Temozolomide or Selumetinib in Treating Patients With Metastatic Melanoma of the Eye
NCT ID: NCT01143402
Last Updated: 2017-07-26
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
120 participants
INTERVENTIONAL
2010-06-30
2016-05-31
Brief Summary
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Detailed Description
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I. To assess the progression-free survival (PFS) in three separate patient populations with uveal melanoma: Patients on COHORT 1 (guanine nucleotide binding protein \[G protein\], q polypeptide \[Gnaq\]/G protein, alpha 11 \[Gna11\] mutant uveal melanoma; temozolomide \[TMZ\]/dacarbazine \[DTIC\] naive) treated with AZD6244 (selumetinib) or TMZ (or DTIC); patients on both COHORT 1 and COHORT 2 (Gnaq/Gna11 mutant and Gnaq/Gna11 wild-type uveal melanoma; TMZ/DTIC naive) treated with AZD6244 or TMZ (or DTIC); and patients on COHORT 3 (Gnaq/Gna11 mutant or wild-type uveal melanoma; previously treated with TMZ/DTIC) treated with AZD6244.
SECONDARY OBJECTIVES:
I. Overall survival (OS). II. Overall response rate (RR). III. To determine the tolerability of AZD6244 in patients with advanced uveal melanoma.
IV. To correlate PFS, OS, and overall RR with Gnaq and Gna11 mutational status.
TERTIARY OBJECTIVES:
I. To correlate clinical outcome with baseline phosphorylated (p)-extracellular signal-regulated kinases (ERK), p-v-akt murine thymoma viral oncogene homolog 1 (AKT), and phosphatase and tensin homolog (PTEN) expression by immunohistochemistry.
II. To correlate clinical outcome with changes in p-ERK, p-AKT, and PTEN expression by immunohistochemistry.
III. To correlate clinical outcome with changes in Ki67 and cleaved caspase 3. IV. To explore the overall quality of life (QoL) of the treatment groups as measured by the Functional Assessment of Cancer Therapy-Melanoma (FACT-M) questionnaire.
V. To explore the radiographic effects of treatment with AZD6244 as assessed by 18F fluorothymidine (FLT)-positron emission tomography (PET) imaging.
OUTLINE: Patients in groups 1 and 2 are randomized to 1 of 2 treatment arms. Patients in group 3 are assigned to arm II.
ARM I: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who are unable to be treated with temozolomide may be treated with dacarbazine intravenously (IV) every 3 weeks (with approval from the Principal Investigator). Patients who experience disease progression may crossover to arm II.
ARM II: Patients receive selumetinib PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm I (temozolomide)
Patients receive temozolomide PO QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who are unable to be treated with temozolomide may be treated with dacarbazine IV every 3 weeks (with approval from the Principal Investigator). Patients who experience disease progression may crossover to arm II.
Dacarbazine
Given IV
Laboratory Biomarker Analysis
Correlative studies
Quality-of-Life Assessment
Ancillary studies
Temozolomide
Given PO
Arm II (selumetinib)
Patients receive selumetinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis
Correlative studies
Quality-of-Life Assessment
Ancillary studies
Selumetinib
Given PO
Interventions
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Dacarbazine
Given IV
Laboratory Biomarker Analysis
Correlative studies
Quality-of-Life Assessment
Ancillary studies
Selumetinib
Given PO
Temozolomide
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
* Life expectancy of greater than 3 months
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Leukocytes \>= 3,000/mcL
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \>= 9.0 g/dL (not requiring transfusions within the past 2 weeks)
* Total bilirubin =\< 1.5 times upper limit of normal; note: patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 times upper limit of normal for patients with no concurrent liver metastases
* AST(SGOT)/ALT(SGPT) =\< 5 X institutional ULN for patients with concurrent liver metastases
* Creatinine =\< 1.5 mg/dL
* Tumor Gnaq and Gna11 status must be determined on all patients using a Clinical Laboratory Improvement Act (CLIA) approved assay; if initial CLIA testing is performed locally, patients must consent to provide a tumor block or unstained slides to MSKCC for central review of Gnaq and Gna11 status; this central review may be performed retrospectively and will not delay patient treatment on study
* Patients must agree to provide all imaging studies for central radiology review; this central radiology review may be performed retrospectively and will not be utilized for decision making for patients on study
* Ability to understand and the willingness to sign a written informed consent document
* Eligibility for enrollment in each cohort is dependent upon tumor Gnaq/Gna11 status and prior therapy as follows:
* Cohort 1: no prior TMZ or DTIC; mutant Gnaq/Gna11 status
* Cohort 2: no prior TMZ or DTIC; wild-type Gnaq/Gna11 status
* Cohort 3: received prior TMZ or DTIC; mutant or wild-type Gnaq/Gna11 status
* Every effort must be made to avoid administration of drugs that are inhibitors or inducers of cytochrome P450 1A2 (CYP1A2) and CYP3A4
Exclusion Criteria
* Patients may not be receiving any other investigational agents
* Patients with active or untreated brain metastases; treated brain metastases must have been stable for at least 2 months
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TMZ or DTIC or AZD6244
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or bleeding, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study; breast-feeding should be discontinued if the mother is treated with AZD6244
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; women of child-bearing potential must have a negative pregnancy test prior to entry; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; please note that the AZD6244 manufacturer recommends that adequate contraception for male patients should be used for 16 weeks post-last dose due to sperm life cycle
* Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; patients with compensated HIV, with adequate cluster of differentiation (CD)4+ T-cell counts, and not requiring antiretroviral medication will be allowed
* Patients taking vitamin E supplements while on study
* No concomitant anti-cancer chemotherapy or other systemic drugs; palliative radiation therapy will be allowed as long as the patient meets all other eligibility criteria
* Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
* Patients with corrected QT (QTc) interval \> 450 msecs or other factors that increase the risk of QTc prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions are excluded
* Every effort must be made to avoid the use of a concomitant medication that can prolong the QTc interval while receiving AZD6244; if the patient cannot discontinue medications that prolong the QTc interval while receiving AZD6244, close cardiac monitoring should be performed
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Paul Chapman
Role: PRINCIPAL_INVESTIGATOR
Memorial Sloan Kettering Cancer Center
Locations
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University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States
Mount Sinai Medical Center
Miami Beach, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Fairview Ridges Hospital
Burnsville, Minnesota, United States
Mercy Hospital
Coon Rapids, Minnesota, United States
Fairview-Southdale Hospital
Edina, Minnesota, United States
Unity Hospital
Fridley, Minnesota, United States
Hutchinson Area Health Care
Hutchinson, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
Maplewood, Minnesota, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, United States
Hennepin County Medical Center
Minneapolis, Minnesota, United States
North Memorial Medical Health Center
Robbinsdale, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States
Regions Hospital
Saint Paul, Minnesota, United States
United Hospital
Saint Paul, Minnesota, United States
Saint Francis Regional Medical Center
Shakopee, Minnesota, United States
Ridgeview Medical Center
Waconia, Minnesota, United States
Minnesota Oncology and Hematology PA-Woodbury
Woodbury, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Wisconsin Clinical Cancer Center
Milwaukee, Wisconsin, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
Countries
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References
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Atkinson TM, Hay JL, Shoushtari A, Li Y, Paucar DJ, Smith SC, Kudchadkar RR, Doyle A, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Marr B, Abramson DH, Dickson MA, Schwartz GK, Carvajal RD. Relationship between physician-adjudicated adverse events and patient-reported health-related quality of life in a phase II clinical trial (NCT01143402) of patients with metastatic uveal melanoma. J Cancer Res Clin Oncol. 2017 Mar;143(3):439-445. doi: 10.1007/s00432-016-2318-x. Epub 2016 Dec 5.
Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014 Jun 18;311(23):2397-405. doi: 10.1001/jama.2014.6096.
Chen X, Schwartz GK, DeAngelis LM, Kaley T, Carvajal RD. Dropped head syndrome: report of three cases during treatment with a MEK inhibitor. Neurology. 2012 Oct 30;79(18):1929-31. doi: 10.1212/WNL.0b013e318271f87e. Epub 2012 Oct 17. No abstract available.
Other Identifiers
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NCI-2011-01411
Identifier Type: REGISTRY
Identifier Source: secondary_id
CDR0000674866
Identifier Type: -
Identifier Source: secondary_id
10-053
Identifier Type: OTHER
Identifier Source: secondary_id
8443
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2011-01411
Identifier Type: -
Identifier Source: org_study_id
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