Combination Study of GSK1120212 With Gemcitabine in Subjects With Solid Tumors

NCT01428427 | Completed Phase 1

• 1 other identifier: 112111
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

MEK112111 is a dose-escalation, Phase IB, open-label, single-arm, multi-center study. The primary objective of the study is to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with gemcitabine in subjects with solid tumors.

Conditions

Leukaemia, Myelocytic, Acute

Keywords

Gemcitabine; MEK inhibitor; GSK1120212

Outcome Measures

Primary Outcomes (1)

• Adverse events (AEs) and changes in laboratory values and vital signs.

  From date of randomization until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.

Secondary Outcomes (2)

• Tumor response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v 1.1

  At screening and every 8 weeks until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.

• drug levels in blood

  first 15 days on study

Study Arms (1)

Cohort

EXPERIMENTAL

Dose escalation to maximum tolerated dose of GSK1120212 and Gemcitabine.

Drug: GSK1120212; Drug: Gemcitabine

Interventions

GSK1120212 DRUG

Continuous daily oral dosing while on study or disease progression (cycle = 28 days).

Cohort

Gemcitabine DRUG

Dosing once weekly for 3 weeks in a 28 day cycle until disease progression.

Cohort

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.
• Histologically or cytologically confirmed diagnosis of a solid tumor malignancy that is either relapsed or refractory, or potentially responsive to gemcitabine.
• Tumor Type criteria as listed in protocol.
• Male subjects must agree to use one of the contraception methods listed in protocol.
• A female subject is eligible to participate if she is of non-childbearing potential as defined in the protocol or postmenopausal as defined in the protocol. If of child-bearing potential, she agrees to use protocol specified contraceptive methods
• Adequate organ system function as defined below in the protocol.

You may not qualify if:

• Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of GSK1120212.
• Use of an investigational anti-cancer drug within 28 days or five 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.
• 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, dimethy sulfoxide (DMSO), or excipients (See protocol)
• Use of a prohibited medication (as defined in protocol) or current use of anticoagulants (e.g. warfarin, heparin, low molecular weight heparin) at therapeutic levels. Low dose (prophylactic) anticoagulants are permitted provided that subject's prothrombin time (PT) and partial thromboplastin time (PTT) meet entry criteria.
• Gastrointestinal disease predicted to interfere with absorption of an oral drug.
• History of retinal vein occlusion (RVO) or central serous retinopathy.
• Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein thrombosis.
• Glaucoma diagnosed within one month prior to study day 1.
• Intraocular pressure \> 21mm Hg as measured by tonography.
• 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 months 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 v4.0) grade 1 from previous anti-cancer therapy.
• History of acute coronary within the past 24 weeks.
• QTc interval greater than or equal to 480 mili seconds (msecs).
• Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Infante JR, Papadopoulos KP, Bendell JC, Patnaik A, Burris HA 3rd, Rasco D, Jones SF, Smith L, Cox DS, Durante M, Bellew KM, Park JJ, Le NT, Tolcher AW. A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours. Eur J Cancer. 2013 Jun;49(9):2077-85. doi: 10.1016/j.ejca.2013.03.020. Epub 2013 Apr 11.

  PMID: 23583440 BACKGROUND

Related Links

• Results for study 112111 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Leukemia

Interventions

trametinib; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

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: December 10, 2009
• First Posted: September 5, 2011
• Study Start: August 12, 2009
• Primary Completion: July 18, 2011
• Study Completion: July 18, 2011
• Last Updated: November 13, 2017

Record last verified: 2017-11

Locations

US (2)