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

Phase 1

Completed

• Conditions: Non-Small Cell Lung Cancer; Pancreatic Cancer; Lymphoma; Melanoma; Multiple Myeloma
• Interventions: Drug: NPI-0052 (marizomib) + vorinostat

• Registration Number: NCT00667082
• Lead Sponsor: Celgene

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03
• Study First Submitted: 2008-04-22
• Study First Submitted QC: 2008-04-24
• Study First Posted: 2008-04-25
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-20
• Last Update Posted: 2017-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NPI-0052 + Vorinostat Dose-Escalation	NPI-0052 (marizomib) + vorinostat	4 dose-escalation cohorts

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
To evaluate the safety and toxicity profile of the combination of NPI-0052 and vorinostat	continuous
To evaluate the anti-tumor activity of NPI-0052 and vorinostat	continuous
To evaluate the pharmacokinetics and pharmacodynamics of NPI-0052 and vorinostat	continuous

Trial Locations

Locations (3)

The Queen Elizabeth Hospital; 🇦🇺 Woodville South, South Australia, Australia

Sir Charles Gairdner Hospital and University of Western Australia; 🇦🇺 Nedlands, Western Australia, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia