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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00629473




Registration number
NCT00629473
Ethics application status
Date submitted
26/02/2008
Date registered
6/03/2008
Date last updated
22/11/2017

Titles & IDs
Public title
Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
Scientific title
A Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
Secondary ID [1] 0 0
NPI-0052-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NPI-0052 on Days 1, 8, 15 every 28 days
Treatment: Drugs - NPI-0052 on Days 1, 4, 8, 11 every 21 days
Treatment: Drugs - Dexamethasone

Experimental: Arm AM: advanced malignancies - Dose Escalation - 9 dose cohorts NPI-0052 on Days 1, 8, 15 every 28 days NPI-0052 doses ranging from 0.1 to 0.9 mg/m2

Experimental: Arm MM: multiple myeloma - Dose Escalation - 8 dose cohorts NPI-0052 on Days 1, 4, 8, 11 every 21 days NPI-0052 doses ranging from 0.075 to 0.6 mg/m2 Dexamethasone 20 mg oral or IV day before and day after NPI-0052 dosing.


Treatment: Drugs: 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

Treatment: Drugs: 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

Treatment: Drugs: Dexamethasone
20 mg oral or IV day before and day after NPI-0052 dosing.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052
Timepoint [1] 0 0
Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)
Secondary outcome [1] 0 0
To evaluate the pharmacokinetics activity of NPI-0052
Timepoint [1] 0 0
Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1
Secondary outcome [2] 0 0
To evaluate the safety and tolerability of NPI-0052
Timepoint [2] 0 0
Treatment period through 28-days after the last dose of study drug
Secondary outcome [3] 0 0
To evaluate the pharmacodynamics of NPI-0052
Timepoint [3] 0 0
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

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
1/07/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2013
Sample size
Target
Accrual to date
Final
86
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [3] 0 0
Peter MacCallum Cancen Center - Melbourne
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [6] 0 0
Sir Charles Gairdner Hospital and University of Western Australia - Nedlands
Recruitment hospital [7] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
5001 - Woodville South
Recruitment postcode(s) [3] 0 0
3002 - Melbourne
Recruitment postcode(s) [4] 0 0
3168 - Melbourne
Recruitment postcode(s) [5] 0 0
3690 - Wodonga
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
6001 - Perth

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

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00629473
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00629473