A Phase I Open-Label, Dose-Escalation Study of the Phosphoinositide 3-Kinase Inhibitor GSK1059615 in Patients With Solid Tumors or Lymphoma

GlaxoSmithKline1 site in 1 country11 target enrollmentJune 24, 2008

ConditionsSolid Tumours

InterventionsGSK1059615

DrugsGSK1059615

Overview

Phase: Phase 1
Intervention: GSK1059615
Conditions: Solid Tumours
Sponsor: GlaxoSmithKline
Enrollment: 11
Locations: 1
Primary Endpoint: Adverse events (AEs) and changes in laboratory values and vital signs as per protocol.
Status: Terminated
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, multi-center Phase I study conducted to define the recommended Phase 2 dose, toxicity profile, pharmacokinetics and biologically active dose range of GSK1059615.

Registry

clinicaltrials.gov

Start Date

June 24, 2008

End Date

March 31, 2009

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Written informed consent provided.
•18 years old or older.
•Histologically- or cytologically- confirmed diagnosis of solid tumor malignancy or lymphoma that is not responsive to accepted standard therapies or for which there is no standard or curative therapy.
•Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
•A life expectancy of \> 12 weeks.
•Able to swallow and retain oral medication.
•A male is eligible to enter and participate in the study if he either:
•agrees to abstain from sexual intercourse from the first dose of study drug and until 21 days after last dose of study medication, or
•agrees to use a condom and occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository from the first dose of study drug and until 21 days after last dose of study medication, or
•is surgically sterile. NOTE: Male patients must use contraception to prevent pregnancy in a female partner and prevent exposure of any partner to semen by any means (refer to protocol).

Exclusion Criteria

•Use of an investigational anti-cancer drug within 28 days or 5 half-lives preceding the first dose of GSK
•Chemotherapy within the last 3 weeks (6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity are permitted with approval of the GSK medical monitor if administered at least 2 weeks prior to the first dose of study drug.
•Trastuzumab within the last 4 weeks.
•Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks.
•Prior use of any PI3K inhibitor.
•Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug. (To date there are no known FDA approved drugs chemically related to GSK1059615).
•Current use of a prohibited medication or requires any of these medications during treatment with GSK1059615 as per protocol.
•Current use of warfarin for therapeutic anticoagulation.
•NOTE: Low molecular weight heparin and prophylactic low-dose warfarin are permitted. PT/PTT must meet the inclusion criteria. Patients taking warfarin must have their INR followed closely.
•Presence of an active gastrointestinal disease or other condition known to interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.

Arms & Interventions

Cohorts

The starting dose is 6mg once daily (QD); dose is to be escalated using a standard 3 + 3 dose escalation scheme.

Intervention: GSK1059615

Outcomes

Primary Outcomes

Adverse events (AEs) and changes in laboratory values and vital signs as per protocol.

Time Frame: 21 days

Secondary Outcomes

Pharmacokinetic parameter values for GSK1059615 following single and repeated dosing, including area under the plasma drug concentration curve (AUC), maximum observed plasma drug concentration (Cmax)(21 days)
time to maximum observed plasma drug concentration, and half-life of GSK1059615.(21 days)
Metabolic profiling in plasma and urine, and amount excreted in urine (subset of patients).(21 days)
Tumor response as defined by RECIST in the protocol.(56 days)
Change from baseline in protein markers in tumor and/or blood.(28 days)
Blood glucose and insulin levels.(Daily for 28 days)