Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma|
- Safety [ Time Frame: Continuous ]
- Maximum Tolerated Dose (MTD) [ Time Frame: Continuous ]
- Pharmacokinetics [ Time Frame: Continuous ]
- Pharmacodynamics [ Time Frame: Continuous ]
- Response [ Time Frame: Continous ]
|Study Start Date:||May 2006|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Advanced Solid Tumor Malignancies and Refractory Lymphoma
NPI-0052 IV injection at doses ranging from 0.0125 to 0.8 mg/m2 over 1 to 10 minutes on Day 1, Day 8, Day 15 of each 28-day Cycle; 11 dose cohorts during dose-escalation
NPI-0052 (also known as marizomab) is a second generation proteasome inhibitor being developed as an anticancer agent. Proteasomes are responsible for degrading substrates such as damaged and aged proteins, tumor suppressors, and cell cycle regulators, and for regulating NF-κB activation by degrading its inhibitor, IκB. Blocking the proteasome pathway results in accumulation of proteins, which can cause cell death, particularly in tumor cells (Kisselev, 2001).
The Food and Drug Administration (FDA) approved the first proteasome inhibitor (bortezomib; Velcade®) in 2003 for the treatment of patients with multiple myeloma (MM) and subsequently for treatment of patients with mantle cell lymphoma in 2006. Although this compound has demonstrated efficacy in both of those indications, resistance and toxicity develop with continued therapy. Resistance may result from a variety of mechanisms. Bortezomib toxicity (primarily neurological with peripheral neuropathy and neuralgia, and also thrombocytopenia and neutropenia) can result in treatment discontinuation (about 25% of patients in a clinical trial conducted in patients at time of first relapse required cessation of therapy due to adverse events).
NPI-0052 inhibits the chymotrypsin-like (CT-L), caspase-like (C-L), and trypsin-like (T-L) activity of human erythrocyte-derived 20S proteasomes. Also known as salinosporamide A, NPI-0052 is a novel chemical entity discovered during the fermentation of Salinispora tropica NPS021184, a marine actinomycete, and is manufactured by saline fermentation. NPI-0052 was shown in nonclinical studies to have increased potency and duration of biological effects compared with bortezomib and may provide a significant therapeutic advantage, particularly if toxicity is less at therapeutic doses.
This was the first-in-human study of NPI-0052, and was conducted in cancer patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00396864
|United States, Arizona|
|Premiere Oncology of America|
|Scottsdale, Arizona, United States, 85260|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|United States, Texas|
|Univ. of Texas MD Anderson Cancer Center|
|Houston,, Texas, United States, 77030|
|Study Director:||Steven D Reich, MD||Triphase Research and Development I Corp|