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

This study has been terminated.
(This study was terminated prematurely due to lack of sufficient exposure following single- and repeat-dosing.)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00695448
First received: June 9, 2008
Last updated: March 15, 2012
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Solid Tumours
Metastatic Breast Cancer
Solid Tumor Cancer
Lymphoma
Endometrial Cancer
Drug: GSK1059615
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Open-Label, Dose-Escalation Study of the Phosphoinositide 3-Kinase Inhibitor GSK1059615 in Patients With Solid Tumors or Lymphoma

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Adverse events (AEs) and changes in laboratory values and vital signs as per protocol. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • time to maximum observed plasma drug concentration, and half-life of GSK1059615. [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Metabolic profiling in plasma and urine, and amount excreted in urine (subset of patients). [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Tumor response as defined by RECIST in the protocol. [ Time Frame: 56 days ] [ Designated as safety issue: No ]
  • Change from baseline in protein markers in tumor and/or blood. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Blood glucose and insulin levels. [ Time Frame: Daily for 28 days ] [ Designated as safety issue: Yes ]

Enrollment: 11
Study Start Date: June 2008
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00695448

Locations
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00695448     History of Changes
Other Study ID Numbers: PIK111051
Study First Received: June 9, 2008
Last Updated: March 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Phosphoinositide 3-kinase inhibitor
solid tumors

Additional relevant MeSH terms:
Breast Neoplasms
Endometrial Neoplasms
Lymphoma
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Diseases
Genital Diseases, Female
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on April 16, 2014