Trial Outcomes & Findings for Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma (NCT NCT04527549)

Last Updated: 2025-11-12

Results Overview

Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. One-year progression-free survival rate is estimated from the Kaplan-Meier progression-free survival curve.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Assessed every 2 months until 6 months after completion of study treatment, up to 1 year

Results posted on

2025-11-12

Participant Flow

This study was activated on October 23, 2020, and closed to accrual on March 1, 2023 due to slower than expected accrual. The first patient was enrolled on June 1st, 2021.

Participant milestones

Participant milestones
Measure	Arm A (dabrafenib, trametinib, hydroxychloroquine) Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (dabrafenib, trametinib, placebo) Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	3	2
Overall Study COMPLETED	2	1
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (dabrafenib, trametinib, hydroxychloroquine) Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (dabrafenib, trametinib, placebo) Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Dabrafenib, Trametinib, Hydroxychloroquine) n=3 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (Dabrafenib, Trametinib, Placebo) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Total n=5 Participants Total of all reporting groups
Age, Continuous	38 years n=10 Participants	68 years n=10 Participants	61 years n=20 Participants
Sex: Female, Male Female	2 Participants n=10 Participants	1 Participants n=10 Participants	3 Participants n=20 Participants
Sex: Female, Male Male	1 Participants n=10 Participants	1 Participants n=10 Participants	2 Participants n=20 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=10 Participants	2 Participants n=10 Participants	5 Participants n=20 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) Asian	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) Black or African American	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) White	3 Participants n=10 Participants	2 Participants n=10 Participants	5 Participants n=20 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants

PRIMARY outcome

Timeframe: Assessed every 2 months until 6 months after completion of study treatment, up to 1 year

Population: Only patients who received treatment were included in the analysis.

Outcome measures

Outcome measures
Measure	Arm A (dabrafenib, trametinib, hydroxychloroquine) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (dabrafenib, trametinib, placebo) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
One-year Progression-free Survival Rate	0.5 proportion of participants Interval 0.006 to 0.91	NA proportion of participants 1-year PFS rate could not be estimated as one patient experienced progression within 1 year and the other patient withdrew consent prior to 1 year.

SECONDARY outcome

Timeframe: Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

Population: Only patients received treatment were included in the analysis.

Outcome measures

Outcome measures
Measure	Arm A (dabrafenib, trametinib, hydroxychloroquine) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (dabrafenib, trametinib, placebo) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	12.5 months Interval 7.0 to 18.0	NA months Interval 2.0 to Median was not reached. The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

Population: Only patients received treatment were included in the analysis.

Best overall response is defined as either complete response or partial response. Complete response is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as persistence of one or more non-target lesion(s) and at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Arm A (dabrafenib, trametinib, hydroxychloroquine) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (dabrafenib, trametinib, placebo) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Best Overall Response	1.0 proportion of participants Interval 0.16 to 1.0	0.5 proportion of participants Interval 0.01 to 0.99

SECONDARY outcome

Timeframe: Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

Population: Only patients received treatment were included in the analysis.

Complete response is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

Outcome measures

Outcome measures
Measure	Arm A (dabrafenib, trametinib, hydroxychloroquine) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (dabrafenib, trametinib, placebo) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Complete Response	0 proportion of participants Interval 0.0 to 0.84	0 proportion of participants Interval 0.0 to 0.84

SECONDARY outcome

Timeframe: Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years

Population: Only patients who received treatment were included in this analysis.

Proportion of patients with treatment-related adverse events of grade 3 or higher.

Outcome measures

Outcome measures
Measure	Arm A (dabrafenib, trametinib, hydroxychloroquine) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (dabrafenib, trametinib, placebo) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Adverse Event Rate	0.5 proportion of participants Interval 0.01 to 0.99	0.5 proportion of participants Interval 0.01 to 0.99

SECONDARY outcome

Timeframe: Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

Population: Only patients received treatment were included in the analysis.

Overall survival is defined as the time from randomization to death or date last known alive.

Outcome measures

Outcome measures
Measure	Arm A (dabrafenib, trametinib, hydroxychloroquine) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (dabrafenib, trametinib, placebo) n=2 Participants Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Survival	NA months Median was not reached. The lower and upper limit of the 95% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment.	NA months Interval 2.0 to Median was not reached. The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

Adverse Events

Arm A (dabrafenib, trametinib, hydroxychloroquine)

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Arm B (dabrafenib, trametinib, placebo)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Arm A (dabrafenib, trametinib, hydroxychloroquine) n=2 participants at risk Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Arm B (dabrafenib, trametinib, placebo) n=2 participants at risk Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
General disorders Fever	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years Only patients who received treatment are included in this analysis.	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years Only patients who received treatment are included in this analysis.
Skin and subcutaneous tissue disorders Rash maculo-papular	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years Only patients who received treatment are included in this analysis.	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years Only patients who received treatment are included in this analysis.
Vascular disorders Arterial thromboembolism	0.00% 0/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years Only patients who received treatment are included in this analysis.	50.0% 1/2 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years Only patients who received treatment are included in this analysis.

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60