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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NPI-0052 + Vorinostat Dose-Escalation | Experimental | 4 dose-escalation cohorts |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NPI-0052 (marizomib) + vorinostat | Drug | 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 |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven D Reich, MD | Triphase Research and Development I Corp | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Adelaide Hospital | Adelaide | South Australia | 5000 | Australia | ||
| The Queen Elizabeth Hospital |
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|
| To evaluate the anti-tumor activity of NPI-0052 and vorinostat | continuous |
| Woodville South |
| South Australia |
| 5011 |
| Australia |
| Sir Charles Gairdner Hospital and University of Western Australia | Nedlands | Western Australia | 6009 | Australia |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D010190 | Pancreatic Neoplasms |
| D008545 | Melanoma |
| D008223 | Lymphoma |
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004067 | Digestive System Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006474 | Hemorrhagic Disorders |
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| ID | Term |
|---|---|
| C475865 | marizomib |
| D000077337 | Vorinostat |
| D061988 | Proteasome Inhibitors |
| D056572 | Histone Deacetylase Inhibitors |
| ID | Term |
|---|---|
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D011480 | Protease Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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