Last updated: 11/04/2018 10:14:53
Phase I Open-Label, Dose-Escalation Study of GSK1059615 in Patients with Solid Tumors or Lymphoma
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official title: A Phase I Open-Label, Dose-Escalation Study of the Phosphoinositide 3-Kinase Inhibitor GSK1059615 in Patients with Solid Tumors or Lymphoma
Trial description: This is an open-label, multi-center Phase I study conducted to define the recommendedPhase 2 dose, toxicity profile, pharmacokinetics and biologically active dose range of GSK1059615.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Adverse events (AEs) and changes in laboratory values and vital signs as per protocol.
Timeframe: 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)
Timeframe: 21 days
time to maximum observed plasma drug concentration, and half-life of GSK1059615.
Timeframe: 21 days
Metabolic profiling in plasma and urine, and amount excreted in urine (subset of patients).
Timeframe: 21 days
Tumor response as defined by RECIST in the protocol.
Timeframe: 56 days
Change from baseline in protein markers in tumor and/or blood.
Timeframe: 28 days
Blood glucose and insulin levels.
Timeframe: Daily for 28 days
Interventions:
Enrollment:
11
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Solid Tumours
Product
GSK1059615
Collaborators
Not applicable
Study date(s)
June 2008 to March 2009
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Written informed consent provided.
- 18 years old or older.
- Use of an investigational anti-cancer drug within 28 days or 5 half-lives preceding
- the first dose of GSK1059615.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Houston, Texas, United States, 77030-4009
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Other
Actual primary completion date
Not applicable
Actual study completion date
2009-31-03
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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