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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00667082




Registration number
NCT00667082
Ethics application status
Date submitted
22/04/2008
Date registered
25/04/2008
Date last updated
22/11/2017

Titles & IDs
Public title
NPI-0052 and Vorinostat in Patients With Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma
Scientific title
NPI-0052 and Vorinostat in Patients With Non-small Cell Lung Cancer, Pancreatic Cancer, Melanoma or Lymphoma
Secondary ID [1] 0 0
NPI-0052-103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Pancreatic Cancer 0 0
Melanoma 0 0
Lymphoma 0 0
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NPI-0052 (marizomib) + vorinostat

Experimental: NPI-0052 + Vorinostat Dose-Escalation - 4 dose-escalation cohorts


Treatment: Drugs: NPI-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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To determine the Maximum tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of the combination NPI-0052 and Vorinostat
Timepoint [1] 0 0
continuously
Secondary outcome [1] 0 0
To evaluate the pharmacokinetics and pharmacodynamics of NPI-0052 and vorinostat
Timepoint [1] 0 0
continuous
Secondary outcome [2] 0 0
To evaluate the safety and toxicity profile of the combination of NPI-0052 and vorinostat
Timepoint [2] 0 0
continuous
Secondary outcome [3] 0 0
To evaluate the anti-tumor activity of NPI-0052 and vorinostat
Timepoint [3] 0 0
continuous

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Other
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [3] 0 0
Sir Charles Gairdner Hospital and University of Western Australia - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment postcode(s) [3] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00667082
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Steven D Reich, MD
Address 0 0
Triphase Research and Development I Corp
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications