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

Study Overview
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Brief Summary
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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.

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

Conditions
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Non-Small Cell Lung Cancer, Pancreatic Cancer, Melanoma, Lymphoma, Multiple Myeloma

Intervention / Treatment
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* Drug: NPI-0052 (marizomib) + vorinostat


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPI-0052 + Vorinostat Dose-Escalation<br>4 dose-escalation cohorts | Drug: NPI-0052 (marizomib) + vorinostat<br>* 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<br>* Other names: Zolinza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the pharmacokinetics and pharmacodynamics of NPI-0052 and vorinostat |  | continuous | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non small Cell Lung Cancer, Pancreatic Cancer, Melanoma, Lymphoma, Multiple Myeloma