Study Start Date  ICMJE September 2010
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2011)
Progression-Free Survival [ Time Frame: Up to 1 Year ]
Median number of months before disease progressed in patient on gemcitabine when treated with the combination of panobinostat and bortezomib. Progression free survival is measured from randomization until the subject has documented disease progression by an objective measure. Subjects must be alive with no more than 20% increase in tumor size to qualify for progression free survival. Changes in tumor size are defined by RECIST criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: January 25, 2010)
Determine progression-free survival [ Time Frame: 3 months, 6 months, 1 year ]
Change History Complete list of historical versions of study NCT01056601 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2011)
  • Number of Participants by Tumor Response [ Time Frame: Up to 1 Year ]
    Number of patients whose tumor has responded to study therapy is determined using Response Evaluation Criteria In Solid Tumors. Progressive Disease (PD) is assessed if the sum of the diameters has increased by ≥ 20% and ≥ 5 mm from nadir (including baseline if it is the smallest sum). Objective response is measured by tumor reduction as defined in the RECIST criteria. Tumor shrinkage must be at least 30% to qualify as an objective response.
  • Duration of Response [ Time Frame: Up to 1 Year ]
    Duration of response is calculated as (Date of First Disease Progression or Death as a Result of any Cause whichever Comes First - Date of First Objective Status Assessment of Confirmed Complete or Partial Response as defined by RECIST criteria).
Original Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2010)
  • Determine tumor response rate [ Time Frame: 3 months, 6 months, 1 year ]
  • Determine duration of response [ Time Frame: 3 months, 6 months, 1 year ]
  • Characterize the quantitative and qualitative toxicities [ Time Frame: Day 1 through 30 days post treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Panobinostat & Bortezomib in Pancreatic Cancer Progressing on Gemcitabine Therapy
Official Title  ICMJE Phase II Study of Panobinostat (LBH589) Given in Combination With Bortezomib (Velcade) in Patients With Pancreatic Cancer Progressing on Gemcitabine Therapy Alone or Gemcitabine in Combination
Brief Summary Cancer results from multiple mutations which cause cells to grow uncontrolled. It therefore may be necessary to inhibit several oncogenic targets to affect cancer cell growth. Studies have shown that panobinostat (LH589) causes a wide range of effect on endothelial cells that lead to inhibition of tumor angiogenesis (a fundamental step in the transition of tumors from a dormant state to a malignant one). Bortezomib triggers cell death in pancreatic cancer cells but the mechanism is not well defined but has been determined to be cytostatic. Combining these two drugs may work together in the treatment of pancreatic cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • Drug: Bortezomib
    1.3 mg/m^2 administered intravenously twice daily on days 1 and 8 for 2 weeks followed by 10 day rest period
    Other Name: Velcade
  • Drug: Panobinostat
    20 milligrams administered orally 3 times weekly for 2 weeks on Days 1,3,5,8,10 and 12 followed by 9 day rest period
    Other Name: LBH589
Study Arms  ICMJE Experimental: Pancreatic Cancer Patients
Pancreatic cancer patients who received treatment with bortezomib and panobinostat after progressing on gemcitabine.
Interventions:
  • Drug: Bortezomib
  • Drug: Panobinostat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 28, 2011)
7
Original Estimated Enrollment  ICMJE
 (submitted: January 25, 2010)
65
Actual Study Completion Date  ICMJE February 2011
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histological diagnosis of locally advanced or metastatic pancreatic cancer (except neuroendocrine tumors, but including ampullary cancer) with progression after standard first line therapy that included gemcitabine (single agent or combination)
  • Measurable disease on computated tomography (CT) scan per Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • At least 28 days from previous systemic therapy, including investigational agents and 1st dose of study treatment and recovered from any acute toxic effects of that treatment before study enrollment.
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 - Ability to provide written consent
  • Must meet hematology and biochemistry laboratory criteria within 14 days of study enrollment:

    • Neutrophil count >1500/mm^3
    • Platelet count >100,000/mm^L
    • Hemoglobin > or = 9 g/dL
    • Aspartate aminotransferase (AST/SGOT) or Alanine transaminase (ALT/SGPT) < or = 2.5 times upper limit of normal (ULN)or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
    • Serum bilirubin < or = 1.5 x ULN
    • Serum creatinine < or = 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
    • Total serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal (LLN)
    • Serum phosphorus > or = LLN
    • Serum potassium > or = LLN
    • Serum sodium ≥ LLN
    • Serum magnesium ≥ LLN
    • Serum albumin ≥ LLN or 3g/dl
    • Patients with any elevated Alkaline Phosphatase due to bone metastasis can be enrolled
  • Baseline multi gated acquisition scan (MUGA) or echocardiogram (ECHO) must demonstration left ventricular ejection fraction (LVEF) > or = 50%
  • Normal thyroid function within normal limits. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
  • Women of childbearing potential (WOCBP) must have a negative pregnancy tests within 7 days of study treatment administration and willing to use 2 methods of contraception

Exclusion Criteria:

  • > 1 prior systemic treatment regimen for pancreatic cancer
  • Prior histone deacetylase (HDAC), deacetylase (DAC), heat shock protein 90 (HSP90) inhibitors or valproic acid for treatment of cancer
  • Anyone needing valproic acid for any medical condition during the study or 5 days prior to panobinostat treatment
  • Impaired cardiac function

    • Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (<50 beats per minute), QTcF > 450 msec on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block)
    • Presence of atrial fibrillation (ventricular heart rate >100 bpm)
    • Previous history angina pectoris or acute myocardial infarction (MI) within 6 months of study enrollment
    • Congestive heart failure (New York Heart Association functional classification III-IV) or baseline MUGA/Echo shows LVEF < 50%
  • Uncontrolled hypertension defined as hypertensive blood pressure of SBP > 140 or DBP > 90, despite antihypertensive medications
  • History of deep vein thrombosis (DVT), pulmonary emboli or other blood clotting abnormality within 3 months of study enrollment
  • Ongoing need for anti-coagulation therapy except daily low dose aspirin (≤ 100 mg/day) or low molecular weight heparin
  • Concomitant use of drugs with risk of causing torsades de pointes
  • Anyone with unresolved diarrhea > or = grade 2 at time of enrollment
  • Impairment of gastrointestinal function or disease that may significantly alter the absorption of panobinostat
  • Grade 2 or greater peripheral neuropathy within 14 days of enrollment
  • Serious concomitant medical or psychiatric disorders (e.g., active infection, uncontrolled diabetes)
  • Patients who have received chemotherapy, any investigational agent or undergone major surgery < 4 weeks prior to starting study drug
  • Male patients whose sexual partners are WOCBP and not using double method of contraception during the study and 3 months following.
  • Known positivity for human immunodeficiency virus (HIV) or hepatitis C
  • Hypersensitivity to bortezomib, boron or mannitol History of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01056601
Other Study ID Numbers  ICMJE 2009LSUC012
X05302 ( Other Identifier: Millennium Pharmaceuticals, Inc. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE
  • Novartis Pharmaceuticals
  • Millennium Pharmaceuticals, Inc.
Investigators  ICMJE
Principal Investigator: Arkadiusz Dudek, MD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP