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Report for Clinical Trial NCT02447939

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I Study to Evaluate the Pharmacokinetics and Safety of Repeat Oral Doses of Dabrafenib and the Combination of Dabrafenib With Trametinib in Chinese Subjects With Melanoma

Present clinical study will be conducted in China to evaluate the pharmacokinetics (PK) of single and repeat oral doses of dabrafenib alone and dabrafenib and trametinib in combination, the safety profile and the clinical activity of dabrafenib in combination with trametinib in Chinese melanoma subjects with BRAF V600E/K mutation. Approximately 20 evaluable subjects will be enrolled in the study, out of which, the first 10 subjects will be enrolled into cohort A (Part I and II) and remaining 10 subjects will be enrolled in cohort B. Subjects in cohort A (Part I) will receive dabrafenib 150 mg twice daily (BID) and subjects in cohort A (Part II) and Cohort B will receive combination of dabrafenib 150 mg BID and trametinib 2 mg once daily (QD). Study treatment will continue until disease progression, death or unacceptable toxicity. After disease progression, all enrolled subjects will be followed up for overall survival. The study will be completed after all subjects have died or surviving subjects have had at least 5 years of follow-up, whichever occurs first.

NCT02447939 Melanoma
MeSH:Melanoma
HPO:Cutaneous melanoma Melanoma

2 Interventions

Name: Dabrafenib

Description: Dabrafenib will be provided as 50 mg and 75 mg capsules. Each capsule will contain 50 mg or 75 mg of free base (present as the mesylate salt).
Type: Drug
Group Labels: 1

Dabrafenib and Trametinib

Name: Trametinib

Description: 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)
Type: Drug
Group Labels: 1

Dabrafenib and Trametinib


Primary Outcomes

Description: Maximum observed plasma concentration (Cmax), time to Cmax (Tmax) and area under the concentration-time curve over the dosing interval [AUC(0-tau)] will be calculated for dabrafenib and its metabolites.

Measure: Composite of PK parameters of dabrafenib and its metabolites following single and repeat dabrafenib (150 mg BID) dose: Cmax,Tmax and AUC(0-tau)

Time: At Day 1: Pre dose, 1,2, 3, 4, 6, 8, 12 and 24 h post dose.

Description: Tmax, minimum concentration at steady state (Css_min), maximum concentration at steady state (Css_max), average concentration at steady state (Css_av), AUC(0-tau) will be calculated for dabrafenib and its metabolites.

Measure: A Composite of PK parameters of dabrafenib and its metabolites following single and repeat dabrafenib (150 mg BID) dose : Tmax, Css_min, Css_max, Css_av and AUC(0-tau)

Time: At Day 21: Pre dose, 1,2, 3, 4, 6, 8, 12 and 24 h post dose.

Measure: Accumulation ratio of dabrafenib and its metabolites following single and repeat dabrafenib (150 mg BID) dose

Time: At Day 21.

Measure: Composite of PK parameters of dabrafenib and its metabolites following single and repeat dabrafenib (150 mg BID) and trametinib (2 mg QD) dose: Cmax, Tmax, AUC(0-tau)

Time: At Day 1: Pre dose, 1,2, 3, 4, 6, 8, 12 and 24 h post dose.

Measure: Composite of PK parameters of dabrafenib and its metabolites following single and repeat dabrafenib (150 mg BID) and trametinib (2 mg QD) dose : Tmax, Css_min, Css_max, Css_av, AUC(0-tau)

Time: At Day 21: Pre dose, 1,2, 3, 4, 6, 8, 12 and 24 h post dose.

Measure: Accumulation ratio of dabrafenib and its metabolites following single and repeat dabrafenib (150 mg BID) and trametinib (2 mg QD) dose

Time: At Day 21.

Measure: Composite of PK parameters of trametinib following single and repeat dabrafenib (150 mg BID) and trametinib (2 mg QD) dose: Cmax, Tmax, AUC(0-tau)

Time: At Day 1: Pre dose, 1,2, 3, 4, 6, 8, 12 and 24 h post dose.

Measure: Composite of PK parameters of trametinib following single and repeat dabrafenib (150 mg BID) and trametinib (2 mg QD) dose : Tmax, Css_min, Css_max, Css_av, AUC(0-tau)

Time: At Day 21: Pre dose, 1,2, 3, 4, 6, 8, 12 and 24 h post dose.

Measure: Accumulation ratio of trametinib following single and repeat dabrafenib (150 mg BID) and trametinib (2 mg QD) dose

Time: At Day 21.

Measure: Effective half-life of trametinib following single and repeat dabrafenib (150 mg BID) and trametinib (2 mg QD) dose

Time: At Day 21.

Secondary Outcomes

Description: 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.

Measure: Composite of Physical examination assessment

Time: Up to 30 days of the subject's last dose (assessed up to 5 years).

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

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

Time: Up to 30 days of the subject's last dose (assessed up to 5 years).

Description: 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).

Measure: Electrocardiogram (ECG) assessment

Time: Up to 30 days of the subject's last dose (assessed up to 5 years).

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

Measure: Echocardiogram (ECHO) assessment

Time: At week 4, week 8, and then every 8 weeks until treatment discontinuation.

Description: Eye exam will include indirect fundoscopic examination,visual acuity, visual field examination, and tonometry, with special attention to retinal abnormalities.

Measure: Eye exams assessment

Time: At screening, and when clinical indicated until treatment discontinuation.

Measure: Chemistry laboratory values assessment

Time: Up to 30 days of the subject's last dose (assessed up to 5 years).

Measure: Number of subjects with Adverse events (AEs)

Time: Up to 5 years.

Measure: Number of subjects with Serious Adverse events (SAEs)

Time: Up to 5 years.

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

Measure: Objective response rate (ORR)

Time: Up to 5 years.

Description: 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.

Measure: Progression free survival(PFS)

Time: Up to 5 years.

Description: OS defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact.

Measure: Overall survival(OS)

Time: Up to 5 years.

Measure: Hematology laboratory values assessment

Time: Up to 30 days of the subject's last dose (assessed up to 5 years).

Measure: Urinalysis laboratory values assessment

Time: Up to 30 days of the subject's last dose (assessed up to 5 years).

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 V600E

Pharmacokinetics of Repeat Oral Doses of Dabrafenib and the Combination of Dabrafenib and Trametinib in Chinese Subjects With Melanoma Present clinical study will be conducted in China to evaluate the pharmacokinetics (PK) of single and repeat oral doses of dabrafenib alone and dabrafenib and trametinib in combination, the safety profile and the clinical activity of dabrafenib in combination with trametinib in Chinese melanoma subjects with BRAF V600E/K mutation. --- V600E ---

- Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and BRAF V600E/K mutation-positive from the designated qualified laboratory for this study. --- V600E ---



HPO Nodes


HPO: