CompletedPhase 1

Study of Dabrafenib +/- Trametinib in Combination With Ipilimumab for V600E/K Mutation Positive Metastatic or Unresectable Melanoma

United States38 participantsStarted 2013-02-12

Plain-language summary

This is an open-label, multi-center, dose-finding Phase 1 study that will enroll subjects at least 18 years old with unresectable or metastatic melanoma and BRAF V600 mutations. The primary objective of the study is to describe the safety for the doublet therapy (dabrafenib and ipilimumab) and the triplet therapy (dabrafenib/trametinib and ipilimumab). Preliminary efficacy data will also be collected. Subjects will be assigned to receive either the doublet combination (dabrafenib and ipilimumab) or the triplet combination (dabrafenib, trametinib, and ipilimumab). Subjects will be enrolled to dose-finding cohorts in the doublet combination (dabrafenib + ipilimumab) in a sequential 3+3 fashion. Following establishment of a dose for the doublet combination, an expansion cohort will be opened. At the same time, enrollment to dose finding cohorts for the triplet combination (dabrafenib + trametinib + ipilimumab) will begin in a sequential 6+6 fashion. Enrollment into triplet cohorts will take priority when both the doublet expansion arm and the triplet dose-finding arm are open for enrollment at the same time. Approximately 9-24 subjects will be enrolled to the dose finding portion of the study. Approximately 30 subjects will be enrolled to doublet expansion cohort and 30 subjects will be enrolled in the triplet expansion cohort. A two-week run-in period without ipilimumab will be followed by 4 intravenous doses of ipilimumab at the recommended dose and schedule. Oral daily dosing of dabrafenib or dabrafenib + trametinib will continue from the two-week run-in, through combination with ipilimumab, and post-ipilimumab until no longer of clinical benefit, in the opinion of the treating physician, or until unacceptable AE or death

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Exclusion criteria

✕. All known lesions were previously treated with surgery or stereotactic surgery (whole-brain radiation is not allowed unless given after definitive treatment with surgery or stereotactic surgery) AND
✕. Brain lesion(s), if still present, must be confirmed stable (i.e., no increase in lesion size) for \>= 6 weeks prior to randomization (stability must be confirmed with two consecutive magnetic resonance image (MRI) or computed tomography (CT) scans with contrast, AND
✕. Asymptomatic with no corticosteroid requirements for \>= 4 weeks prior to randomization, AND
✕. No enzyme inducing anticonvulsants for \>= 4 weeks prior to randomization
✕. LVEF \< LLN for the institution
✕. A corrected QT interval \>=480 msec (e.g. Bazett's formula \[QTcB\])
✕. A history or evidence of current clinically significant uncontrolled arrhythmias (exception: subjects with controlled atrial fibrillation for \> 30 days prior to randomization are eligible)
✕. A history (within 6 months prior to first dose of study treatment) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty

What they're measuring

Number of subjects with Adverse Events (AEs) to assess the safety of dabrafenib +/- trametinib when administered in combination with ipilimumab

Timeframe: Follow-up up to 6 months after last subject last dose

Changes in laboratory values, vital signs, and physical examinations as a measure of safety of dabrafenib +/- trametinib when administered in combination with ipilimumab

Timeframe: Follow-up up to 6 months after last subject last dose

Trial details

NCT IDNCT01767454

SponsorGlaxoSmithKline

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2015-09-04

View on ClinicalTrials.gov More Solid Tumours trials

Plain-language summary

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Exclusion criteria

✕. All known lesions were previously treated with surgery or stereotactic surgery (whole-brain radiation is not allowed unless given after definitive treatment with surgery or stereotactic surgery) AND
✕. Brain lesion(s), if still present, must be confirmed stable (i.e., no increase in lesion size) for \>= 6 weeks prior to randomization (stability must be confirmed with two consecutive magnetic resonance image (MRI) or computed tomography (CT) scans with contrast, AND
✕. Asymptomatic with no corticosteroid requirements for \>= 4 weeks prior to randomization, AND
✕. No enzyme inducing anticonvulsants for \>= 4 weeks prior to randomization
✕. LVEF \< LLN for the institution
✕. A corrected QT interval \>=480 msec (e.g. Bazett's formula \[QTcB\])
✕. A history or evidence of current clinically significant uncontrolled arrhythmias (exception: subjects with controlled atrial fibrillation for \> 30 days prior to randomization are eligible)
✕. A history (within 6 months prior to first dose of study treatment) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty

What they're measuring

Number of subjects with Adverse Events (AEs) to assess the safety of dabrafenib +/- trametinib when administered in combination with ipilimumab

Timeframe: Follow-up up to 6 months after last subject last dose

Changes in laboratory values, vital signs, and physical examinations as a measure of safety of dabrafenib +/- trametinib when administered in combination with ipilimumab

Timeframe: Follow-up up to 6 months after last subject last dose