NPI-0052 and Vorinostat in Patients With Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma

Celgene

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma; Melanoma; Lymphoma; Pancreatic Cancer; Non-Small Cell Lung Cancer

Treatments: Drug: NPI-0052 (marizomib) + vorinostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT00667082

NPI-0052-103

Details and patient eligibility

About

This is a clinical trial examining the safety, pharmacokinetics, pharmacodynamics and efficacy of IV NPI-0052 (a proteasome inhibitor) in combination with oral vorinostat (Zolinza; a HDAC inhibitor) in patients with non-small cell lung cancer, pancreatic cancer, melanoma or lymphoma. Proteasome inhibitors block the breakdown of proteins by cells and HDAC inhibitors block modification of proteins regulating gene expression in cells. Both of these actions preferentially affect cancer cells, and the combination of the two has been seen to have a greater effect in laboratory studies.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Karnofsky Performance Status (KPS) at 70% or more.
2. Non-small cell lung cancer, pancreatic adenocarcinoma, melanoma or lymphoma for which a standard, approved therapy is not available. Patients must have lesions that are evaluable by RECIST criteria.
3. All Adverse Events of any prior chemotherapy, surgery, or radiotherapy, must have resolved to CTCAE (v. 3.0) Grade 1 or less(except for hemoglobin).
4. Adequate bone marrow, renal, liver function.
5. Signed informed consent.

Exclusion criteria

1. Recent administration of chemotherapy, biological, immunotherapy or investigational agent, major surgery, or radiotherapy.
2. Intrathecal therapy.
3. Known brain metastases.
4. Significant cardiac disease.
5. Prior treatment with vorinostat or NPI-0052, or other HDACi (including valproic acid) or proteasome inhibitors.
6. Known allergy to any component of vorinostat. Prior hypersensitivity reaction of CTCAE Grade > 3 to therapy containing propylene glycol or ethanol.
7. Pregnant or breast-feeding women.
8. Concurrent, active secondary malignancy for which the patient is receiving therapy.
9. Significant active infection.

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

NPI-0052 + Vorinostat Dose-Escalation

Experimental group

Description:

4 dose-escalation cohorts

Treatment:

Drug: NPI-0052 (marizomib) + vorinostat