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NPI-0052 and Vorinostat in Patients With Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma

This study has been completed.
Information provided by (Responsible Party):
Triphase Research and Development I Corporation Identifier:
First received: April 22, 2008
Last updated: September 29, 2016
Last verified: September 2016
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
Multiple Myeloma
Drug: NPI-0052 (marizomib) + vorinostat
Phase 1

Study Type: Interventional
Study Design: 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:

Further study details as provided by Triphase Research and Development I Corporation:

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 ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetics and pharmacodynamics of NPI-0052 and vorinostat [ Time Frame: continuous ] [ Designated as safety issue: No ]
  • 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 ]

Enrollment: 22
Study Start Date: March 2008
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NPI-0052 + Vorinostat Dose-Escalation
4 dose-escalation cohorts
Drug: NPI-0052 (marizomib) + vorinostat

NPI-0052 IV injection over 1 to 10 minutes at doses ranging from 0.15 to 0.7 mg/m2 on Days 1, 8, and 15 of each 28-day Cycle

Oral vorinostat 300 mg was administered with food on Days 1 to 16 of each 28-day Cycle

Other Names:
  • marizomib
  • proteasome inhibitor
  • HDAC inhibitor
  • Zolinza


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Karnofsky Performance Status (KPS) at 70% or more.
  2. 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.
  3. 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).
  4. Adequate bone marrow, renal, liver function.
  5. Signed informed consent.

Exclusion Criteria:

  1. Recent administration of chemotherapy, biological, immunotherapy or investigational agent, major surgery, or radiotherapy.
  2. Intrathecal therapy.
  3. Known brain metastases.
  4. Significant cardiac disease.
  5. Prior treatment with vorinostat or NPI-0052, or other HDACi (including valproic acid) or proteasome inhibitors.
  6. Known allergy to any component of vorinostat. Prior hypersensitivity reaction of CTCAE Grade > 3 to therapy containing propylene glycol or ethanol.
  7. Pregnant or breast-feeding women.
  8. Concurrent, active secondary malignancy for which the patient is receiving therapy.
  9. Significant active infection.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00667082

Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia, 5011
Australia, Western Australia
Sir Charles Gairdner Hospital and University of Western Australia
Nedlands, Western Australia, Australia, 6009
Sponsors and Collaborators
Triphase Research and Development I Corporation
Study Director: Steven D Reich, MD Triphase Research and Development I Corp
  More Information

Responsible Party: Triphase Research and Development I Corporation Identifier: NCT00667082     History of Changes
Other Study ID Numbers: NPI-0052-103 
Study First Received: April 22, 2008
Last Updated: September 29, 2016
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Triphase Research and Development I Corporation:
Non small Cell Lung Cancer
Pancreatic Cancer
Multiple Myeloma

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Multiple Myeloma
Neoplasms, Plasma Cell
Pancreatic Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders processed this record on October 26, 2016