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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/NCT00881946




Registration number
NCT00881946
Ethics application status
Date submitted
20/03/2009
Date registered
15/04/2009
Date last updated
4/04/2012

Titles & IDs
Public title
Repeat Dose Safety Study for Compound to Treat Hematologic Cancer
Scientific title
A Phase I, Open-Label, Two-Stage Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Oral AKT Inhibitor GSK2110183 in Subjects With Any Hematologic Malignancy
Secondary ID [1] 0 0
PKB112835
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hematologic Malignancies 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK21110183

Experimental: GSK2119183 -


Treatment: Drugs: GSK21110183
Starting Dose = 25mg once daily with dose escalation until unacceptable toxicity develops
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Physical exam
Timepoint [1] 0 0
Screening, Days -3, 8, At the start of each additional Cycle
Primary outcome [2] 0 0
Electrocardiogram (ECG)
Timepoint [2] 0 0
Days -3, -2, -1, 8, 15, At the start of each additional Cycle
Primary outcome [3] 0 0
Vital signs
Timepoint [3] 0 0
Screening, Days -3, -2, -1, 8, 15, At the start of each additional Cycle
Primary outcome [4] 0 0
Transthoracic Echocardiogram (TTE)/Multiple Gated Acquisition (MUGA) Scans
Timepoint [4] 0 0
Screening, Additionally as needed
Primary outcome [5] 0 0
Clinical Laboratory assessments
Timepoint [5] 0 0
Screening, Days -3, 1, 8, 15, At the start of each additional Cycle
Primary outcome [6] 0 0
ECOG Peformance Status
Timepoint [6] 0 0
Screening, Days -3, 8, At the start of each additional Cycle
Primary outcome [7] 0 0
PK - Maximum observed plasma concentraion (Cmax)
Timepoint [7] 0 0
Days -3, -2, -1, 8, 15
Primary outcome [8] 0 0
PK - time to Cmax [tmax] (Maximum observed plasma concentration)
Timepoint [8] 0 0
Days -3, -2, -1, 8, 15
Primary outcome [9] 0 0
PK - Area under the plasma concentration-time curve (AUC(0-t))
Timepoint [9] 0 0
Days -3, -2, -1, 8, 15
Primary outcome [10] 0 0
PK - Apparent terminal phase elimination rate constant
Timepoint [10] 0 0
Days -3, -2, -1, 8, 15
Primary outcome [11] 0 0
PK - Apparent terminal phase half-life (t1/2)
Timepoint [11] 0 0
Days -3, -2, -1, 8, 15
Primary outcome [12] 0 0
PK - oral clearance (CL/F)
Timepoint [12] 0 0
Days -3, -2, -1, 8, 15
Secondary outcome [1] 0 0
Metabolite Profiling
Timepoint [1] 0 0
Days -3, 8

Eligibility
Key inclusion criteria
1. Written informed consent is provided.

2. Male or female who is at least 18 years of age or older.

3. Histologically- or cytologically-confirmed diagnosis of a hematologic malignancy -
that has relapsed or is refractory after standard therapy, AND that is not associated
with human immunodeficiency virus (HIV) infection or solid organ transplant,
including:

- chronic lymphocytic leukemia (CLL),

- chronic myelogenous leukemia (CML),

- multiple myeloma (MM),

- non-Hodgkin's lymphoma (NHL),

- Hodgkin's lymphoma, or

- Other hematologic malignancy excluding:

- acute leukemia of any type

- CML blast crisis

- myelodysplastic syndrome (MDS)

- myelofibrosis

4. Performance Status score of 0 and 1 according to the Eastern Cooperative Oncology
Group (ECOG) scale

5. Able to swallow and retain oral medication.

6. Fasting serum glucose < 126 mg/dL (<7 mmol/L).

7. Male subjects with a female partner of childbearing potential must have had a prior
vasectomy or agree to use adequate contraception from the time of the first dose of
study drug until three months after the last dose of study drug.

8. A female subject is eligible to participate if she is of:

- Non-childbearing potential

- Child-bearing potential, has a negative serum pregnancy test during the screening
period, and agrees to use adequate contraception from screening until four weeks
after the last dose of study drug.

9. Adequate organ system function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior
nitrosoureas or mitomycin C) prior to the first dose of study drug.

2. Use of an investigational anti-cancer drug within 28 days or five half-lives,
whichever is longer, preceding the first dose of study drug.

3. Current use of a prohibited medication or requires any of these medications during
treatment with study drug.

4. Current use of anticoagulants at therapeutic levels within seven days prior to the
first dose of study drug, including warfarin, low molecular weight heparin and direct
thrombin inhibitors. Low dose (prophylactic) anticoagulants are permitted provided
that subject's PT and PTT meet entry criteria.

5. Current use of any anti-platelet agent (e.g. dipyridamole, clopidogrel) other than
aspirin (81 mg daily).

6. Presence of active gastrointestinal disease or other condition that could affect
gastrointestinal absorption (e.g. malabsorption syndrome) or predispose subject to
gastrointestinal ulceration.

7. Any major surgery within the last four weeks.

8. Unresolved toxicity (except alopecia) Grade 2 from previous anti-cancer therapy unless
agreed to by a Medical Monitor and the Investigator

9. Previously diagnosed diabetes mellitus (Type 1 or 2).

10. Current use of oral corticosteroids, with the exception of inhaled or topical
corticosteroids.

11. Any serious or unstable pre-existing medical, psychiatric, or other condition
(including lab abnormalities) that could interfere with subject safety or with
obtaining informed consent.

12. Symptomatic or untreated central nervous system (CNS) involvement by the hematologic
malignancy (including primary CNS lymphoma).

13. Evidence of severe or uncontrolled systemic diseases

14. Known infection with HIV, HBV or HCV.

15. QTc interval = 470 msecs.

16. Other clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd
degree atrioventricular (AV) block.

17. History of myocardial infarction, acute coronary syndromes (including unstable
angina), coronary angioplasty, or stenting or bypass grafting within the past six
months.

18. Class III or IV heart failure as defined by the New York Heart Association (NYHA)
functional classification system.

19. Pregnant or lactating female.

20. Active drug or alcohol abuse.

21. History of sensitivity to heparin or heparin-induced thrombocytopenia.

Study design
Purpose of the study
Basic Science
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/Phase 2
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
1/07/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2012
Sample size
Target
Accrual to date
Final
73
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Ontario
Country [2] 0 0
Korea, Republic of
State/province [2] 0 0
Seoul

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to characterize the safety and tolerability of repeat doses of
compound GSK2110183 in subjects with hematologic cancer.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00881946
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
S. Jamie Freedman, MD, PhD
Address 0 0
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