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Clinical Trials in Norway / NCT02196181
Active, not recruiting Phase 2

Testing Two Different Treatment Schedules of Dabrafenib and Trametinib for Skin Cancer Which Has Spread

NCT02196181 · tracked via the Priya Life Science Norway tracker
Phase
Phase 2
Started
2014-09-19
Last updated
2026-09-15

Condition(s) studied

Stage III Cutaneous Melanoma AJCC v7Stage IV Cutaneous Melanoma AJCC v6 and v7Unresectable Melanoma

Investigational drug(s) / intervention(s)

Biospecimen CollectionComputed TomographyDabrafenib Mesylate →Echocardiography TestMultigated Acquisition ScanPositron Emission TomographyTrametinib Dimethyl Sulfoxide →

Biospecimen Collection: Undergo blood sample collection

Computed Tomography: Undergo CT or PET/CT

Dabrafenib Mesylate: Given PO

Echocardiography Test: Undergo ECHO

Multigated Acquisition Scan: Undergo MUGA

Positron Emission Tomography: Undergo PET/CT

Trametinib Dimethyl Sulfoxide: Given PO

Study summary

This phase II trial compares the effect of dabrafenib and trametinib given continuously to given with a break in treatment (intermittent) in treating patients with stage III-IV melanoma that cannot be removed by surgery and contains a B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dabrafenib and trametinib with intermittent dosing may be as effect as when given continuously in treating patients with stage III-IV melanoma with a BRAF mutation that cannot be removed by surgery.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: * STEP 1: REGISTRATION * Patients must have histologically or cytologically confirmed stage IV or unresectable stage III BRAF V600E or BRAF V600K mutant melanoma * Patients must have BRAF V600E or BRAF V600K mutation identified by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; acceptable analytic techniques include but are not restricted to DNA sequencing, pyrosequencing, polymerase chain reaction (PCR), melting point assays, and immunohistochemistry * Contrast-enhanced CT scans of the neck, chest, abdomen and pelvis are required; a whole body PET/CT scan with diagnostic quality images and intravenous iodinated contrast may be used in lieu of a contrast enhanced CT of the neck, chest, abdomen and pelvis; contrast may be omitted if the treating investigator believes that exposure to contrast poses an excessive risk to the patient; patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; all measurable lesions must be assessed within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1) * Patients must not have received a prior BRAF or MEK inhibitor * Patients with a history of brain metastases are eligible if the patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 7 days prior to registration * Patients must not have received any anti-cancer drug within 28 days prior to registration, and must not have received any nitrosoureas or mitomycin C within 42 days prior to registration * Patients must not have received any major surgery or immunotherapy within 28 days prior to registration * Patients must not have any unresolved toxicity greater than National Cancer Institute (NCI)-CTCAE version (v) 4.0 grade 1 from previous anti-cancer therapy except alopecia within 7 days prior to registration * Patients must be age \>= 18 years of age * Absolute neutrophil count (ANC) \>= 1,200/ul (obtained within 28 days prior to registration) * Platelets \>= 100,000/ul (obtained within 28 days prior to registration) * Hemoglobin \>= 9 g/dL (obtained within 28 days prior to registration) * Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (or =\< 2.5 x upper limit of normal \[ULN\] with Gilbert's syndrome) (obtained within 28 days prior to registration) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x IULN (or \< 5 x IULN for patients with known liver metastases) (obtained within 28 days prior to registration) * Serum albumin \>= 2.5 g/dL (obtained within 28 days prior to registration) * Serum creatinine =\< 1.5 mg/dL OR measured or calculated creatinine clearance \>= 50 mL/min; creatinine measurements must be obtained within 28 days prior to registration * Patients must have lactate dehydrogenase (LDH) obtained within 28 days prior to registration in order to obtain baseline stratification information * Patients must have a left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal (ILLN) by ECHO or MUGA within 28 days prior to registration * Patients must have corrected QT (QTc) =\< 480 msec by electrocardiogram (ECG) (corrected using the Bazett's formula) within 28 days prior to registration * Patients with known history or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible: * History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes) * Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as: * Evidence of new optic disc cupping * Evidence of new visual field defects * Intraocular pressure \> 21 mmHg * NOTE: ophthalmic exam is required for all patients; exam must be obtained within 28 days prior to registration * Patients must be able to take oral medications; patients must not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of protocol treatment (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) * Patients receiving anticoagulation treatment are allowed to participate with international normalized ratio (INR) established within the therapeutic range * Patients must not have a history of pneumonitis or interstitial lung disease * Patients must not have any grade II/III/IV cardiac disease as defined by the New York Heart Association criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia; abnormal cardiac valve morphology (\>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities \[i.e., mild regurgitation/stenosis\]) can be entered on study; patients with a history of atrial fibrillation must have atrial fibrillation controlled for at least 30 days prior to registration * Patients with known hepatitis B or hepatitis C are not eligible, regardless of concomitant antiretroviral therapy or current viral load * Patients with known human immunodeficiency virus (HIV) may be eligible providing they meet the following additional criteria: * Cluster of differentiation (CD)4 cells \>= 500/uL * Serum HIV viral load of \< 25,000 IU/ml * No current antiretroviral therapy * Tests must be obtained within 28 days prior to registration; patients who are HIV positive (+) and do not meet all of these criteria are not eligible for this study (HIV/hepatitis testing are not required for patients without known infection) * Pre-study history and physical must be obtained with 28 days prior to registration * Patients must have dermatology exam obtained within 28 days prior to registration to obtain baseline measurement; exam to be performed by treating physician or designated dermatologist * Patients must have Zubrod performance status of 0, 1 or 2 * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years; exception: patients with known history of colon cancer, cancer of the pancreas, or any cancer known to harbor an activating RAS mutation are ineligible regardless of stage or time since diagnosis * Patients must not be pregnant or nursing because of the risk of fetal harm; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures; hormonal contraception is not allowed due to drug interactions which can render hormonal contraceptives ineffective * Patients must be offered the opportunity to participate in specimen banking * Patients with cutaneous or superficial lesions that do not require imaging guidance for biopsy must be willing to undergo biopsies for tissue submission and blood draws for translational medicine * Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * STEP 2: RANDOMIZATION * After completing one cycle of therapy, patients will be registered for randomization between intermittent and continuous dosing, provided that they were eligible for the initial step 1 registration and satisfy the following criteria * Patients must not have unequivocal disease progression (by RECIST v1.1) during the first cycle; patients must have disease assessed using the same method as baseline within +/- 5 days of the day 56 scheduled assessment (between days 51-55 of cycle 1, or days 1-5 of cycle 2); all disease must be assessed and documented on the follow-up tumor assessment form (RECIST 1.1) * Patients must be registered to step 2: randomization within +/- 5 days of starting cycle 2; patients MUST NOT be registered prior to the day 56 disease assessment

Primary outcome measure(s)

Trial sites (752)

FacilityCityRegionStatus
University of Alabama at Birmingham Cancer Center Birmingham Alabama
Anchorage Associates in Radiation Medicine Anchorage Alaska
Anchorage Radiation Therapy Center Anchorage Alaska
Alaska Breast Care and Surgery LLC Anchorage Alaska
Alaska Oncology and Hematology LLC Anchorage Alaska
Alaska Regional Hospital Anchorage Alaska
Alaska Women's Cancer Care Anchorage Alaska
Anchorage Oncology Centre Anchorage Alaska
Katmai Oncology Group Anchorage Alaska
Providence Alaska Medical Center Anchorage Alaska
Fairbanks Memorial Hospital Fairbanks Alaska
Banner University Medical Center - Tucson Tucson Arizona
University of Arizona Cancer Center-North Campus Tucson Arizona
Onvida Health Yuma Medical Center Yuma Arizona
Mercy Hospital Fort Smith Fort Smith Arkansas
CHI Saint Vincent Cancer Center Hot Springs Hot Springs Arkansas
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro Jonesboro Arkansas
John L McClellan Memorial Veterans Hospital Little Rock Arkansas
University of Arkansas for Medical Sciences Little Rock Arkansas
Highlands Oncology Group - Rogers Rogers Arkansas
Kaiser Permanente-Anaheim Anaheim California
Kaiser Permanente-Deer Valley Medical Center Antioch California
PCR Oncology Arroyo Grande California
Kaiser Permanente-Baldwin Park Baldwin Park California
Kaiser Permanente-Bellflower Bellflower California
Providence Saint Joseph Medical Center/Disney Family Cancer Center Burbank California
Epic Care-Dublin Dublin California
Bay Area Breast Surgeons Inc Emeryville California
Epic Care Partners in Cancer Care Emeryville California
Kaiser Permanente-Fontana Fontana California
Kaiser Permanente-Fremont Fremont California
Kaiser Permanente-Fresno Fresno California
Kaiser Permanente South Bay Harbor City California
Kaiser Permanente-Irvine Irvine California
Loma Linda University Medical Center Loma Linda California
Kaiser Permanente Los Angeles Medical Center Los Angeles California
Kaiser Permanente West Los Angeles Los Angeles California
UCLA / Jonsson Comprehensive Cancer Center Los Angeles California
Contra Costa Regional Medical Center Martinez California
Kaiser Permanente-Modesto Modesto California

+ 712 more sites — see the full list on the official registry below.

More National Cancer Institute (NCI) trials in Norway

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT02196181 on ClinicalTrials.gov ↗ ← All trials in Norway