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CancerPhase 1NCT02939846

Pharmacokinetics of Single and Repeat Oral Doses of Trametinib in Chinese Subjects With Solid Tumours

A Phase 1 study testing Trametinib in people with Cancer, run by GlaxoSmithKline.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Present clinical study will be conducted in China to evaluate the pharmacokinetics of single and repeat oral doses of trametinib, the safety profile and the clinical activity in Chinese subjects with solid tumor. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer
What is being tested?
Trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
May 2017to Dec 2018
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provided signed written informed consent
  • Males and females ≥18 years of age (at the time consent is obtained).
  • Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumours, melanoma subjects will be eligible if BRAF V600 mutation was confirmed in the tumour tissue by qualified clinical laboratories. The disease is not responsive to standard therapies, or for which there is no approved or curative therapy.
  • Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
  • Adequate baseline organ function defined by: Absolute neutrophil count (ANC): >=1,200 /microliter (uL); Hemoglobin: >=9 grams (g)/deciliter (dL); Platelets: >=75,000 /uL; Prothrombin time/ International normalization ratio and activated partial thromboplastin time: <=1.5 x Upper Limit of Normal (ULN); Total bilirubin: <=1.5 x ULN; Aspartate aminotransferase and Alanine aminotransferase: <=2.5 x ULN; Calculated creatinine clearance (Calculate creatinine clearance using standard Cockcroft-Gault formula): >=50 milliliter (mL)/ minute (min) or 24-hour urine creatinine clearance>=50 mL/min; Left ventricular Ejection fraction (LVEF): >/= 50% LVEF in case there is no established Lower limit of normal (LLN) for a given institution.
  • 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. Subjects with prior Whipple procedure (pancreaticoduodenectomy) are eligible (if meeting above criteria).
  • 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 trametinib until 16 weeks after the last dose of trametinib.
  • Women of child-bearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception from 14 days prior to enrolment, throughout the treatment period and for 4 months after the last dose of study treatment.

Who cannot join

  • Pregnant or Lactating female.
  • History of another malignancy. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  • Use of an investigational drug within 28 days or five half-lives, whichever is longer preceding the first dose of trametinib.
  • 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 sub-investigator, contraindicates their participation.
  • History of interstitial lung disease or pneumonitis.
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  • Current use of a prohibited medication as described in Section 10.2.
  • •Colony-stimulating factors like filgrastim are prohibited during treatment as a prophylactic management.
  • Any major surgery, radiotherapy, or immunotherapy within 21 days before initiation of trametinib. Chemotherapy regimens with delayed toxicity within 21 days before initiation of trametinib (42 days for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the two weeks before initiation of trametinib.
  • Note: Use of bisphosphonates is considered supportive care and their use is permitted.
  • History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):
  • Uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).
  • Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:
  • Evidence of new optic disc cupping
  • Evidence of new visual field defects on automated perimetry
  • Intraocular pressure > 21mm Hg as measured by tonography
  • Symptomatic or uncontrolled leptomeningeal or brain metastases or spinal cord compression.
  • Subjects previously treated for these conditions that have had stable central nervous system (CNS) disease are asymptomatic and off corticosteroids, or are on stable dose of corticosteroids for at least 1 month prior to study Day 1 are eligible.
  • Subjects are not eligible to receive enzyme inducing anti-epileptic drugs (EIAEDs).
  • 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.
  • Subjects with controlled atrial fibrillation for >1 month prior to study Day 1 are eligible.
  • History of Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
  • Subjects with laboratory evidence of cleared HBV and/or HCV will be permitted, which defined as HBs antigen negative and HBV DNA negative(HBV DNA result is mandatory if both or either HBc and HBs antibody is positive); and HCV antibody is negative.
  • History of HIV infection.
  • Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease).
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to dimethyl sulfoxide (DMSO).
  • Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures.

About this study

Official title: A Phase I Study to Evaluate the Pharmacokinetics and Safety of Single and Repeat Oral Doses of Trametinib in Chinese Subjects With Solid Tumours

Present clinical study will be conducted in China to evaluate the pharmacokinetics of single and repeat oral doses of trametinib, the safety profile and the clinical activity in Chinese subjects with solid tumor. Approximately 10 evaluable subjects will be enrolled in the study, Subjects will receive trametinib 2 mg once daily (QD). Study treatment will continue until disease progression, death or unacceptable toxicity. The study will be completed after all subjects have discontinued from study treatment or last enrolled subject has had at least 16 weeks of follow-up, whichever occurs first.

Conditions
Cancer
Being tested
Trametinib
Keywords
Safety, Solid tumor, Trametinib, Pharmacokinetics
Medical subject headings
Neoplasms

What participants receive

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

  • TrametinibDrug

    Trametinib study will be provided as 0.5 mg and 2.0 mg tablets. Each tablet will contain 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)

Study groups in NCT02939846
Study groupRoleWhat they receive
TrametinibExperimentalSubjects will be administrated with trametinib 2 mg once daily until disease progression.
Receives: Drug: Trametinib

What is being measured

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

  1. PK parameters of trametinib following single and repeat dose(2mg QD): Cmax

    Measured: At Day 1:Pre-dose, 0.5hr,1hr, 2hr,3hr,4hr, 6hr,10hr,24hr

  2. PK parameters of trametinib following single and repeat dose(2mg QD): Tmax

    Measured: At Day 1:Pre-dose, 0.5hr,1hr, 2hr,3hr,4hr, 6hr,10hr,24hr

  3. PK parameters of trametinib following single and repeat dose(2mg QD): AUC (0-24h)

    Measured: At Day 1:Pre-dose, 0.5hr,1hr, 2hr,3hr,4hr, 6hr,10hr,24hr

  4. PK parameters of trametinib following single and repeat dose(2mg QD): Cmin.ss

    Measured: At Day 22:Pre-dose, 0.5hr,1hr, 2hr,3hr,4hr, 6hr,10hr,24hr

  5. PK parameters of trametinib following single and repeat dose(2mg QD): Cmax.ss

    Measured: At Day 22:Pre-dose, 0.5hr,1hr, 2hr,3hr,4hr, 6hr,10hr,24hr

  6. PK parameters of trametinib following single and repeat dose(2mg QD): Cavg.ss

    Measured: At Day 22:Pre-dose, 0.5hr,1hr, 2hr,3hr,4hr, 6hr,10hr,24hr

  7. PK parameters of trametinib following single and repeat dose(2mg QD): AUC(0-24h)

    Measured: At Day 22:Pre-dose, 0.5hr,1hr, 2hr,3hr,4hr, 6hr,10hr,24hr

  8. Accumulation ratio of trametinib following single and repeat dose(2mg QD)

    Measured: At Day 22

  9. Effective half-life of trametinib following single and repeat dose(2mg QD)

    Measured: At Day 22

Secondary outcomes (12)

  1. Composite of Physical examination assessment

    Physical examination will include assessments of eyes, neurological and cardiovascular systems, lungs, abdomen, head, neck, ears, nose, mouth, throat, thyroid, lymph nodes, extremities, and skin, genitourinary (pelvic) and rectal exams.

    Measured: Up to 30 days of the subject's last dose

  2. Composite of Safety and tolerability as assessed by vital signs assessment: blood pressure, temperature and pulse rate

    Vital sign measurements will include systolic and diastolic blood pressure, body temperature and pulse rate.

    Measured: Up to 30 days of the subject's last dose.

  3. Electrocardiogram (ECG) assessment

    12-lead ECGs will be obtained at each time point using an ECG machine that automatically to calculate the heart rate and measures PR, QRS, QT and corrected QT interval duration (QTc intervals).

    Measured: Every week in the 1st month, week 8, and then every 8 weeks until treatment discontinuation up to 30 days of the subject's last dose (assessed up to 5 years)

  4. Echocardiogram (ECHO) assessment

    ECHO assessment will include an evaluation for left ventricular ejection fraction.

    Measured: At week 4, week 8, and then every 8 weeks until treatment discontinuation up to 5 years

  5. Eye exams assessment

    Measured: At screening, and when clinical indicated until treatment discontinuation up to 5 years

  6. Chemistry laboratory values assessment

    Measured: Up to 30 days of the subject's last dose.

  7. Number of subjects with Adverse events (AEs)

    Measured: Up to 30 days of the subject's last dose.

  8. Number of subjects with Serious Adverse events (SAEs)

    Measured: Up to 30 days of the subject's last dose.

  9. Objective response rate (ORR)

    ORR defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation

    Measured: Every 2 months until disease progression up to 5 years

  10. Progression free survival(PFS)

    PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause

    Measured: Every 2 months until disease progression up to 5 years

  11. Hematology laboratory values assessment

    Measured: Up to 30 days of the subject's last dose

  12. Urinalysis laboratory values assessment

    Measured: Up to 30 days of the subject's last dose

Timeline

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

  1. First posted20 Oct 2016 (estimated)
  2. Study startMay 2017 (estimated)
  3. Primary completionAug 2018 (estimated)
  4. Study completionDec 2018 (estimated)

Why it stopped: Change in strategy

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02939846
Sponsor's protocol ID
201021
Status last verified
Jan 2017
First submitted
7 May 2015
Last updated
14 Sep 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Trametinib in people with Cancer, run by GlaxoSmithKline.

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 8 inclusion and 30 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: withdrawn, as of the sponsor's last update on 14 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

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 was withdrawn before enrolling participants, so there are no results.

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?

PK parameters of trametinib following single and repeat dose(2mg QD): Cmax (time frame: At Day 1:Pre-dose, 0.5hr,1hr, 2hr,3hr,4hr, 6hr,10hr,24hr). The study lists 9 primary outcomes in all. 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 NCT02939846.

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 14 Sep 2018.

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