Panobinostat & Bortezomib In Pancreatic Cancer Progressing On Gemcitabine Therapy

Study Overview

Panobinostat & Bortezomib in Pancreatic Cancer Progressing on Gemcitabine Therapy

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.

N/A

Pancreatic Cancer

DRUG: Bortezomib
DRUG: Panobinostat

2009LSUC012
X05302 (OTHER Identifier) (OTHER: Millennium Pharmaceuticals, Inc.)

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2010-01-25	Results First Submitted 2011-07-28	Last Update Submitted that met QC Criteria 2017-12-03
First Submitted that Met QC Criteria 2010-01-25	Results First Submitted that Met QC Criteria 2011-07-28	Last Update Posted (ACTUAL) 2017-12-28
First Posted (ACTUAL) 2010-01-26	Results First Posted 2011-08-26	Last Verified 2017-11

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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.	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 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

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Pancreatic Cancer Patients

Pancreatic cancer patients who received treatment with bortezomib and panobinostat after progressing on gemcitabine.

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

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

Primary Outcome Measures	Measure Description	Time Frame
Progression-Free Survival	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	Measure Description	Time Frame
Number of Participants by Tumor Response	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.	Up to 1 Year
Duration of Response	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).	Up to 1 Year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

> 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Novartis Pharmaceuticals
Millennium Pharmaceuticals, Inc.

Investigators

PRINCIPAL_INVESTIGATOR: Arkadiusz Dudek, MD, Masonic Cancer Center, University of Minnesota

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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