Ignite Creation Date:
2024-05-05 @ 5:07 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00396864
Status:
COMPLETED
Last Update Posted:
2017-11-22
First Post:
2006-11-06
Brief Title:
Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma
Sponsor:
Celgene
Organization:
Celgene
Study Overview
Official Title:
Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma
Status:
COMPLETED
Status Verified Date:
2017-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Multicenter open-label study of NPI-0052 in patients with advanced solid tumor malignancies or refractory lymphoma whose disease had progressed after treatment with standard approved therapies that included 2 stages The initial stage involved dose escalation to an MTD and determination of a recommended Phase 2 dose The second stage comprised an expansion cohort at the recommended Phase 2 dose
Detailed Description:
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None