- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01056601
Panobinostat & Bortezomib in Pancreatic Cancer Progressing on Gemcitabine Therapy
December 3, 2017 updated by: Masonic Cancer Center, University of Minnesota
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
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
7
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- Masonic Cancer Center, University of Minnesota
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Pancreatic Cancer Patients
Pancreatic cancer patients who received treatment with bortezomib and panobinostat after progressing on gemcitabine.
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1.3 mg/m^2 administered intravenously twice daily on days 1 and 8 for 2 weeks followed by 10 day rest period
Other Names:
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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 1 Year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Up to 1 Year
|
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).
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Up to 1 Year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2010
Primary Completion (ACTUAL)
February 1, 2011
Study Completion (ACTUAL)
February 1, 2011
Study Registration Dates
First Submitted
January 25, 2010
First Submitted That Met QC Criteria
January 25, 2010
First Posted (ESTIMATE)
January 26, 2010
Study Record Updates
Last Update Posted (ACTUAL)
December 28, 2017
Last Update Submitted That Met QC Criteria
December 3, 2017
Last Verified
November 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Pancreatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Bortezomib
- Panobinostat
Other Study ID Numbers
- 2009LSUC012
- X05302 (OTHER: Millennium Pharmaceuticals, Inc.)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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