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

NCT ID: NCT00629473

Last Updated: 2017-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-07-31

Study Completion Date

2013-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Advanced Cancer

Keywords

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multiple myeloma leukemias (inc. CLL) lymphomas cutaneous lymphoma marginal zone lymphoma advanced malignancies without standard treatment options

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

NPI-0052 on Days 1, 8, 15 every 28 days

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

NPI-0052 on Days 1, 4, 8, 11 every 21 days

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

20 mg oral or IV day before and day after NPI-0052 dosing.

Interventions

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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

Intervention Type 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

Intervention Type DRUG

Dexamethasone

20 mg oral or IV day before and day after NPI-0052 dosing.

Intervention Type DRUG

Other Intervention Names

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marizomib proteasome inhibitor marizomib proteasome inhibitor Decadron

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Steven D Reich, MD

Role: STUDY_DIRECTOR

Triphase Research and Development I Corp

Locations

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Mater Adult Hospital

South Brisbane, Queensland, Australia

Site Status

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Site Status

Peter MacCallum Cancen Center

Melbourne, Victoria, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Border Medical Oncology

Wodonga, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital and University of Western Australia

Nedlands, Western Australia, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

Countries

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Estonia Australia

Other Identifiers

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NPI-0052-102

Identifier Type: -

Identifier Source: org_study_id