Molecularly Targeted Therapy in Treating Patients With BRAF Wild-type Melanoma That is Metastatic

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02094872
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 49
• Locations: 8
• Arm: 1
• Duration (Months): 55
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well molecularly targeted therapy works in treating patients with melanoma that has spread to other parts of the body. Patients must have received or do not qualify for prior immunotherapy. Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. Molecularly targeted therapy works by treating patients with substances that kill cancer cells by targeting key molecules involved in cancer cell growth.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma	Other: cytology specimen collection procedure; Drug: MEK 162 therapy or molecularly targeted therapy; Procedure: therapeutic procedure; Other: laboratory biomarker analysis; Other: quality-of-life assessment	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the difference in best overall response rate (BORR) between patients treated with MEK162 following personalized molecularly guided assignment vs. a historical BORR of 7% in this patient population.

SECONDARY OBJECTIVES:

1. To evaluate the safety of performing individualized drug therapy (including novel agents and commercially-available agents) in the context of a personalized medicine clinical trial.

2. To define the difference in progression free survival (PFS) between patients treated with MEK162 following personalized molecularly guided assignment vs. a historical PFS rate of 2 months in this patient population.

3. To continually assess data in real time so as to iteratively refine and standardize a set of statistical and informatics methodologies for matching treatments to the patient's tumor, based on the molecular profile.

OUTLINE:

Patients undergo collection of tissue and blood samples for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Stand Up to Cancer Consortium Genomics-Enabled Medicine for Melanoma (G.E.M.M.): Using Molecularly-Guided Therapy for Patients With BRAF Wild-Type (BRAFwt) Metastatic Melanoma
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm I (molecularly targeted therapy) Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

Other: cytology specimen collection procedure; Undergo collection of tissue and blood samples; Other Names: cytologic sampling ; Drug: MEK 162 therapy or molecularly targeted therapy; molecularly targeted therapy, MEK 162 therapy; Procedure: therapeutic procedure; Other Names: Therapeutic Interventions Therapeutic Method Therapeutic Technique Therapy TX ; Other: laboratory biomarker analysis; Correlative studies; Other: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment

Outcome Measures

Primary Outcome Measures

1. Best Overall Response Rate (BORR) [Up to 1 year]

   The best overall response rate (BORR) was assessed up to 1 year.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year]

   A log rank test will be performed for the comparison between the two groups.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient with metastatic or locally advanced and unresectable BRAF wild-type melanoma who have either progressed following previous treatment of immunotherapy, or are not eligible for immunotherapy; pts. are defined as "BRAF wild-type" if they test negative for V600 mutations based on a Clinical Laboratory Improvement Amendments (CLIA) certified assay

• Patients must have tumor accessible by interventional radiology or surgical intervention and suitable for biopsy (BX) with 5-6 passes of a 16 or 18 gauge needle for core BX (defined as at least 1 cm^3 tumor/50 mg accessible for BX), and must agree to undergo up to two surgical resections/biopsies to collect tumor for research purposes; the first of these biopsies will occur at the beginning of the study, prior to genetic analysis and Rx; the second BX will be performed at the time of DZ progression/end of study should funding be available

• Patients must have measurable DZ (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 [v1.1] criteria), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam; for lymph nodes, the short axis must be >= 15 mm

• Previous therapies: prior radiation therapies, immunotherapies, and investigational therapies are allowed as follows.

• Radiation: prior radiation therapy (RT) is allowed with the following conditions:

• Patients who have received minimal RT (=< 5% of their total marrow volume) must have completed it >= 2 weeks prior to the initiation of study Rx

• Patients who have received RT that constituted > 5% but < 50% of their total marrow volume must have completed it >= 4 weeks prior to the initiation of study treatment

• Patients who have received prior radiation to 50% or more of their total marrow volume will be excluded

• Patients may be biopsied while undergoing RT as long as BX site is not in the radiation portal; however, they still have to wait the required amount of time from radiation to treatment even though the tumor board may have already occurred and a treatment plan assigned

• Other therapies: prior investigational or targeted therapies and immunotherapies may be allowed following discussion with the PI (PI); if the PI deems the prior treatment acceptable, patients must not have received these therapies for 28 days or five half-lives of the drug (whichever is lesser) prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies; prior therapy with mitogen-activated protein kinase (MEK) inhibitors will not be allowed

• Patients with chronic grade 2 toxicity may be eligible at the discretion of the PI if the condition has been stable, and not worsening, for at least 30 days; pts. with ongoing alopecia of any grade will be eligible

• Patient must have a life expectancy of >= 3 months, as estimated by the treating oncologist

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Hemoglobin >= 9 g/dL

• Leukocytes >= 3,000/microliter (mcL)

• Absolute neutrophil count (ANC) >= 1,500/mcL

• Platelets (PLT) >= 100,000/mcL

• Aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN); if liver metastases are present, =< 5 x ULN

• Alanine aminotransferase (ALT) =< 2.5 x ULN; if liver metastases are present, =< 5 x ULN

• Bilirubin =< 1.5 x ULN

• Creatinine =< 1.5 x ULN OR calculated or measured creatinine clearance >= 50 mL/min/1.73 m^2 for pts. with creatinine above institutional normal

• If available, pt. must agree to provide archival tissue for research purposes (either archival paraffin tissue block or 10 unstained slides of a primary or metastatic melanoma lesion) prior to enrollment; samples should be shipped within 1 month after enrollment

• Patient agrees to having a blood sample (a minimum of 10 mL, with 20 mL preferred) drawn and analyzed to compare their normal genetic profile to that of their tumor sample

• Patient must be able to tolerate oral medication

• Women of child-bearing potential and men must agree to use 2 forms of adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for four months following completion of study therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; women who become pregnant must immediately discontinue Rx with any study therapy; male pts. should avoid impregnating a female partner; male pts., even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study Rx period and through 4 months after the last dose of study drug, or completely abstain from sexual intercourse

• Patient must have the ability to understand and the willingness to sign a written informed consent document

• Patient must be willing and able to comply with the protocol for the duration of the study, including attending scheduled visits, examinations, the BX procedure, and having their tumor and blood molecularly characterized

• Patient understands they must meet all inclusion and exclusion criteria in the drug specific appendix for which they were assigned.

Exclusion Criteria:

• Patients with peripheral neuropathy >= grade 2 are not permitted unless discussed with the PI and only in unique circumstances (i.e. unilateral neuropathy due to trauma)

• Patient has DZ that tests positive for BRAF V600 mutations based on the results of a CLIA certified assay

• Patients with active infection at time of BX

• Patients with any evidence of severe or uncontrolled systemic DZ(s) including known cases of hepatitis B or C or human immunodeficiency virus (HIV); screening for chronic conditions is not required, although pts. known to have such conditions at screening should not be included

• Any patient requiring chronic maintenance of red blood cell, white blood cell or granulocyte counts through the use of blood transfusions or growth factor support (e.g. Neulasta®, Neupogen®)

• Patients with a prior history of seizures within the past year unrelated to brain metastases

• Patients with known active progressive brain metastases; pts. with prior treated brain metastases are allowed, providing that they were not accompanied by seizures within the past year and that a baseline brain MRI scan prior to study entry demonstrates no current evidence of active brain metastases; all pts. with prior treated brain metastases must be stable for > 1 months after treatment and off steroid treatment prior to study enrollment

• Patients receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (i.e. megestrol acetate, bisphosphonates); these medications must have been started >= month prior to enrollment on this study; pts. may be on low molecular weight heparin or direct factor Xa inhibitors

• Patients with any clinically significant medical condition which, in the opinion of the investigator, makes it undesirable for the pt. to participate in the study or which could jeopardize compliance with protocol requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations

• Patients with preexisting cardiac conditions, including uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure will not be eligible

• Patients with left ventricular ejection fraction (LVEF) < 45% will not be eligible

• Patients with either of the following within 6 months before the first dose of study treatment:

• Stroke (including transient ischemic attack [TIA], or other ischemic event)

• Myocardial infarction

• Patients with acute gastrointestinal bleeding within 1 month of study entry

• Patients who have, at screening, corrected QT interval using Fridericia's formula (QTcF) >= 450 msec for males and QTcF >= 470 for females

• Patients with a co-morbid condition(s) that, in the opinion of the investigator, prevents safe surgery/BX procedure

• Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption or ability to swallow oral medication

• Pregnant or nursing women; breastfeeding must be discontinued prior to Rx

• Patients who have received organ transplant

• Patients who have had major surgery within 14 days of study enrollment

• Patients diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, or an in situ malignancy. Patients with a low grade prostate cancer, not on hormonal therapy, for which the disease is confined to the prostate may be considered eligible by the overall Principal Investigator on a case by case basis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Cancer Center	Scottsdale	Arizona	United States	85259-5499
2	Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut	United States	06520-8028
3	Mayo Clinic Cancer Center	Jacksonville	Florida	United States	32224
4	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0944
5	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
6	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
7	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37240
8	Baylor Sammons Cancer Center	Dallas	Texas	United States	75246

Sponsors and Collaborators

• Yale University
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Patricia LoRusso, D.O., Yale University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 21, 2016

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02094872
• Other Study ID Numbers: 1408014446; NCI-2014-00670; WIRB Pro #20140190; WO #1-822810-1; Invest #161467; Study #1144561; 2013-184; P30CA022453
• First Posted: Mar 24, 2014
• Last Update Posted: Jan 2, 2020
• Last Verified: Dec 1, 2019

• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Recruitment Details	Based on the initial 23 patients enrolled on this study who underwent molecular profiling and tumor board evaluation, 20 were assigned MEK162 by the tumor board. Patients not assigned MEK162 still received their assigned treatment, but were not considered evaluable for the primary endpoint.

Arm/Group Title	Arm I (Molecularly Targeted Therapy)
Arm/Group Description	Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. cytology specimen collection procedure: Undergo collection of tissue and blood samples MEK 162 therapy or molecularly targeted therapy: molecularly targeted therapy, MEK 162 therapy therapeutic procedure laboratory biomarker analysis: Correlative studies quality-of-life assessment: Ancillary studies
Period Title: Overall Study
STARTED	49
Received Biopsy	37
Received Tumor-board Recommendation	36
Received Targeted Therapy	20
Received Standard of Care	9
Patients Treated With MEK162	20
COMPLETED	20
NOT COMPLETED	29

Baseline Characteristics

Arm/Group Title	Arm I (Molecularly Targeted Therapy)
Arm/Group Description	Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. cytology specimen collection procedure: Undergo collection of tissue and blood samples MEK 162 therapy or molecularly targeted therapy: molecularly targeted therapy, MEK 162 therapy therapeutic procedure laboratory biomarker analysis: Correlative studies quality-of-life assessment: Ancillary studies
Overall Participants	49
Age, Customized (Count of Participants)
30-39	1 2%
40-49	6 12.2%
50-59	10 20.4%
60-69	13 26.5%
70-79	15 30.6%
80-89	4 8.2%
Sex: Female, Male (Count of Participants)
Female	23 46.9%
Male	26 53.1%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaskan Native	0 0%
Asian or Pacific Islander	0 0%
Black, not of Hispanic Origin	2 4.1%
Hispanic	6 12.2%
White, not of Hispanic Origin	43 87.8%
Other/	4 8.2%
Region of Enrollment (participants) [Number]
United States	49 100%

Outcome Measures

1. Primary Outcome

Title	Best Overall Response Rate (BORR)
Description	The best overall response rate (BORR) was assessed up to 1 year.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Molecularly Targeted Therapy)
Arm/Group Description	Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. cytology specimen collection procedure: Undergo collection of tissue and blood samples MEK 162 therapy or molecularly targeted therapy: molecularly targeted therapy, MEK 162 therapy therapeutic procedure laboratory biomarker analysis: Correlative studies quality-of-life assessment: Ancillary studies
Measure Participants	20
Progressive Disease	2 4.1%
Stable Disease	17 34.7%
Partial Response	1 2%

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	A log rank test will be performed for the comparison between the two groups.
Time Frame	From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year

Outcome Measure Data

Analysis Population Description

Given the lack of response in this study and the decision to terminate it early, no data for PFS data were collected or analyzed. In addition, with the study amendment removing the second arm, this analysis would not have been possible to conduct.

Arm/Group Title	Arm I (Molecularly Targeted Therapy)
Arm/Group Description	Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. cytology specimen collection procedure: Undergo collection of tissue and blood samples MEK 162 therapy or molecularly targeted therapy: molecularly targeted therapy, MEK 162 therapy therapeutic procedure laboratory biomarker analysis: Correlative studies quality-of-life assessment: Ancillary studies
Measure Participants	0

Adverse Events

Time Frame	1 year
Arm/Group Title	Arm I (Molecularly Targeted Therapy)
Arm/Group Description	Patients undergo collection of tissue and blood samples for DNA and RNA analysis via sequencing. Based on the results of the DNA and RNA analysis, patients receive molecularly targeted therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. cytology specimen collection procedure: Undergo collection of tissue and blood samples MEK 162 therapy or molecularly targeted therapy: molecularly targeted therapy, MEK 162 therapy therapeutic procedure laboratory biomarker analysis: Correlative studies quality-of-life assessment: Ancillary studies
All Cause Mortality
	Arm I (Molecularly Targeted Therapy)
	Affected / at Risk (%)	# Events
Total	5/49 (10.2%)
Serious Adverse Events
	Arm I (Molecularly Targeted Therapy)
	Affected / at Risk (%)	# Events
Total	48/49 (98%)
Blood and lymphatic system disorders
Hospitalized for anemia	1/49 (2%)
Thrombocytopenia	1/49 (2%)
Gastrointestinal disorders
Hospitalized for Nausea and vomiting	1/49 (2%)
Anemia due to gastric hemorrhage	1/49 (2%)
Hospitalized for abdominal and back pain	1/49 (2%)
General disorders
Generalized Weakness	1/49 (2%)
Fatigue	2/49 (4.1%)
Weakness and fatigue	1/49 (2%)
Hospitalized for generalized weakness	1/49 (2%)
Generalized weakness requiring hospitalization; outcome death	1/49 (2%)
Hepatobiliary disorders
Hepatic Failure (patient never received drug)	1/49 (2%)
Immune system disorders
Anaphylactic reaction to taxol, hospitalized	1/49 (2%)
Allergic reaction to Augmentin; Acute kidney Injury (patient never received drug)	1/49 (2%)
Infections and infestations
Hospitalized for UTI	1/49 (2%)
Enterocolitis infectious (Clostridium difficile)	1/49 (2%)
Hospitalized for fever	1/49 (2%)
Strep B sepsis	1/49 (2%)
Metabolism and nutrition disorders
Hyponatremia	4/49 (8.2%)
Hypochloridemia	1/49 (2%)
Musculoskeletal and connective tissue disorders
Dropped Head Syndrome	1/49 (2%)
Ocular muscle weakness	1/49 (2%)
Hospitalized for back pain	1/49 (2%)
Nervous system disorders
Hospitalized for chronic intractable pain	1/49 (2%)
Headache	1/49 (2%)
Hospitalization for neurological symptoms: brain metastasis	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Hospitalized for pneumonitis	1/49 (2%)
Hospitalized for pneumonia, sepsis, outcome death	1/49 (2%)
Skin and subcutaneous tissue disorders
Acneiform rash	1/49 (2%)
Elevated alkaline phosphatase	1/49 (2%)
Elevated aspartate aminotransferase	3/49 (6.1%)
Elevated alanine aminotransferase	1/49 (2%)
Transaminitis	1/49 (2%)
Creatine phosphokinase elevation	2/49 (4.1%)
Uric acid elevations	1/49 (2%)
Surgical and medical procedures
Radical resection of malignant soft tissue tumor (melanoma) on back	1/49 (2%)
Vascular disorders
Hospitalized for hypotension related to adrenal insufficiency	1/49 (2%)
Hospitalized for hypotension	1/49 (2%)
Hypertension	1/49 (2%)
Hospitalized for pulmonary embolism	3/49 (6.1%)
Hypotensive, AKI (patient never received drug)	1/49 (2%)
Other (Not Including Serious) Adverse Events
	Arm I (Molecularly Targeted Therapy)
	Affected / at Risk (%)	# Events
Total	32/49 (65.3%)
Blood and lymphatic system disorders
Anemia	11/49 (22.4%)
Blood and lymphatic system disorders - Other	5/49 (10.2%)
Leukocytosis	1/49 (2%)
Cardiac disorders
Cardiac disorders - Other	2/49 (4.1%)
Sinus bradycardia	1/49 (2%)
Ear and labyrinth disorders
Hearing impaired	1/49 (2%)
Tinnitus	1/49 (2%)
Endocrine disorders
Adrenal insufficiency	1/49 (2%)
Endocrine disorders - Other	1/49 (2%)
Hypothyroidism	3/49 (6.1%)
Eye disorders
Blurred vision	2/49 (4.1%)
Cataract	1/49 (2%)
Conjunctivitis	1/49 (2%)
Eye disorders - Other	6/49 (12.2%)
Glaucoma	1/49 (2%)
retinal detachment	1/49 (2%)
watering eyes	1/49 (2%)
Gastrointestinal disorders
Abdominal pain	11/49 (22.4%)
Ascites	1/49 (2%)
Bloating	1/49 (2%)
Cheilitis	1/49 (2%)
Constipation	14/49 (28.6%)
Diarrhea	19/49 (38.8%)
Dry mouth	4/49 (8.2%)
Dyspepsia	1/49 (2%)
Dysphagia	1/49 (2%)
Esophagitis	1/49 (2%)
Fecal incontinence	1/49 (2%)
Flatulence	2/49 (4.1%)
Gastrointestinal disorders - Other, specify	12/49 (24.5%)
Mucositis oral	3/49 (6.1%)
Nausea	22/49 (44.9%)
Oral hemorrhage	1/49 (2%)
Oral pain	1/49 (2%)
Rectal hemorrhage	1/49 (2%)
Stomach pain	1/49 (2%)
Vomiting	12/49 (24.5%)
Lower gastrointestinal hemorrhage	1/49 (2%)
Anal hemorrhage	1/49 (2%)
Gastroesophageal reflux disease	2/49 (4.1%)
General disorders
Chills	6/49 (12.2%)
Edema face	2/49 (4.1%)
Fatigue	25/49 (51%)
Fever	4/49 (8.2%)
Flu like symptoms	3/49 (6.1%)
Gait disturbance	2/49 (4.1%)
General disorders and administration site conditions - Other, specify	12/49 (24.5%)
Pain	1/49 (2%)
Edema limbs	15/49 (30.6%)
Infusion related reaction	1/49 (2%)
Localized edema	2/49 (4.1%)
Non-cardiac chest pain	1/49 (2%)
Immune system disorders
Anaphylaxis	1/49 (2%)
Infections and infestations
Infections and infestations - Other, specify	1/49 (2%)
Paronychia	1/49 (2%)
Upper respiratory infection	3/49 (6.1%)
Urinary tract infection	3/49 (6.1%)
Wound infection	1/49 (2%)
Mucosal infection	2/49 (4.1%)
Injury, poisoning and procedural complications
Bruising	1/49 (2%)
Fall	1/49 (2%)
Fracture	1/49 (2%)
Injury, poisoning and procedural complications - Other, specify	2/49 (4.1%)
Postoperative hemorrhage	1/49 (2%)
Investigations
Alanine aminotransferase increased	7/49 (14.3%)
Alkaline phosphatase increased	3/49 (6.1%)
Aspartate aminotransferase increased	12/49 (24.5%)
Blood bilirubin increased	2/49 (4.1%)
Cardiac troponin I increased	1/49 (2%)
Cardiac troponin T increased	1/49 (2%)
CPK increased	10/49 (20.4%)
Creatinine increased	6/49 (12.2%)
INR increased	1/49 (2%)
Investigations - Other, specify	4/49 (8.2%)
Lymphocyte count decreased	1/49 (2%)
Neutrophil count decreased	1/49 (2%)
Platelet count decreased	4/49 (8.2%)
Weight gain	3/49 (6.1%)
Weight loss	3/49 (6.1%)
Hemoglobin increased	1/49 (2%)
Metabolism and nutrition disorders
Anorexia	9/49 (18.4%)
Dehydration	4/49 (8.2%)
Hypercalcemia	1/49 (2%)
Hyperglycemia	2/49 (4.1%)
Hyperkalemia	1/49 (2%)
Hyperuricemia	1/49 (2%)
Hypoalbuminemia	6/49 (12.2%)
Hypoglycemia	2/49 (4.1%)
Hypokalemia	4/49 (8.2%)
Hypomagnesemia	4/49 (8.2%)
Hyponatremia	7/49 (14.3%)
Hypophosphatemia	2/49 (4.1%)
Metabolism and nutrition disorders - Other	2/49 (4.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/49 (6.1%)
Arthritis	1/49 (2%)
Back pain	6/49 (12.2%)
Bone pain	2/49 (4.1%)
Flank pain	1/49 (2%)
Musculoskeletal and connective tissue disorder - Other, specify	9/49 (18.4%)
Myalgia	3/49 (6.1%)
Neck pain	1/49 (2%)
Pain in extremity	2/49 (4.1%)
Generalized muscle weakness	5/49 (10.2%)
Muscle weakness lower limb	2/49 (4.1%)
Muscle weakness trunk	1/49 (2%)
Muscle weakness upper limb	1/49 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other,	1/49 (2%)
Nervous system disorders
Cognitive disturbance	1/49 (2%)
Dizziness	11/49 (22.4%)
Dysgeusia	5/49 (10.2%)
Headache	12/49 (24.5%)
Hypersomnia	1/49 (2%)
Lethargy	1/49 (2%)
Movements involuntary	1/49 (2%)
Nervous system disorders - Other, specify	7/49 (14.3%)
Peripheral motor neuropathy	2/49 (4.1%)
Peripheral sensory neuropathy	3/49 (6.1%)
Syncope	1/49 (2%)
Psychiatric disorders
Anxiety	4/49 (8.2%)
Confusion	1/49 (2%)
Depression	2/49 (4.1%)
Insomnia	7/49 (14.3%)
Renal and urinary disorders
Hematuria	1/49 (2%)
Renal and urinary disorders - Other, specify	4/49 (8.2%)
Urinary frequency	6/49 (12.2%)
Urinary incontinence	1/49 (2%)
Urinary tract pain	1/49 (2%)
Acute kidney injury	1/49 (2%)
Reproductive system and breast disorders
Pelvic pain	1/49 (2%)
Reproductive system and breast disorders - Other	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Cough	9/49 (18.4%)
Dyspnea	12/49 (24.5%)
Hiccups	1/49 (2%)
Hoarseness	2/49 (4.1%)
Hypoxia	1/49 (2%)
Nasal congestion	3/49 (6.1%)
Postnasal drip	2/49 (4.1%)
Productive cough	2/49 (4.1%)
Pulmonary fibrosis	1/49 (2%)
Respiratory, thoracic and mediastinal disorders - Other	5/49 (10.2%)
Sore throat	5/49 (10.2%)
Sinus disorder	1/49 (2%)
Skin and subcutaneous tissue disorders
Alopecia	5/49 (10.2%)
Dry skin	7/49 (14.3%)
Erythroderma	2/49 (4.1%)
Hyperhidrosis	1/49 (2%)
Pruritus	5/49 (10.2%)
Rash acneiform	14/49 (28.6%)
Rash maculo-papular	7/49 (14.3%)
Skin and subcutaneous tissue disorders - Other, specify	16/49 (32.7%)
Urticaria	1/49 (2%)
Vascular disorders
Hot flashes	1/49 (2%)
Hypertension	4/49 (8.2%)
Hypotension	3/49 (6.1%)
Thromboembolic event	2/49 (4.1%)

Limitations/Caveats

Because of the lack of clinical response, it was decided that enrollment should discontinue. Twenty patients who received MEK162 were evaluated for the primary outcome; secondary outcome was not evaluated.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.