Panobinostat & Bortezomib in Pancreatic Cancer Progressing on Gemcitabine Therapy

NCT01056601 | Terminated Phase 2 Results DMC

• 2 other identifiers: 2009LSUC012X05302
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Keywords

insulinoma; cancer of pancreas; neoplasms, pancreas; alpha-cell tumor; glucagonoma; beta-cell tumor; somatostatinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Participants by Tumor Response

  Up to 1 Year

• Duration of Response

  Up to 1 Year

Study Arms (1)

Pancreatic Cancer Patients

EXPERIMENTAL

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

Drug: Bortezomib; Drug: Panobinostat

Interventions

Bortezomib DRUG

1.3 mg/m\^2 administered intravenously twice daily on days 1 and 8 for 2 weeks followed by 10 day rest period

Also known as: Velcade

Pancreatic Cancer Patients

Panobinostat DRUG

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

Also known as: LBH589

Pancreatic Cancer Patients

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• \> 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• Novartis Pharmaceuticals: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Insulinoma; Glucagonoma; Somatostatinoma

Interventions

Bortezomib; Panobinostat

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenoma, Islet Cell; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Islet Cell; Adenocarcinoma; Carcinoma; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Study was terminated early leading to small numbers of subjects analyzed; no solid conclusion can be derived.

Results Point of Contact

• Title: Arkaduisz Dudek, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

dudek002@umn.edu

612-624-0123

Study Officials

• Arkadiusz Dudek, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2010
• First Posted: January 26, 2010
• Study Start: September 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: December 28, 2017
• Results First Posted: August 26, 2011

Record last verified: 2017-11

Locations

US (1)