Repeat Dose Safety Study for Compound to Treat Hematologic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Accenture
ClinicalTrials.gov Identifier:
NCT00881946
First received: March 20, 2009
Last updated: April 3, 2012
Last verified: April 2012
  Purpose

The purpose of this study is to characterize the safety and tolerability of repeat doses of compound GSK2110183 in subjects with hematologic cancer.


Condition Intervention Phase
Hematologic Malignancies
Drug: GSK21110183
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official 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

Resource links provided by NLM:


Further study details as provided by Accenture:

Primary Outcome Measures:
  • Physical exam [ Time Frame: Screening, Days -3, 8, At the start of each additional Cycle ] [ Designated as safety issue: Yes ]
  • Electrocardiogram (ECG) [ Time Frame: Days -3, -2, -1, 8, 15, At the start of each additional Cycle ] [ Designated as safety issue: Yes ]
  • Vital signs [ Time Frame: Screening, Days -3, -2, -1, 8, 15, At the start of each additional Cycle ] [ Designated as safety issue: Yes ]
  • Transthoracic Echocardiogram (TTE)/Multiple Gated Acquisition (MUGA) Scans [ Time Frame: Screening, Additionally as needed ] [ Designated as safety issue: Yes ]
  • Clinical Laboratory assessments [ Time Frame: Screening, Days -3, 1, 8, 15, At the start of each additional Cycle ] [ Designated as safety issue: Yes ]
  • ECOG Peformance Status [ Time Frame: Screening, Days -3, 8, At the start of each additional Cycle ] [ Designated as safety issue: Yes ]
  • PK - Maximum observed plasma concentraion (Cmax) [ Time Frame: Days -3, -2, -1, 8, 15 ] [ Designated as safety issue: No ]
  • PK - time to Cmax [tmax] (Maximum observed plasma concentration) [ Time Frame: Days -3, -2, -1, 8, 15 ] [ Designated as safety issue: No ]
  • PK - Area under the plasma concentration-time curve (AUC(0-t)) [ Time Frame: Days -3, -2, -1, 8, 15 ] [ Designated as safety issue: No ]
  • PK - Apparent terminal phase elimination rate constant [ Time Frame: Days -3, -2, -1, 8, 15 ] [ Designated as safety issue: No ]
  • PK - Apparent terminal phase half-life (t1/2) [ Time Frame: Days -3, -2, -1, 8, 15 ] [ Designated as safety issue: No ]
  • PK - oral clearance (CL/F) [ Time Frame: Days -3, -2, -1, 8, 15 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Metabolite Profiling [ Time Frame: Days -3, 8 ] [ Designated as safety issue: No ]

Enrollment: 73
Study Start Date: July 2009
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2119183 Drug: GSK21110183
Starting Dose = 25mg once daily with dose escalation until unacceptable toxicity develops

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00881946

Locations
Australia, New South Wales
Prince of Wales Hospital
Sydney, New South Wales, Australia, 2031
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia, 3004
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
Accenture
Investigators
Study Director: S. Jamie Freedman, MD, PhD
  More Information

No publications provided

Responsible Party: Accenture
ClinicalTrials.gov Identifier: NCT00881946     History of Changes
Other Study ID Numbers: PKB112835
Study First Received: March 20, 2009
Last Updated: April 3, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Accenture:
chronic lymphocytic leukemia
aggressive lymphoma
non-Hodgkin's lymphoma
Hodgkin's lymphoma
chronic myelogenous leukemia
multiple myeloma
acute lymphoblastic leukemia
acute myeloid leukemia

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on July 24, 2014