Proteasome Inhibitor NPI-0052 and Vorinostat in Patients With Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma - Full Text View

Sponsor:	Nereus Pharmaceuticals, Inc.
Information provided by:	Nereus Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00667082

Purpose

This is a clinical trial examining the safety, pharmacokinetics, pharmacodynamics and efficacy of IV NPI-0052 (a proteasome inhibitor) in combination with oral vorinostat (Zolinza; a HDAC inhibitor) in patients with non-small cell lung cancer, pancreatic cancer, melanoma or lymphoma. Proteasome inhibitors block the breakdown of proteins by cells and HDAC inhibitors block modification of proteins regulating gene expression in cells. Both of these actions preferentially affect cancer cells, and the combination of the two has been seen to have a greater effect in laboratory studies.

Condition	Intervention	Phase
Non-small Cell Lung Cancer Pancreatic Cancer Melanoma Lymphoma	Drug: NPI-0052 + vorinostat	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label
Official Title:	NPI-0052 and Vorinostat in Patients With Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Lymphoma Melanoma Pancreatic Cancer

Drug Information available for: Suberoylanilide hydroxamic acid

U.S. FDA Resources

Further study details as provided by Nereus Pharmaceuticals, Inc.:

Primary Outcome Measures:

To determine the Maximum tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of the combination NPI-0052 and Vorinostat [ Time Frame: continuously ] [ Designated as safety issue: Yes ]
To evaluate the pharmacokinetics and pharmacodynamics of NPI-0052 and vorinostat [ Time Frame: continuous ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate the safety and toxicity profile of the combination of NPI-0052 and vorinostat [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
To evaluate the anti-tumor activity of NPI-0052 and vorinostat [ Time Frame: continuous ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	March 2008
Estimated Study Completion Date:	September 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: single arm study	Drug: NPI-0052 + vorinostat NPI-0052 IV weekly vorinostat oral daily Other Names: proteasome inhibitor HDAC inhibitor Zolinza

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Karnofsky Performance Status (KPS) at 70% or more.
Non-small cell lung cancer, pancreatic adenocarcinoma, melanoma or lymphoma for which a standard, approved therapy is not available. Patients must have lesions that are evaluable by RECIST criteria.
All Adverse Events of any prior chemotherapy, surgery, or radiotherapy, must have resolved to CTCAE (v. 3.0) Grade 1 or less(except for hemoglobin).
Adequate bone marrow, renal, liver function.
Signed informed consent.

Exclusion Criteria:

Recent administration of chemotherapy, biological, immunotherapy or investigational agent, major surgery, or radiotherapy.
Intrathecal therapy.
Known brain metastases.
Significant cardiac disease.
Prior treatment with vorinostat or NPI-0052, or other HDACi (including valproic acid) or proteasome inhibitors.
Known allergy to any component of vorinostat. Prior hypersensitivity reaction of CTCAE Grade > 3 to therapy containing propylene glycol or ethanol.
Pregnant or breast-feeding women.
Concurrent, active secondary malignancy for which the patient is receiving therapy.
Significant active infection.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667082

Contacts

Contact: Angie M Longenecker, RN

+1 858 200 8354

alongenecker@nereuspharm.com

Locations

Australia, South Australia
Royal Adelaide Hospital	Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Nancy Olszewski + 61 8 8222 4765 Nancy.olszewski@health.sa.gov.au
Principal Investigator: Michael Brown, MD
The Queen Elizabeth Hospital	Recruiting
Woodville South, South Australia, Australia, 5011
Contact: Louise Pirc + 61 8 8222 6410 louise.pirc@nwahs.sa.gov.au
Contact: Sue Yeend + 61 8 8222 6410 sue.yeend@nwahs.sa.gov.au
Principal Investigator: Timothy Price, MD/MBBS
Australia, Western Australia
Sir Charles Gairdner Hospital and University of Western Australia	Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Sharon Lobb, RN + 61 8 9346 1717 Sharon.Lobb@health.wa.gov.au
Contact: Judy Innes-Rowe, RN +61 8 9346 4520 Judy.Innes-Rowe@health.wa.gov.au
Principal Investigator: Michael Millward, MD

Sponsors and Collaborators

Nereus Pharmaceuticals, Inc.

Investigators

Study Director:

Matthew A Spear, MD

Nereus Pharmaceuticals, Chief Medical Officer

More Information

No publications provided

Responsible Party:	Angie Longenecker, RN, Nereus Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00667082 History of Changes
Other Study ID Numbers:	NPI-0052-103
Study First Received:	April 22, 2008
Last Updated:	June 22, 2010
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Nereus Pharmaceuticals, Inc.:

Non small Cell Lung Cancer
Pancreatic Cancer
Melanoma
Lymphoma

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Lymphoma
Melanoma
Pancreatic Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Vorinostat
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012