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A Phase I, Open-Label, Two-Stage Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Oral AKT Inhibitor GSK2141795 in Subjects With Solid Tumors or Lymphomas


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Cancer

Thank you

Trial Information

A Phase I, Open-Label, Two-Stage Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Oral AKT Inhibitor GSK2141795 in Subjects With Solid Tumors or Lymphomas


Inclusion Criteria:



- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- Male or female, 18 years or older.

- Histologically or cytologically confirmed diagnosis of solid tumor malignancy or
lymphoma that is not responsive to standard therapies or for which there is no
approved or curative therapy. Subjects with malignancies related to human
immunodeficiency virus (HIV) or solid organ transplant are excluded.

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

- Able to swallow and retain oral medication.

- Fasting serum glucose <126 mg/dL.

- 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
GSK2141795 until three months after the last dose of GSK2141795.

- A female subject is eligible to participate if she is of non-child bearing potential,
or of child-bearing potential and willing to use adequate birth control

- Adequate organ function

- (Part 2 only - endometrial) Histologically or cytologically confirmed diagnosis of
relapsed or metastatic endometrial cancer.

- (Part 2 only - endometrial) No more than two prior cytotoxic chemotherapy regimens in
the relapsed or metastatic setting. Targeted agents like bevacizumab are not
considered cytotoxic chemotherapy for the purposes of this study

- (Part 2 only, breast) Histologically or cytologically confirmed diagnosis of locally
advanced or metastatic breast cancer.

- (Part 2 only, breast) No more than three prior cytotoxic chemotherapy regimens in the
metastatic setting. Targeted agents like lapatinib, bevacizumab, and trastuzumab are
not considered cytotoxic chemotherapy for the purposes of this study

Exclusion Criteria:

- Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior
nitrosoureas or mitomycin C) prior to the first dose of GSK2141795. Chemotherapy
regimens given continuously or on a weekly basis with limited potential for delayed
toxicity are permitted with approval of a GSK Medical Monitor if dosing of that
chemotherapy is terminated at least 14 days prior to the first dose of GSK2141795.

- Use of an investigational anti-cancer drug within 28 days or five half-lives,
whichever is longer, preceding the first dose of GSK2141795.

- Current use of a prohibited medication or requires any of these medications during
treatment with GSK2141795.

- Current use of anticoagulants at therapeutic levels within seven days prior to the
first dose of GSK2141795, including warfarin, low molecular weight heparin and direct
thrombin inhibitors. Low dose (prophylactic) anticoagulants such as warfarin, low
molecular weight heparin, selective Factor Xa inhibitors or direct thrombin
inhibitors are permitted provided that subject's PT and PTT meet entry criteria.

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

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

- Any major surgery within the last four weeks of screening.

- Unresolved toxicity (except alopecia) greater than or equal to Grade 2 from previous
anti-cancer therapy unless agreed to by a GSK Medical Monitor and the investigator,
and where a GSK Medical Monitor and the investigator consider that the ongoing
toxicity will not introduce additional risk factors and will not interfere with the
study procedures.

- Previously diagnosed diabetes mellitus (type 1 or 2).

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

- History of an allogeneic stem cell transplant. Subjects with a history of an
autologous stem cell transplant are NOT excluded.

- 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.

- Symptomatic or untreated CNS metastases or leptomeningeal involvement. Subjects who
were previously treated for these conditions, and are asymptomatic without
anti-epileptic medications or steroids for at least 2 months are eligible. Subjects
with primary brain tumor are excluded.

- Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
respiratory, hepatic, renal, or cardiac disease).

- QTc interval greater than or equal to 470 msecs.

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

- History of myocardial infarction, acute coronary syndromes (including unstable
angina), coronary angioplasty, or stenting or bypass grafting within the past 6
months.

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

- Pregnant or Lactating females.

- History of HIV infection; history of hepatitis B or C (subject with evidence of
cleared hepatitis B are eligible)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the recommended Phase II dose and schedule of GSK214179 using the following information: safety and tolerability, pharmacokinetic (single and repeat dose administration) and pharmacodynamic data

Outcome Time Frame:

Continune until disease progression or consent withdrawn

Safety Issue:

Yes

Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:

GlaxoSmithKline

Authority:

Canada: Health Canada

Study ID:

112689

NCT ID:

NCT00920257

Start Date:

June 2009

Completion Date:

July 2013

Related Keywords:

  • Cancer
  • oncology
  • breast cancer
  • AKT inhibitor
  • first time in human
  • lymphoma
  • endometrial cancer
  • GSK2141795
  • solid tumors

Name

Location

GSK Investigational SiteSpringfield, Massachusetts  01107
GSK Investigational SiteFort Worth, Texas  76104
GSK Investigational SiteBaltimore, Maryland  21201
GSK Investigational SiteOklahoma City, Oklahoma  73112
GSK Investigational SiteGermantown, Tennessee  38138
GSK Investigational SiteNew York, New York  10021