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Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00629473
Recruitment Status : Completed
First Posted : March 6, 2008
Last Update Posted : November 22, 2017
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:
This is a Phase 1 clinical trial examining the safety, pharmacokinetics and pharmacodynamics of escalating doses of the proteasome inhibitor NPI-0052 in patients with advanced malignancies including solid tumors, lymphomas, leukemias and multiple myeloma. By inhibiting proteasomes NPI-0052 prevents the breakdown of proteins involved in signal transduction, which blocks growth and survival in cancer cells.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: NPI-0052 on Days 1, 8, 15 every 28 days Drug: NPI-0052 on Days 1, 4, 8, 11 every 21 days Drug: Dexamethasone Phase 1

Detailed Description:

Patients were enrolled in 1 of 2 study arms. Arm AM (weekly doses of NPI-0052) consisted of patients with solid and hematological malignancies excluding multiple myeloma (MM), and these patients received NPI-0051 once weekly for 3 weeks of every 4 weeks. Arm MM (twice-weekly doses of NPI-0052) consisted of patients with MM and other hematological malignancies, and these patients received NPI-0052 twice weekly for 2 weeks of every 3 weeks. All patients received NPI-0052 administered IV over approximately 1 to 120 minutes. Patients with MM (Arm MM) also received 20 mg dexamethasone per orally or IV on the day before and the day of NPI-0052 dosing.

Patients were initially enrolled in dose-escalating cohorts to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of NPI-0052. Once the RP2D was determined for each arm of the study, the RP2D was evaluated in the dose-expansion stage of the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
Study Start Date : July 2007
Actual Primary Completion Date : April 2013
Actual Study Completion Date : April 2013


Arm Intervention/treatment
Experimental: Arm AM: advanced malignancies
Dose Escalation - 9 dose cohorts NPI-0052 on Days 1, 8, 15 every 28 days NPI-0052 doses ranging from 0.1 to 0.9 mg/m2
Drug: NPI-0052 on Days 1, 8, 15 every 28 days
NPI-0052 dose ranging from 0.1 to 0.9 mg/m2 NPI-0052 IV injection over 1 to 120 minutes on Days 1, 8, and 15 of 4-week cycles
Other Names:
  • marizomib
  • proteasome inhibitor

Experimental: Arm MM: multiple myeloma
Dose Escalation - 8 dose cohorts NPI-0052 on Days 1, 4, 8, 11 every 21 days NPI-0052 doses ranging from 0.075 to 0.6 mg/m2 Dexamethasone 20 mg oral or IV day before and day after NPI-0052 dosing.
Drug: NPI-0052 on Days 1, 4, 8, 11 every 21 days
NPI-0052 dose ranging from 0.075 to 0.6 mg/m2 NPI-0052 IV injection over 1 to 120 minutes on Days 1, 4, 8, and 11 of 3-week cycles
Other Names:
  • marizomib
  • proteasome inhibitor

Drug: Dexamethasone
20 mg oral or IV day before and day after NPI-0052 dosing.
Other Name: Decadron




Primary Outcome Measures :
  1. Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052 [ Time Frame: Cycle 1 (Arm AM: 28-days, Arm MM: 21-days) ]
    Assess dose-limiting toxicities during Cycle 1 for each treatment arm


Secondary Outcome Measures :
  1. To evaluate the pharmacokinetics activity of NPI-0052 [ Time Frame: Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1 ]
    the assess the time course of NPI-0052 in the body

  2. To evaluate the safety and tolerability of NPI-0052 [ Time Frame: Treatment period through 28-days after the last dose of study drug ]
    Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  3. To evaluate the pharmacodynamics of NPI-0052 [ Time Frame: Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycles 1 and 2 and of every other cycle thereafter through study completion ]
    proteasome inhibition in blood samples



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Karnofsky Performance Status (KPS) > 70%.
  • Histologically-confirmed advanced malignancy for which a standard, approved therapy is not available.
  • Adequate renal, liver, pancreatic and hematologic function
  • Signed informed consent (sample IC form is provided in Appendix A).

Exclusion Criteria

  • Administration of chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 28 days
  • Patients that require G-CSF and/or platelet support during screening and are likely to require G-CSF and/or platelet support for the duration of the clinical trial.
  • Patients with ongoing coagulopathies and/or taking anticoagulants
  • Patients receiving intrathecal therapy.
  • Known brain metastases.
  • Pre-existing adrenal insufficiency; concomitant therapy with replacement corticosteroids. Pre-existing acute or chronic pancreatitis.
  • Significant cardiac disease.
  • Pregnant or breast-feeding women.
  • Concurrent, active secondary malignancy for which the patient is receiving therapy. (Lymphoma patients with a diagnosis of a potentially hormone-sensitive tumor who are without evidence of disease for this second malignancy may continue to receive hormonal therapy).
  • Patients with proteinuria Grade 2 or greater
  • Active uncontrolled bacterial or fungal infection requiring systemic therapy; infection requiring parenteral antibiotics.
  • Patients who are known to be HIV positive or have active Hepatitis A, B, or C infection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00629473


Locations
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Australia, Queensland
Mater Adult Hospital
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia, 5001
Australia, Victoria
Peter MacCallum Cancen Center
Melbourne, Victoria, Australia, 3002
The Alfred Hospital
Melbourne, Victoria, Australia, 3168
Border Medical Oncology
Wodonga, Victoria, Australia, 3690
Australia, Western Australia
Sir Charles Gairdner Hospital and University of Western Australia
Nedlands, Western Australia, Australia, 6009
Royal Perth Hospital
Perth, Western Australia, Australia, 6001
Sponsors and Collaborators
Celgene
Investigators
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Study Director: Steven D Reich, MD Triphase Research and Development I Corp
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT00629473    
Other Study ID Numbers: NPI-0052-102
First Posted: March 6, 2008    Key Record Dates
Last Update Posted: November 22, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Celgene:
multiple myeloma
leukemias (inc. CLL)
lymphomas
cutaneous lymphoma
marginal zone lymphoma
advanced malignancies without standard treatment options
Additional relevant MeSH terms:
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Neoplasms
Dexamethasone
Proteasome Inhibitors
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action