Phase I Open-Label, Dose-Escalation Study of GSK1059615 in Patients With Solid Tumors or Lymphoma

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumours
• Intervention / Treatment: Drug: GSK1059615

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77030-4009
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).
• A female is eligible to enroll in the study if she is of:

Non-child bearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who is characterized by at least one of the following:

• Has had a hysterectomy
• Has had a bilateral oophorectomy (ovariectomy)
• Has had a bilateral tubal ligation
• Is post-menopausal (total cessation of menses for ≥ 1 year) Childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following from at least 2 weeks prior to the first dose of study drug and until 21 days after last dose of study medication:
• Use an intrauterine device (IUD) with a documented failure rate of
• less than 1% per year.
• Have intercourse only with a vasectomized partner who is sterile
• and is the sole sexual partner for that woman.
• Complete abstinence from sexual intercourse.
• Use double barrier contraception defined as condom with
• spermicidal jelly, foam, suppository, or film; OR diaphragm with
• spermicide; OR male condom and diaphragm. NOTE: Oral contraceptives are not reliable due to potential for drug-drug interaction.
• Adequate organ system function as defined in the protocol.

Exclusion Criteria:

• Use of an investigational anti-cancer drug within 28 days or 5 half-lives preceding the first dose of GSK1059615.
• 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.
• Unresolved toxicity greater than Grade 1 from previous anti-cancer therapy except alopecia. Patients with stable Grade 2 neuropathy can be enrolled with approval by the GSK Medical Monitor.
• QTc interval ≥ 480 msecs.
• History of acute coronary syndromes (including unstable angina and myocardial infarction), atrial fibrillation, coronary angioplasty, or stenting within the past 24 weeks.
• Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• Symptomatic or untreated leptomeningeal or brain metastases. Patients previously treated for these conditions who are asymptomatic and off of corticosteroid and P450-inducing anti-epileptic medication for at least 2 months are permitted.
• Primary malignancy of the central nervous system.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
• Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol.
• Nursing female.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohorts; The starting dose is 6mg once daily (QD); dose is to be escalated using a standard 3 + 3 dose escalation scheme.	Drug: GSK1059615; GSK1059615 is dosed orally once daily for 21 days of a 28-day cycle. Patients continue treatment for subsequent cycles as long as eligible and receiving benefit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events (AEs) and changes in laboratory values and vital signs as per protocol.	21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2008
• Primary Completion (Actual): March 31, 2009
• Study Completion (Actual): March 31, 2009

Study Registration Dates

• First Submitted: June 9, 2008
• First Submitted That Met QC Criteria: June 9, 2008
• First Posted (Estimate): June 11, 2008

Study Record Updates

• Last Update Posted (Actual): July 25, 2017
• Last Update Submitted That Met QC Criteria: July 23, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: solid tumors; Phosphoinositide 3-kinase inhibitor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: PIK111051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Study Protocol
   Information identifier: PIK111051
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: PIK111051
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: PIK111051
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: PIK111051
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: PIK111051
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: PIK111051
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: PIK111051
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register