NCT04527549|TerminatedPhase 2ResultsDMCFDA Drug

Study Stopped

Slow accrual

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

The BAMM2 (BRAF, Autophagy, MEK Inhibition in Melanoma) Study: A Randomized Double Blind Phase II Study of Dabrafenib and Trametinib With or Without Hydroxychloroquine in Advanced BRAF V600E/K Melanoma With Elevated LDH

ECOG-ACRIN Cancer Research Group ClinicalTrials.gov

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3 other identifiers

EA6191NCI-2020-04552U10CA180820

Study Type

interventional

Target

Locations

1 country

Sites

199

Timeline

RegisteredAug 2020

StartedJun 2021

CompletionJan 2024

Brief Summary

This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. Hydroxychloroquine may cause cell death in tumor cells that rely on a process called "autophagy" for survival. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with dabrafenib and trametinib may work better than dabrafenib and trametinib alone to shrink and stabilize the cancer.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_2

Timeline

Completed

Started Jun 2021

Geographic Reach

1 country

199 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

2.6 years study duration

First Submitted

Initial submission to the registry

August 24, 2020

Completed

2 days until next milestone

First Posted

Study publicly available on registry

August 26, 2020

Completed

9 months until next milestone

Study Start

First participant enrolled

June 1, 2021

Completed

2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 8, 2024

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 8, 2024

Completed

8 months until next milestone

Results Posted

Study results publicly available

August 22, 2024

Completed

Last Updated

June 1, 2026

Status Verified

May 1, 2026

Enrollment Period

2.6 years

First QC Date

August 24, 2020

Results QC Date

July 9, 2024

Last Update Submit

May 12, 2026

Conditions

Pathologic Stage IV Cutaneous Melanoma AJCC v8 Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 Locally Advanced Melanoma Unresectable Melanoma Clinical Stage IV Cutaneous Melanoma AJCC v8

Outcome Measures

Primary Outcomes (1)

One-year Progression-free Survival Rate
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.
Assessed every 2 months until 6 months after completion of study treatment, up to 1 year

Secondary Outcomes (5)

Progression-free Survival
Assessed every 2 months until 6 months after completion of study treatment, up to 3 years
Proportion of Patients With Best Overall Response
Assessed every 2 months until 6 months after completion of study treatment, up to 3 years
Proportion of Patients With Complete Response
Assessed every 2 months until 6 months after completion of study treatment, up to 3 years
Adverse Event Rate
Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 3 years
Overall Survival
Assessed every 2 months until 6 months after completion of study treatment, up to 3 years

Study Arms (2)

Arm A (dabrafenib, trametinib, hydroxychloroquine)

EXPERIMENTAL

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.

Drug: Dabrafenib mesylateDrug: HydroxychloroquineDrug: Trametinib dimethyl sulfoxide

Arm B (dabrafenib, trametinib, placebo)

ACTIVE COMPARATOR

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.

Drug: Dabrafenib mesylateDrug: Placebo AdministrationDrug: Trametinib dimethyl sulfoxide

Interventions

HydroxychloroquineDRUG

Given PO

Also known as: Hydroxychloroquine sulfate, Plaquenil

Arm A (dabrafenib, trametinib, hydroxychloroquine)

Placebo AdministrationDRUG

Given PO

Arm B (dabrafenib, trametinib, placebo)

Trametinib dimethyl sulfoxideDRUG

Given PO

Also known as: trametinib, GSK1120212B, TMT212-NXA, JTP-74057, JTP-78296, JTP-75303, Mekinist®, NSC 763093

Arm A (dabrafenib, trametinib, hydroxychloroquine)Arm B (dabrafenib, trametinib, placebo)

Dabrafenib mesylateDRUG

Given PO

Also known as: NSC 763760, GSK2118436A (free base), Tafinlar®, GSK2118436B

Arm A (dabrafenib, trametinib, hydroxychloroquine)Arm B (dabrafenib, trametinib, placebo)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patient must have locally advanced unresectable stage IIIC or stage IV melanoma
Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay
Patient must have serum LDH \> Upper limit of normal per institution standards
Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Baseline measurements of sites of disease must be obtained within 3 weeks prior to study randomization
Patient must have been treated with prior immune checkpoint inhibitor therapy (anti PD-1 antibody, anti-CTLA-4 antibody or a combination regimen including either or both agents) either in the adjuvant or metastatic setting. Patient may have received investigational agents in combination with standard therapy, as long as it was adhering to the timeframes below
Patient must have discontinued active immunotherapy (IL-2, interferon, anti-CTLA-4 antibody, anti-PD-1 antibody etc.) or chemotherapy at least 4 weeks prior to randomization
Patient must have discontinued any oral targeted therapy at least 2 weeks prior to randomization
Patient may have been treated with prior adjuvant therapy including combined BRAF and MEK inhibitor therapy. Patients will be eligible if they tolerated this therapy and did not discontinue the therapy due to toxicity AND \>= 6 months have elapsed since the end of adjuvant BRAF and MEK inhibition.
Patient may have been treated with prior chemotherapy or radiation therapy
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or abstaining from sexual intercourse for the duration of their participation in the study and for 4 months after the last dose of protocol treatment
Patient must have recovered from clinically significant reversible toxicities from previous treatment prior to randomization. Abnormal laboratory values may be grade 1, as long as they meet the eligibility criteria for organ and marrow function
Patient must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
+11 more criteria

You may not qualify if:

Receiving any other investigational anticancer therapy during the period on study or the 4 weeks prior to randomization
Patients received BRAF and MEK inhibitor therapy in the metastatic setting
Patients who are experiencing an objective partial response to immunotherapy at the time of study enrollment
Pregnant or breast-feeding; due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
A history of interstitial lung disease (ILD) or chronic pneumonitis
NOTE: If there is radiographic evidence of ILD that is clinically insignificant and asymptomatic, the patient would be eligible
Porphyria or psoriasis due to risk of disease exacerbation unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
Previously documented retinal vein occlusion
A history or evidence of increased cardiovascular risk including:
Left ventricular ejection fraction (LVEF) \< institutional lower limit of normal measured within 14 days prior to randomization
A QT interval corrected for heart rate using the Bazett's formula \>= 480 msec
Current clinically significant uncontrolled arrhythmias. Exception: Patients with controlled atrial fibrillation for \> 30 days prior to randomization are eligible
Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization
Abnormal cardiac valve morphology (\>= grade 2) documented by echocardiogram unless a cardiologist concludes the valve abnormality is not clinically significant. Patients with grade 1 abnormalities (i.e., mild regurgitation/stenosis) are eligible
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
+5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

ECOG-ACRIN Cancer Research Grouplead
National Cancer Institute (NCI)collaborator

Study Sites (199)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC