Last updated: 11/07/2018 04:24:54
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
A study of the GSK MEK inhibitor GSK1120212 and everolimus in cancer subjectsCancer
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: An Open-Label, Dose-Escalation, Phase IB II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor GSK1120212 in Combination with Oral Everolimus in Subjects with Solid Tumors
Trial description: The purpose of this study is to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with everolimus in subjects with solid tumors. The escalation part of the study will determine the MTD. The combination will be further explored in the expansion part in subjects with metastatic pancreatic cancer. In addition, subjects with KRAS mutant non-small cell lung cancer will be enrolled.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
AEs and changes in laboratory values and vital signs
Timeframe: 6 months
Response rate, CR + PR of GSK1120212 and everolimus in KRAS-mutant NSCLC.
Timeframe: 6 months
Secondary outcomes:
GSK1120212 and everolimus PK parameters following repeat-dose (Day 15) administration of GSK1120212 and everolimus, including AUC(0-tau), Ct, Cmax, tmax, and t1/2, data permitting
Timeframe: 6 months
Tumor response as defined by RECIST 1.1.
Timeframe: 6 months
CA 19-9 levels compared to radiological response, per RECIST 1.1, over time for each pancreatic cancer subject
Timeframe: 6 months
Population PK parameters, oral clearance and oral volume of distribution of GSK1120212 and everolimus will be determined. Dependant upon the final compartmental model describing GSK1120212 + everolimus, add. PK may also be estimated.
Timeframe: 6 months
Clinical benefit response rate CR+PR+SD greater than 4mos
Timeframe: 6 months
Duration of response
Timeframe: 6 months
Interventions:
Drug: GSK1120212 plus everolimus
Enrollment:
64
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Tolcher A, Bendell JC, Papadopoulos KP, Burris HA, Patnaik A, Jones SF, Rasco D, Cox DS, Durante M, Bellew KM, Park JJ, Le NT, Infante JR.A Phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors.Ann Oncol.2014;26(1):58-64
Tolcher A, Bendell JC, Papadopoulos KP, Burris HA, Patnaik A, Jones SF, Rasco D, Cox DS, Durante M, Bellew KM, Park JJ, Le NT, Infante JR.A Phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors.Ann Oncol.2015;26(1):58-64
Medical condition
Cancer
Product
trametinib
Collaborators
Not applicable
Study date(s)
August 2009 to November 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Age 18 years old or older and able to swallow oral medication.
- Malignancies related to HIV or solid organ transplant.
- Primary malignant brain tumors.
Inclusion and exclusion criteria
Inclusion criteria:
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Age 18 years old or older and able to swallow oral medication.
- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology (ECOG) scale for Dose Escalation Cohort. Subjects with ECOG of 2 can be enrolled for expansion cohort.
- Tumor Type criteria as listed in the protocol
- Fasting glucose < 126mg/dL
- Male subjects must agree to use one of the contraception methods listed in the protocol.
- A female subject is eligible to participate if she is of non-childbearing potential, and if she is of childbearing potential she must use protocol defined contraception methods.
- Calcium phosphate product less than or equal to 4.0 mmol2/L2 (50 mg2/dL2)
- Adequate organ system function as defined below in the protocol.
Exclusion criteria:
- Malignancies related to HIV or solid organ transplant.
- Primary malignant brain tumors.
- 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.
- 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.
- Previous treatment with an mTOR inhibitor unless approved by GSK Medical Monitor.
- Previous treatment with GSK1120212.
- 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.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, DMSO, or excipients. (To date there are no known FDA approved drugs chemically related to GSK1120212).
- Use of a prohibited medication (as defined in the protocol).
- 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.
- 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.
- History of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
- Predisposing factors to RVO including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy.
- Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for RVO or CSR.
- Intraocular pressure > 21mm Hg as measured by tonography.
- Glaucoma diagnosed within 1 month prior to study Day 1.
- 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).
- 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.
- History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks.
- QTc interval ≥ 480 msecs.
- Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Pregnant or lactating female.
- History or active hepatitis B or C.
- History of HIV infection.
- Subjects on chronic antifungal therapy.
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial location(s)
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Terminated/Withdrawn
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
No longer a GSK study
Actual primary completion date
Not applicable
Actual study completion date
2011-08-11
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
Participate in clinical trial
Additional information
Results for study 112110 can be found on the GSK Clinical Study Register.
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