A Study of the GSK MEK Inhibitor GSK1120212 and Everolimus in Cancer Subjects

NCT00955773 | Completed Phase 1

• 1 other identifier: 112110
• Study Type: interventional
• Target: 64
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Cancer

Keywords

GSK1120212, everolimus, solid tumors, pancreatic cancer, non-small lung cancer, KRAS-mutant; cancer

Outcome Measures

Primary Outcomes (2)

• AEs and changes in laboratory values and vital signs

  6 months

• Response rate, CR + PR of GSK1120212 and everolimus in KRAS-mutant NSCLC.

  6 months

Secondary Outcomes (6)

• 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

  6 months

• Tumor response as defined by RECIST 1.1.

  6 months

• CA 19-9 levels compared to radiological response, per RECIST 1.1, over time for each pancreatic cancer subject

  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.

  6 months

• Clinical benefit response rate CR+PR+SD greater than 4mos

  6 months

Study Arms (3)

Group I

EXPERIMENTAL

20 to 30 solid tumor subjects will be dosed with GSK1120212 in combination with everolimus to identify Maximum Tolerated Dose. Subjects will continue on study drug until disease progression or withdraw consent.

Drug: GSK1120212 plus everolimus

Group II

EXPERIMENTAL

20 subjects with pancreatic cancer will receive the recommended dose identified in group I. Subjects will remain on study drug until disease progression or withdrawal from consent.

Drug: GSK1120212 plus everolimus

Group III

EXPERIMENTAL

Approximately 40 lung cancer subjects will receive the recommended dose identified in group I. Subjects will remain on study until disease progression or withdrawal of consent.

Drug: GSK1120212 plus everolimus

Interventions

GSK1120212 plus everolimus DRUG

Dose escalation will begin at low doses of GSK1120212 and everolimus, then gradually increase in future cohorts. Dose escalation will continue until a recommended combination dose is identified. The recommended combination dose will be used to treat pancreatic and lung cancer patients in later groups in this study.

Group I; Group II; Group III

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Paris, 75970, France

Location

Related Publications (1)

• Tolcher AW, Bendell JC, Papadopoulos KP, Burris HA 3rd, Patnaik A, Jones SF, Rasco D, Cox DS, Durante M, Bellew KM, Park J, 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 Jan;26(1):58-64. doi: 10.1093/annonc/mdu482. Epub 2014 Oct 24.

  PMID: 25344362 DERIVED

Related Links

• Results for study 112110 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Neoplasms; Pancreatic Neoplasms

Interventions

trametinib; Everolimus

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2009
• First Posted: August 10, 2009
• Study Start: August 17, 2009
• Primary Completion: November 8, 2011
• Study Completion: November 8, 2011
• Last Updated: November 9, 2017

Record last verified: 2017-11

Locations

US (2); FR (1)