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

NCT00695448 | Terminated Phase 1

• 1 other identifier: PIK111051
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

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.

Conditions

Solid Tumours

Keywords

Phosphoinositide 3-kinase inhibitor; solid tumors

Outcome Measures

Primary Outcomes (1)

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

  21 days

Secondary Outcomes (6)

• 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

Study Arms (1)

Cohorts

EXPERIMENTAL

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

Drug: GSK1059615

Interventions

GSK1059615 DRUG

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.

Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent provided.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Houston, Texas, 77030-4009, United States

Location

Related 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 Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 9, 2008
• First Posted: June 11, 2008
• Study Start: June 24, 2008
• Primary Completion: March 31, 2009
• Study Completion: March 31, 2009
• Last Updated: July 25, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

US (2)