SCCA Breast Cancer Clinical Trials
|Closed||Advanced Solid Tumor or Lymphoma||Phase I||
This study is a Phase I, first-time-in-human dose escalation study in subjects with refractory solid tumors or lymphoma. The primary objective of this study is to determine the recommended Phase II dose of GSK2126458 based on safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity. Secondary objectives are to characterize the pharmacokinetics of GSK2126458; and to explore relationships between GSK2126458 pharmacokinetics, pharmacodynamics, response prediction biomarkers and clinical endpoints.
Subjects with solid tumors or lymphoma will initially receive oral GSK2126458 daily for 28 consecutive days in each 28 day cycle. Subjects may be dosed once or twice a day or may be dosed on an intermittent schedule depending on the safety, pharmacokinetic and pharmacodynamic results that become available as the study progresses. The starting dose will be 0.1 mg once a day. Expansion of some cohorts will be conducted to test tumor pharmacodynamics, further explore the toxicity profile and to look for preliminary evidence of activity in subjects with tumors with PIK3CA mutations. The recommended Phase II dose will be the lowest dose explored (at or below MTD) that maintains biologic activity with an acceptable tolerability profile.
|Ages Eligible for Study:||18 Years and older|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
- 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. Availability of archived tissue is required for all subjects participating in any of the expanded cohorts.
- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
- 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 medication 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 medication and until 21 days after last dose of study medication, or is surgically sterile and agrees to use a condom or occlusive cap (NOTE: Male subjects must use contraception to prevent pregnancy in a female partner and prevent exposure of any partner to semen by any means).
- 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: Has had a hysterectomy, Has had a bilateral oophorectomy (ovariectomy),Has had a bilateral tubal ligation or ablation. 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 medication 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. Completely abstain 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.
- Adequate organ system function
- Use of an investigational anti-cancer medication within 28 days or 5 half-lives preceding the first dose of GSK2126458.
- 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 medication.
- 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 medication. (To date there are no known FDA approved drugs chemically related to GSK2126458).
- Current use of a prohibited medication or requires any of these medications during treatment with GSK2126458.
- 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. Subjects 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 or subjects receiving clopidogrel bisulfate therapy [Plavix]), 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.
- History of conditions (including past history of stroke or subarachnoid hemorrhage) which could increase the risk of complications from hypertension.
- Systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg. Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure must be re-assessed prior to dosing and the SBP / DBP values from each blood pressure assessment prior to dosing on the day of dosing must be < 140/90mmHg in order for a subject to be eligible for the study.
- Diabetes Mellitus (Type I or II)
- Symptomatic or untreated leptomeningeal or brain metastases.
- 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, unless she agrees to discontinue breastfeeding before receiving the first dose of study medication.
See this trial at ClinicalTrials.gov
Access protocol and consent forms at Fred Hutchinson Cancer Research Center
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