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Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma

Primary Purpose

Cancer, Lymphomas

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

NPI-0052

About this trial

This is an interventional treatment trial for Cancer focused on measuring cutaneous lymphoma, marginal zone lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
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.

Sites / Locations

Premiere Oncology of America
Memorial Sloan-Kettering Cancer Center
Univ. of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NPI-0052

Arm Description

Advanced Solid Tumor Malignancies and Refractory Lymphoma

Outcomes

Primary Outcome Measures

Safety

Maximum Tolerated Dose (MTD)

Pharmacokinetics

Secondary Outcome Measures

Pharmacodynamics

Response

Full Information

NCT ID

NCT00396864

First Posted

November 6, 2006

Last Updated

November 20, 2017

Sponsor

Celgene

1. Study Identification

Unique Protocol Identification Number

NCT00396864

Brief Title

Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma

Official Title

Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Completed

Study Start Date

May 2006 (undefined)

Primary Completion Date

March 2010 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celgene

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cancer, Lymphomas

Keywords

cutaneous lymphoma, marginal zone lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

51 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NPI-0052

Arm Type

Experimental

Arm Description

Advanced Solid Tumor Malignancies and Refractory Lymphoma

Intervention Type

Drug

Intervention Name(s)

NPI-0052

Other Intervention Name(s)

Marizomib, MRZ

Intervention Description

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

Primary Outcome Measure Information:

Title

Safety

Time Frame

Continuous

Title

Maximum Tolerated Dose (MTD)

Time Frame

Continuous

Title

Pharmacokinetics

Time Frame

Continuous

Secondary Outcome Measure Information:

Title

Pharmacodynamics

Time Frame

Continuous

Title

Response

Time Frame

Continous

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven D Reich, MD

Organizational Affiliation

Triphase Research and Development I Corp

Official's Role

Study Director

Facility Information:

Facility Name

Premiere Oncology of America

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85260

Country

United States

Facility Name

Memorial Sloan-Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

Univ. of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Solid Tumor Malignancies or Refractory Lymphoma

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