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

Condition(s) targeted: Non-Small Cell Lung Cancer; Pancreatic Cancer; Melanoma; Lymphoma

Intervention: NPI-0052 + vorinostat (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Nereus Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Matthew A Spear, MD, Study Director, Affiliation: Nereus Pharmaceuticals, Chief Medical Officer

Overall contact:
Angie M Longenecker, RN, Phone: +1 858 200 8354, Email: alongenecker@nereuspharm.com

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.

Official title: NPI-0052 and Vorinostat in Patients With Non-Small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma

Study design: Other, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

To determine the Maximum tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of the combination NPI-0052 and Vorinostat

To evaluate the pharmacokinetics and pharmacodynamics of NPI-0052 and vorinostat

Secondary outcome:

To evaluate the safety and toxicity profile of the combination of NPI-0052 and vorinostat

To evaluate the anti-tumor activity of NPI-0052 and vorinostat

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Angie M Longenecker, RN, Phone: +1 858 200 8354, Email: alongenecker@nereuspharm.com

The Queen Elizabeth Hospital, Woodville South, South Australia 5011, Australia; Recruiting
Louise Pirc, Phone: + 61 8 8222 6410, Email: louise.pirc@nwahs.sa.gov.au
Sue Yeend, Phone: + 61 8 8222 6410, Email: sue.yeend@nwahs.sa.gov.au
Timothy Price, MD/MBBS, Principal Investigator

Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia; Recruiting
Nancy Olszewski, Phone: + 61 8 8222 4765, Email: Nancy.olszewski@health.sa.gov.au
Christopher Sweeney, MD, Principal Investigator

Sir Charles Gairdner Hospital and University of Western Australia, Nedlands, Western Australia 6009, Australia; Recruiting
Sharon Lobb, RN, Phone: + 61 8 9346 1717, Email: Sharon.Lobb@health.wa.gov.au
Judy Innes-Rowe, RN, Phone: +61 8 9346 4520, Email: Judy.Innes-Rowe@health.wa.gov.au
Michael Millward, MD, Principal Investigator

Starting date: March 2008
Ending date: September 2009
Last updated: October 27, 2008