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

NCT02094872 | Completed Phase 2 Results DMC

• 8 other identifiers: 1408014446NCI-2014-00670WIRB Pro #20140190WO #1-822810-1Invest #161467Study #11445612013-184P30CA022453
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 8

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.

Conditions

Recurrent Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (BORR)

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

  Up to 1 year

Secondary Outcomes (1)

• Progression-Free Survival (PFS)

  From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year

Study Arms (1)

Arm I (molecularly targeted therapy)

EXPERIMENTAL

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; Drug: MEK 162 therapy or molecularly targeted therapy; Procedure: therapeutic procedure; Other: laboratory biomarker analysis; Other: quality-of-life assessment

Interventions

cytology specimen collection procedure OTHER

Undergo collection of tissue and blood samples

Also known as: cytologic sampling

Arm I (molecularly targeted therapy)

MEK 162 therapy or molecularly targeted therapy DRUG

molecularly targeted therapy, MEK 162 therapy

Arm I (molecularly targeted therapy)

therapeutic procedure PROCEDURE

Also known as: Therapeutic Interventions, Therapeutic Method, Therapeutic Technique, Therapy, TX

Arm I (molecularly targeted therapy)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (molecularly targeted therapy)

quality-of-life assessment OTHER

Ancillary studies

Also known as: quality of life assessment

Arm I (molecularly targeted therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

Mayo Clinic Cancer Center

Scottsdale, Arizona, 85259-5499, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06520-8028, United States

Location

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0944, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37240, United States

Location

Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Molecular Targeted Therapy; Coal Tar; Therapeutics

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Tars; Complex Mixtures

Limitations and 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.

Results Point of Contact

• Title: Manuel Avedissian, M.D.
• Organization: Yale University

manuel.avedissian@yale.edu

203-737-3669

Study Officials

• Patricia LoRusso, D.O.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2014
• First Posted: March 24, 2014
• Study Start: May 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: January 2, 2020
• Results First Posted: January 2, 2020

Record last verified: 2019-12

Locations

US (8)