NCT00920257

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
77

participants targeted

Target at P75+ for phase_1 cancer

Timeline
Completed

Started Jun 2009

Typical duration for phase_1 cancer

Geographic Reach
2 countries

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 12, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 15, 2009

Completed
1 day until next milestone

Study Start

First participant enrolled

June 16, 2009

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 17, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 17, 2013

Completed
Last Updated

November 13, 2017

Status Verified

November 1, 2017

Enrollment Period

3.8 years

First QC Date

June 12, 2009

Last Update Submit

November 8, 2017

Conditions

Cancer

Keywords

oncologybreast cancerAKT inhibitorfirst time in humanlymphomaendometrial cancerGSK2141795solid tumors

Outcome Measures

Primary Outcomes (1)

  • 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

    Continune until disease progression or consent withdrawn

Secondary Outcomes (2)

  • • To explore the clinical efficacy of GSK2141795 in subjects with solid tumor malignancies or lymphomas

    Continune until disease progression or consent withdrawn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

    Continune until disease progression or consent withdrawn

Study Arms (1)

GSK2141795

EXPERIMENTAL

Oral GSK214179 given daily to patients with cancer. Groups of approximately three patients will receive GSK2141795 at increasing doses until a maximum tolerated dose is identified.

Drug: GSK2141795

Interventions

GSK2141795DRUG

GSK2141795 is an oral AKT inhibitor.

GSK2141795

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

GSK Investigational Site

Baltimore, Maryland, 21231-2410, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02115, United States

Location

GSK Investigational Site

New York, New York, 10021, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73104, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

  • Aghajanian C, Bell-McGuinn KM, Burris HA 3rd, Siu LL, Stayner LA, Wheler JJ, Hong DS, Kurkjian C, Pant S, Santiago-Walker A, Gauvin JL, Antal JM, Opalinska JB, Morris SR, Infante JR. A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors. Invest New Drugs. 2018 Dec;36(6):1016-1025. doi: 10.1007/s10637-018-0591-z. Epub 2018 Apr 3.

    PMID: 29611022DERIVED

Related Links

MeSH Terms

Conditions

NeoplasmsBreast NeoplasmsLymphomaEndometrial Neoplasms

Interventions

GSK2141795

Condition Hierarchy (Ancestors)

Neoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesUterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Diseases

Study Officials

  • GSK Clinical Trials

    GlaxoSmithKline

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 12, 2009

First Posted

June 15, 2009

Study Start

June 16, 2009

Primary Completion

April 17, 2013

Study Completion

April 17, 2013

Last Updated

November 13, 2017

Record last verified: 2017-11

Locations

US(6)CA(1)