CancerPhase 1NCT00396864
Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma
A Phase 1 study testing NPI-0052 in people with Cancer and Lymphomas, run by Celgene at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- NPI-0052
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2006to Mar 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically-confirmed solid tumor malignancy (patients must be refractory to or demonstrate unacceptable toxicity towards effective therapy known to provide clinical benefit for their condition) OR refractory lymphoma (patients whose disease has progressed despite standard therapy including at least one-doxorubicin-containing regimen and one anti-CD20 monoclonal antibody-containing regimen.
- KPS ≥70%.
- All Adverse Events of any prior chemotherapy, surgery, or radiotherapy, must have resolved to NCI CTCAE (v. 3.0) Grade ≤ 1 (except for hemoglobin).
- Adequate bone marrow, renal, adrenal, pancreatic and liver function.
- Signed informed consent.
Who cannot join
- Administration of chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 28 days prior to receipt of study medication (6 weeks for nitrosoureas or mitomycin C; 12 weeks for radioimmunotherapy). Major surgery, other than diagnostic surgery, within 4 weeks before first study drug administration. Radiotherapy within 4 weeks.
- Patients that require G-CSF and/or platelet support.
- Patients with ongoing coagulopathies.
- Patients with prior bone marrow transplant therapy (autologous or allogeneic).
- Patients receiving intrathecal therapy.
- Known brain metastases.
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- Significant cardiac disease.
- Patients with a prior hypersensitivity reaction of CTCAE Grade ≥ 3 to therapy containing propylene glycol or ethanol.
- Pregnant or breast-feeding women. Female patients must be postmenopausal, surgically sterile or they must agree to use acceptable methods of birth control. Female patients with childbearing potential must have a negative serum pregnancy test. Male patients must be surgically sterile or agree to use an acceptable method of contraception.
- Concurrent, active secondary malignancy for which the patient is receiving therapy.
- Active uncontrolled bacterial or fungal infection requiring systemic therapy; infection requiring parenteral antibiotics.
- Known to be positive for HIV; active hepatitis A, B, or C infection.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Univ. of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Premiere Oncology of America
Scottsdale, Arizona, 85260
About this study
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.
Read the 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.
- Being tested
- NPI-0052
- Keywords
- cutaneous lymphoma, marginal zone lymphoma
- Medical subject headings
- Neoplasms, Lymphoma, Lymphoma, T-Cell, Cutaneous, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NPI-0052Drug
Also called Marizomib, MRZ
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
| Study group | Role | What they receive |
|---|---|---|
| NPI-0052 | Experimental | Advanced Solid Tumor Malignancies and Refractory Lymphoma Receives: Drug: NPI-0052 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Measured: Continuous
Maximum Tolerated Dose (MTD)
Measured: Continuous
Pharmacokinetics
Measured: Continuous
Secondary outcomes (2)
Pharmacodynamics
Measured: Continuous
Response
Measured: Continous
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2006 (estimated)
- Study startMay 2006
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Steven D Reich, MD, Study director, Triphase Research and Development I Corp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00396864
- Sponsor's protocol ID
- NPI-0052-100
- Status last verified
- Nov 2017
- First submitted
- 6 Nov 2006
- Last updated
- 22 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma
- ClinicalTrials.gov ID
- NCT00396864
- Acronym / sponsor ID
- NPI-0052-100
- Keywords
- cutaneous lymphoma, marginal zone lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 8 Nov 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NPI-0052 | Experimental | Drug: NPI-0052Advanced Solid Tumor Malignancies and Refractory Lymphoma |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically-confirmed solid tumor malignancy (patients must be refractory to or demonstrate unacceptable toxicity towards effective therapy known to provide clinical benefit for their condition) OR refractory lymphoma (patients whose disease has progressed despite standard therapy including at least one-doxorubicin-containing regimen and one anti-CD20 monoclonal antibody-containing regimen.
- KPS ≥70%.
- All Adverse Events of any prior chemotherapy, surgery, or radiotherapy, must have resolved to NCI CTCAE (v. 3.0) Grade ≤ 1 (except for hemoglobin).
- Adequate bone marrow, renal, adrenal, pancreatic and liver function.
- Signed informed consent.
Key exclusion criteria (12 listed)
- Administration of chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 28 days prior to receipt of study medication (6 weeks for nitrosoureas or mitomycin C; 12 weeks for radioimmunotherapy). Major surgery, other than diagnostic surgery, within 4 weeks before first study drug administration. Radiotherapy within 4 weeks.
- Patients that require G-CSF and/or platelet support.
- Patients with ongoing coagulopathies.
- Patients with prior bone marrow transplant therapy (autologous or allogeneic).
- Patients receiving intrathecal therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NPI-0052Also: Marizomib, MRZNPI-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 | Drug | NPI-0052 |
Primary outcome
Safety
Time frame: Continuous
Maximum Tolerated Dose (MTD)
Time frame: Continuous
Pharmacokinetics
Time frame: Continuous
2 secondary outcomes
Pharmacodynamics
Time frame: Continuous
Response
Time frame: Continous
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven D Reich, MD study director
Triphase Research and Development I Corp
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NPI-0052 in people with Cancer and Lymphomas, run by Celgene at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: Continuous). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2017.