Last updated: 11/03/2018 13:26:42
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
A Phase I, Open-Label, First-Time-In-Human Study of the Oral AKT Inhibitor GSK2141795
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: 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
Trial description: This study is a first time in human, Phase I, open-label, dose-escalation study of the oral AKT inhibitor GSK2141795 in subjects with solid tumors or lymphomas.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
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
Timeframe: Continune until disease progression or consent withdrawn
Secondary outcomes:
• To explore the clinical efficacy of GSK2141795 in subjects with solid tumor malignancies or lymphomas
Timeframe: Continune until disease progression or consent withdrawn
To characterize the metabolite profile of oral GSK2141795 after repeat dose administration in subjects with solid tumor malignancies or lymphoma
Timeframe: Continune until disease progression or consent withdrawn
Interventions:
Drug: GSK2141795
Enrollment:
77
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Cancer
Product
uprosertib
Collaborators
Not applicable
Study date(s)
June 2009 to April 2013
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion criteria
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)
Trial location(s)
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21231-2410
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73104
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02115
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10021
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
No longer a GSK study
Actual primary completion date
Not applicable
Actual study completion date
2013-17-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Results for study 112689 can be found on the GSK Clinical Study Register.
Click hereAccess to clinical trial data by researchers
Visit website