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A Phase I Trial of GSK1120212 and GSK1120212 in Combination With Gemcitabine in Japanese Subjects With Solid Tumors


Phase 1
20 Years
N/A
Open (Enrolling)
Both
Solid Tumours

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Trial Information

A Phase I Trial of GSK1120212 and GSK1120212 in Combination With Gemcitabine in Japanese Subjects With Solid Tumors


GSK1120212 has demonstrated anti-proliferative activity against a broad range of tumors cell
lines and xenograft models. To date, MEK inhibitors have demonstrated evidence of both
pharmacodynamic and clinical activity in early trials.

This is the first clinical experience in Japan with GSK1120212, a novel MEK inhibitor. This
study is designed to identify recommended doses and regimens in Japanese subjects for the
future development of GSK1120212.

This study will be conducted in subject with solid tumors, and GSK1120212 single agent
treatment to assess safety, tolerability, PK and efficacy (Part 1) and combination treatment
with gemcitabine in subjects with non-small cell lung cancer, pancreatic cancer, biliary
cancer, urothelial cancer or other tumor types for which gemcitabine has been approved in
4-week schedule to assess safety, tolerability, PK and efficacy(Part 2) will be conducted in
the same protocol.


Inclusion Criteria:



Correspond Part 1 (Single agent) and Part 2 (Combination)

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form

- Age 20 years old or older at consent given

- Able to swallow and retain orally administered medication and does not have any
clinically significant gastrointestinal abnormalities that may alter absorption such
as malabsorption syndrome or major resection of the stomach or bowels

- Negative for hepatitis B surface (HBs) antigen, hepatitis virus Bc (HBc) antibody,
and HBs antibody. HBs antigen-negative subjects who test positive for both HBc
antibody and HBs antibody or either of them may be eligible when their HBV DNA
quantification result is negative

- Negative HCV antibody test

- Men with a female partner of childbearing potential must have either had a prior
vasectomy or agree to use effective contraception from the time of the first dose of
GSK1120212 until 16 weeks after the last dose of GSK1120212

- A female subject is eligible to participate if she is of;Non-childbearing potential
females or female subjects with child-bearing potential must agree to use
contraception until four weeks after the last dose of GSK1120212 to sufficiently
minimize the risk of pregnancy at that point

Part 1 -Dose escalation single agent part

- Histologically or cytologically confirmed diagnosis of solid tumor malignancy that is
not responsive to standard therapies or for which there is no approved or curative
therapy. Subjects with primary brain tumor are excluded

- Adequate organ system functions as defined below; Absolute neutrophil count≥1,200/uL
Hemoglobin≥9g/dL Platelets≥75,000/uL PT/INR and APTT≤1.3xULN Albumin≥2.5g/dL Total
bilirubin≤1.5xULN AST and ALT≤2.5xULN Creatinine≤ULN OR Calculated creatinine
clearance≥50mL/min OR 24-hour urine creatinine clearance≥50mL/min Left ventricular
Ejection fraction≥LLN by ECHO or MUGA

Part 2 -Combination part

- Tumor type criteria;Histologically or cytologically confirmed diagnosis of solid
tumor malignancy. Eligible are the cancers for which gemcitabine has been approved in
4-week schedule;1,000mg/m2 weekly for 3weeks followed by 1 week rest at the 4th week,
including non-small cell lung cancer, pancreatic cancer, biliary cancer, and
urothelial cancer, to which gemcitabine monotherapy is considered to be appropriate

- Adequate organ system functions as defined below; Absolute neutrophil count≥1,500/uL
Hemoglobin≥9g/dL Platelets≥100,000/uL PT/INR and APTT1≤1.3xULN Albumin≥2.5g/dL Total
bilirubin≤1.5xULN AST and ALT≤2.5xULN Creatinine≤ULN OR Calculated creatinine
clearance≥50mL/min OR 24-hour urine creatinine clearance≥50mL/min Left ventricular
Ejection fraction≥LLN by ECHO or MUGA

Exclusion Criteria:

Correspond Part 1 (Single agent) and Part 2 (Combination)

- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
conditions that could interfere with subject's safety, obtaining informed consent or
compliance to the study procedures

- Use of an investigational anti-cancer drug within 28 days or five half-lives,
whichever is shorter preceding the first dose of GSK1120212. Or use of an other
investigational drug within 28 days or five half-lives, whichever is longer preceding
the first dose of GSK1120212

- Previous treatment with a MEK inhibitor

- 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
subinvestigator, contraindicates their participation

- History of interstitial lung disease or pneumonitis

- Current use of a prohibited medication

- Any major surgery, radiotherapy, or immunotherapy within 21 days before initiation of
GSK1120212. Or chemotherapy regimens with delayed toxicity within 21 days before
initiation of GSK1120212. Or chemotherapy regimens given continuously or on a weekly
basis with limited potential for delayed toxicity within the two weeks before
initiation of GSK1120212

- History or current evidence/risk of retinal vein occlusion (RVO) or central serous
retinopathy (CSR)

- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression

- QTc B≥480 msecs

- History of acute coronary syndromes (including unstable angina), coronary
angioplasty, or stenting within the past 24 weeks

- History or evidence of current≥Class II congestive heart failure as defined by New
York Heart Association

- History or evidence of current clinically significant uncontrolled arrhythmias

- History of HIV infection

- Evidence of severe or uncontrolled systemic diseases

- Unresolved toxicity greater than CTCAE (Version 3.0) Grade 1 from previous
anti-cancer therapy except alopecia

- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to
dimethyl sulfoxide (DMSO)

- Pregnant or lactating female

- 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

- Unwillingness or inability to follow the procedures outlined in the protocol

Part 1 -Dose escalation single agent part

- History of another malignancy

- Presence of active gastrointestinal disease or other condition that will interfere
significantly with the absorption, distribution, metabolism, or excretion of drugs

Part 2 -Combination part

- History of another malignancy

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of participants with adverse events as a measure of safety and tolerability

Outcome Time Frame:

Until a subject has a Dose Limiting Toxicity, withdraws from the study or dies

Safety Issue:

Yes

Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:

GlaxoSmithKline

Authority:

Japan: Ministry of Health, Labor and Welfare

Study ID:

114784

NCT ID:

NCT01324258

Start Date:

January 2011

Completion Date:

September 2013

Related Keywords:

  • Solid Tumours
  • pancreatic cancer (combination with gemcitabine)
  • Non-small cell lung cancer (combination with gemcitabine)
  • solid tumors (single agent)
  • MEK inhibitor
  • GSK1120212
  • biliary cancer (combination with gemcitabine)
  • urothelial cancer (combination with gemcitabine)
  • Neoplasms

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