NCT01940809.

Study name	Ipilimumab with or without dabrafenib, trametinib, and/or nivolumab in treating patients with melanoma that is metastatic or cannot be removed by surgery
Methods	Phase I RCT.
Participants	Metastatic melanoma. Estimated enrolment: 40.
Interventions	Five‐arm trial: participants receive dabrafenib orally twice daily and trametinib orally once daily for 25 days. Participants then receive ipilimumab IV over 90 minutes. Treatment with ipilimumab repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity; participants receive dabrafenib orally twice daily and trametinib orally once daily for 25 days followed by nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses, followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses; participants receive trametinib orally once daily for 25 days. Participants then receive ipilimumab IV over 90 minutes. Treatment with ipilimumab repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity; participants receive trametinib orally once daily for 25 days followed by nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses, followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses; participants receive dabrafenib orally twice daily for 25 days. Participants then receive ipilimumab IV over 90 minutes. Treatment with ipilimumab repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity; participants receive dabrafenib orally twice daily for 25 days followed by nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses, followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses; participants receive ipilimumab IV over 90 minutes. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Participants receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes every 3 weeks for 4 doses, followed by nivolumab monotherapy IV every 2 weeks continuously for up to 42 courses.
Outcomes	Primary outcome: Incidence of grade 3 or higher immune‐related adverse events. Secondary outcomes: disease‐control rate; proportion of participants receiving dabrafenib and trametinib with grade 3 or higher irAEs after disease progression on ipilimumab; and response rate for the total treatment period.
Starting date	August 2013.
Contact information	Brigham and Women's Hospital, Boston, MA, USA. Contact: Scott J Rodig, srodig@partners.org; Dana‐Farber Cancer Institute, Boston, MA, USA. Contact: Patrick A Ott, Patrick_ott@dfci.harvard.edu.
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