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

NCT02939846 | Withdrawn Phase 1

• 1 other identifier: 201021
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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

Keywords

Safety; Solid tumor; Trametinib; Pharmacokinetics

Outcome Measures

Primary Outcomes (9)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  At Day 22

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

  At Day 22

Secondary Outcomes (12)

• Composite of Physical examination assessment

  Up to 30 days of the subject's last dose

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

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

• Electrocardiogram (ECG) assessment

  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)

• Echocardiogram (ECHO) assessment

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

• Eye exams assessment

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

Study Arms (1)

Trametinib

EXPERIMENTAL

Subjects will be administrated with trametinib 2 mg once daily until disease progression.

Drug: Trametinib

Interventions

Trametinib DRUG

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)

Trametinib

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Neoplasms

Interventions

trametinib

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: October 20, 2016
• Study Start: May 1, 2017
• Primary Completion: August 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 14, 2018

Record last verified: 2017-01