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

November 20, 2017 updated by: Celgene

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Mater Adult Hospital
    • South Australia
      • Woodville South, South Australia, Australia, 5001
        • The Queen Elizabeth Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3002
        • Peter MacCallum Cancen Center
      • Melbourne, Victoria, Australia, 3168
        • The Alfred Hospital
      • Wodonga, Victoria, Australia, 3690
        • Border Medical Oncology
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital and University of Western Australia
      • Perth, Western Australia, Australia, 6001
        • Royal Perth Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • proteasome inhibitor
  • marizomib
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:
  • proteasome inhibitor
  • marizomib
Drug: Dexamethasone
20 mg oral or IV day before and day after NPI-0052 dosing.
Other Names:
  • Decadron

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1
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]
Treatment period through 28-days after the last dose of study drug
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Investigators

  • Study Director: Steven D Reich, MD, Triphase Research and Development I Corp

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

February 26, 2008

First Submitted That Met QC Criteria

March 5, 2008

First Posted (Estimate)

March 6, 2008

Study Record Updates

Last Update Posted (Actual)

November 22, 2017

Last Update Submitted That Met QC Criteria

November 20, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NPI-0052-102

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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