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
Overview
- Phase
- Phase 2
- Intervention
- cytology specimen collection procedure
- Conditions
- Recurrent Melanoma
- Sponsor
- Yale University
- Enrollment
- 49
- Locations
- 6
- Primary Endpoint
- Best Overall Response Rate (BORR)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Detailed Description
PRIMARY OBJECTIVES: I. 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: I. 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. II. 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. III. 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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
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.
Intervention: cytology specimen collection procedure
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.
Intervention: MEK 162 therapy or molecularly targeted therapy
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.
Intervention: therapeutic procedure
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.
Intervention: laboratory biomarker analysis
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.
Intervention: quality-of-life assessment
Outcomes
Primary Outcomes
Best Overall Response Rate (BORR)
Time Frame: Up to 1 year
The best overall response rate (BORR) was assessed up to 1 year.
Secondary Outcomes
- Progression-Free Survival (PFS)(From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year)