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

Advanced Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00629473
• Other study ID #: NPI-0052-102
• Status: Completed
• Phase: Phase 1
• First received: February 26, 2008
• Last updated: November 20, 2017
• Start date: July 2007
• Est. completion date: April 2013

Study information

• Verified date: November 2017
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancen Center	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital and University of Western Australia	Nedlands	Western Australia
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Mater Adult Hospital	South Brisbane	Queensland
Australia	Border Medical Oncology	Wodonga	Victoria
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052	Assess dose-limiting toxicities during Cycle 1 for each treatment arm	Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)
Secondary	To evaluate the pharmacokinetics activity of NPI-0052	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
Secondary	To evaluate the safety and tolerability of NPI-0052	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Treatment period through 28-days after the last dose of study drug
Secondary	To evaluate the pharmacodynamics of NPI-0052	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