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Solid TumoursPhase 1NCT01324258

Trial of GSK1120212 and GSK1120212 in Combination With GEM in Japanese Subjects With Solid Tumors

A Phase 1 study testing GSK1120212 and Gemcitabine in people with Solid Tumours, run by GlaxoSmithKline at 2 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Solid Tumours
What is being tested?
GSK1120212 and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
2 sitesJapan
Study dates
24 Jan 2011to 8 Jul 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

Japan2 sites

  • GSK Investigational Site

    Osaka, 589-8511

  • GSK Investigational Site

    Tokyo, 181-8611

Other trials in Japan

About this study

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

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.

Read the detailed description

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.

Conditions
Solid Tumours
Being tested
GSK1120212, Gemcitabine
Keywords
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)
Medical subject headings
Pancreatic Neoplasms, Carcinoma, Non-Small-Cell Lung, Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01324258
Study groupRoleWhat they receive
GSK1120212ExperimentalPart 1-Dose escalation will be conducted to assess PK after single dosing and safety, tolerability, PK and efficacy of GSK1120212 in Japanese subjects with solid tumors using a continuous daily dosing schedule.
Receives: Drug: GSK1120212; Drug: Gemcitabine
GSK1120212+GemcitabineExperimentalPart 2-Further evaluate the safety, tolerability, PK, and efficacy of GSK1120212 in combination with gemcitabine in subjects with non-small cell lung cancer, pancreatic cancer, biliary cancer, urothelial cancer or other tumor types for which 4-week schedule of gemcitabine has been approved using the recommended dose from Part 1 (single agent).
Receives: Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

Secondary outcomes (6)

  1. To assess pharmacokinetics (PK) parameter (AUC, Cmax, tmax etc.) values for GSK1120212

    Individual subject parameter values as well as a descriptive summary (mean, standard deviation, median, minimum, maximum, geometric mean, and the standard deviation, CV% and 95% confidence interval of log-transformed parameters) by dose cohort will be reported.

    Measured: Cycle0, Cycle1 Day1,8,15,22, Cycle2 Day1 in Part 1

  2. To assess pharmacokinetics (PK) parameter (AUC, Cmax, tmax, etc.) values for GSK1120212 and Gemcitabine

    Individual subject parameter values as well as a descriptive summary (mean, standard deviation, median, minimum, maximum, geometric mean, and the standard deviation, CV% and 95% confidence interval of log-transformed parameters) by dose cohort will be reported.

    Measured: Cycle1 Day15 in Part2

  3. Number of participants with the indicated tumor response defined by RECIST v1.1

    Measured: Every eight weeks during the study

  4. Serum level of cyctokines

    Measured: Cycle1 Day15 in Part1 and Part2

  5. Tissue level of expression of the indicated protein including pERK and Ki67 if possible

    Measured: Cycle1 Day15 in Part1 and Part2

  6. Tissue level of gene mutation including BRAF and KRAS if possible

    Measured: Cycle1 Day15 in Part1 and Part2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2011 (estimated)
  2. Study start24 Jan 2011
  3. Primary completion8 Jul 2013
  4. Study completion8 Jul 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01324258
Sponsor's protocol ID
114784
Status last verified
Nov 2017
First submitted
22 Jan 2011
Last updated
13 Nov 2017
Results posted
No
Data monitoring committee
No

Publications

  • Kasuga A, Nakagawa K, Nagashima F, Shimizu T, Naruge D, Nishina S, Kitamura H, Kurata T, Takasu A, Fujisaka Y, Okamoto W, Nishimura Y, Mukaiyama A, Matsushita H, Furuse J. A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors. Invest New Drugs. 2015 Oct;33(5):1058-67. doi: 10.1007/s10637-015-0270-2. Epub 2015 Aug 12.

    PubMed 26259955

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1120212 and Gemcitabine in people with Solid Tumours, run by GlaxoSmithKline at 2 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with adverse events as a measure of safety and tolerability (time frame: Until a subject has a Dose Limiting Toxicity, withdraws from the study or dies). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01324258, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.

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