Lymphoma, Melanoma, Multiple Myeloma, Non-Small Cell Lung Cancer, Pancreatic Cancer
Conditions
Keywords
Non small Cell Lung Cancer, Pancreatic Cancer, Melanoma, Lymphoma, Multiple Myeloma
Brief summary
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.
Interventions
DRUGNPI-0052 (marizomib) + vorinostat
NPI-0052 IV injection over 1 to 10 minutes at doses ranging from 0.15 to 0.7 mg/m2 on Days 1, 8, and 15 of each 28-day Cycle Oral vorinostat 300 mg was administered with food on Days 1 to 16 of each 28-day Cycle
Sponsors
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the Maximum tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of the combination NPI-0052 and Vorinostat | continuously |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the pharmacokinetics and pharmacodynamics of NPI-0052 and vorinostat | continuous |
| To evaluate the safety and toxicity profile of the combination of NPI-0052 and vorinostat | continuous |
| To evaluate the anti-tumor activity of NPI-0052 and vorinostat | continuous |
Countries
Australia
Outcome results
None listed