Solid Tumors MedDRA version: 12.1 Level: LLT Classification code 10059515 Term: Non-small cell lung cancer metastatic
Conditions
Interventions
Product Name: GSK1120212
Product Code: GSK1120212
Pharmaceutical Form: Film-coated tablet
CAS Number: 1187431-43-1
Current Sponsor code: GSK1120212
Concentration unit: mg milligram(s)
Concentration ty
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 2. Age 18 years old or older and able to swallow oral medication. 3. Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology (ECOG) scale for Phase IB/Dose Escalation Cohort. Subjects with ECOG PS of 2 can be enrolled for Phase IB/Expansion Cohort and Phase II. 4. Tumor Type criteria: • Phase IB/Dose Escalation Cohort o Histologically or cytologically confirmed diagnosis of solid tumor malignancy: That is relapsed/refractory OR is potentially responsive to everolimus OR for which there is no standard or curative therapy OR for subjects who refuse standard therapy • Phase IB/Expansion Cohort o Pancreatic cancer: Histologically or cytologically confirmed diagnosis of metastatic pancreatic cancer. Subjects with locally advanced surgically unresectable disease are also eligible. o Measurable disease by RECIST 1.1. • Phase II o KRAS- mutant NSCLC: Histologically or cytologically confirmed diagnosis of metastatic NSCLC o Measurable disease by RECIST 1.1 [Eisenhauer, 2009]. 5. Fasting glucose 40 MlU/mL and estradiol =65 years) yes F.1.3.1 Number of subjects for this age
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Malignancies related to HIV or solid organ transplant. 2. Primary malignant brain tumors. 3. Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of GSK1120212. Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity are permitted with approval of a GSK Medical Monitor if dosing of that agent is terminated at least 14 days prior to the first dose of GSK1120212. 4. Use of an investigational anti-cancer drug within 28 days or 5 half-lives, whichever is shorter preceding the first dose of GSK1120212 – as long as a minimum of 14 days has passed between the last dose of the prior investigational anti-cancer drug and the first dose of GSK1120212. 5. Previous treatment with an mTOR inhibitor unless approved by GSK Medical Monitor. 6. Previous treatment with GSK1120212. 7. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. 8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, DMSO, or excipients (see GSK1120212 Investigator Brochure [GlaxoSmithKline Document Number RM2007/00107/00]. (To date there are no known FDA approved drugs chemically related to GSK1120212). 9. Use of a prohibited medication (as defined in Section 8.2). 10. Current use of anticoagulants (e.g. warfarin, heparin) at therapeutic levels within seven days prior to the first dose of GSK1120212. Low dose (prophylactic) low molecular weight heparin (LMWH) is permitted provided that subject’s PT and PTT meet entry criteria. Subjects required therapeutic levels of LMWH must receive approval from GSK Medical Monitor and monitored appropriately as clinically indicated. 11. Gastrointestinal disease predicted to interfere with absorption of an oral drug, systemic disease, major surgery, or social/psychological issues that in the opinion of investigators would jeopardize compliance with protocol. 12. History of retinal vein occlusion (RVO) or central serous retinopathy (CSR). 13. Predisposing factors to RVO including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy. 14. Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for RVO or CSR. 15. Intraocular pressure > 21mm Hg as measured by tonography. 16. Glaucoma diagnosed within 1 month prior to study Day 1. 17. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Subjects previously treated for these conditions that are asymptomatic and off corticosteroids for at least two weeks are permitted. Subjects are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs). 18. Unresolved toxicity greater than common terminology criteria for adverse events (CTCAE) grade 1 from previous anti-cancer therapy except alopecia (if applicable) unless agreed to by a GSK Medical Monitor and the Investigator. 19. History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks. 20. QTc interval = 480 msecs. 21. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1B component: To determine the safety, tolerability and recommended Phase II dose and regimen of GSK1120212 and everolimus dosed orally in combination. Phase II component: To determine clinical activity of GSK1120212 and everolimus in subjects with KRAS-mutant NSCLC.;Secondary Objective: Phase 1B component: 1) To characterize the steady-state PK of GSK1120212 and everolimus 2) To evaluate the clinical activity of GSK1120212 and everolimus in subjects with solid tumors and pancreatic cancer. 3) To determine if changes in CA 19-9 levels correlate with radiographic response in subjects with pancreatic cancer Phase II component: 1) To characterize the population pharmacokinetics (PK) parameters of GSK1120212 and everolimus when administered daily in subjects with KRASmutant NSCLC. 2) To characterize the durability of response in subjects achieving clinical benefit.;Primary end point(s): Phase 1B: AEs and changes in laboratory values and vital signs. Phase II: Response rate (CR + PR) of GSK1120212 and everolimus in KRAS-mutant NSCLC. | — |
Countries
Germany, Spain
Outcome results
None listed