Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma
Conditions
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.
Interventions
OTHERcytology specimen collection procedure
Undergo collection of tissue and blood samples
DRUGMEK 162 therapy or molecularly targeted therapy
molecularly targeted therapy, MEK 162 therapy
PROCEDUREtherapeutic procedure
OTHERlaboratory biomarker analysis
Correlative studies
OTHERquality-of-life assessment
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate (BORR) | Up to 1 year | The best overall response rate (BORR) was assessed up to 1 year. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | Arm I (Molecularly Targeted Therapy) |
|---|---|
| Age, Customized 30-39 | 1 Participants |
| Age, Customized 40-49 | 6 Participants |
| Age, Customized 50-59 | 10 Participants |
| Age, Customized 60-69 | 13 Participants |
| Age, Customized 70-79 | 15 Participants |
| Age, Customized 80-89 | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants |
| Race/Ethnicity, Customized Asian or Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Black, not of Hispanic Origin | 2 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants |
| Race/Ethnicity, Customized Other/ | 4 Participants |
| Race/Ethnicity, Customized White, not of Hispanic Origin | 43 Participants |
| Region of Enrollment United States | 49 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 49 |
| other Total, other adverse events | 32 / 49 |
| serious Total, serious adverse events | 48 / 49 |
Outcome results
Primary
Best Overall Response Rate (BORR)
The best overall response rate (BORR) was assessed up to 1 year.
Time frame: Up to 1 year
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Molecularly Targeted Therapy) | Best Overall Response Rate (BORR) | Progressive Disease | 2 Participants |
| Arm I (Molecularly Targeted Therapy) | Best Overall Response Rate (BORR) | Stable Disease | 17 Participants |
| Arm I (Molecularly Targeted Therapy) | Best Overall Response Rate (BORR) | Partial Response | 1 Participants |
Secondary
Progression-Free Survival (PFS)
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
Population: 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.