phase i open-label, dose-escalation study of gsk1059615 in patients with solid tumors or lymphoma

Conditions: Solid Tumours

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.


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). * 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.

Keywords: phosphoinositide 3-kinase inhibitor solid tumors