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

November 20, 2017 updated by: Celgene
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

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

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
      • Woodville South, South Australia, Australia, 5011
        • The Queen Elizabeth Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital and University of Western Australia

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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Zolinza
  • HDAC inhibitor
  • proteasome inhibitor
  • marizomib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the Maximum tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of the combination NPI-0052 and Vorinostat
Time Frame: continuously
continuously

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate the pharmacokinetics and pharmacodynamics of NPI-0052 and vorinostat
Time Frame: continuous
continuous
To evaluate the safety and toxicity profile of the combination of NPI-0052 and vorinostat
Time Frame: continuous
continuous
To evaluate the anti-tumor activity of NPI-0052 and vorinostat
Time Frame: continuous
continuous

Collaborators and Investigators

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

Sponsor

Celgene

Investigators

  • Study Director: Steven D Reich, MD, Triphase Research and Development I Corp

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

March 1, 2008

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

April 22, 2008

First Submitted That Met QC Criteria

April 24, 2008

First Posted (Estimate)

April 25, 2008

Study Record Updates

Last Update Posted (Actual)

November 22, 2017

Last Update Submitted That Met QC Criteria

November 20, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NPI-0052-103

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

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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