Temozolomide or Selumetinib in Treating Patients With Metastatic Melanoma of the Eye
Randomized Phase II Trial of Temozolomide Versus Hyd-Sulfate AZD6244 [NSC 748727] in Patients With Metastatic Uveal Melanoma
12 other identifiers
interventional
120
2 countries
33
Brief Summary
This randomized phase II trial studies temozolomide to see how well it works compared to selumetinib in treating patients with melanoma of the eye that has spread to other places in the body. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether temozolomide is more effective than selumetinib in treating melanoma of the eye.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jun 2010
Longer than P75 for phase_2
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2010
CompletedFirst Submitted
Initial submission to the registry
June 11, 2010
CompletedFirst Posted
Study publicly available on registry
June 14, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2016
CompletedResults Posted
Study results publicly available
May 18, 2017
CompletedJuly 26, 2017
June 1, 2017
5.9 years
June 11, 2010
April 7, 2017
June 26, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) (Evaluable Randomized Patients)
The primary analysis will be performed among the Gnaq/Gna11 mutant patients. A stratified logrank test will be performed stratified by mutation status, M stage, and number of prior systemic therapies for metastatic disease. Due to the potential for a large number of strata and small strata sizes, the standard asymptotic stratified logrank test will be verified for robustness utilizing a permutation reference distribution.
The time from randomization to the earlier date of objective disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria or death due to any cause in the absence of progression, assessed up to 5 years
Secondary Outcomes (1)
Median Overall Survival (Evaluable Randomized Patients)
The time from randomization to death due to any cause, assessed up to 5 years
Other Outcomes (12)
Objective Disease Progression
assessed up to 5 years
Overall Survival
The time from randomization to death due to any cause, assessed up to 5 years
Response Rate (Complete and Partial Response)
Up to 5 years
- +9 more other outcomes
Study Arms (2)
Arm I (temozolomide)
EXPERIMENTALPatients 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.
Arm II (selumetinib)
EXPERIMENTALPatients receive selumetinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Ancillary studies
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have metastatic histologically or cytologically confirmed uveal melanoma; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of diagnosis will be performed at Memorial Sloan-Kettering Cancer Center (MSKCC) or at a participating site
- 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
- +5 more criteria
You may not qualify if:
- Patients may have had any number of prior therapies, but cannot have previously been treated with a mitogen-activated protein kinase kinase (MEK) inhibitor; at least 3 weeks must have elapsed since the last dose of systemic therapy; at least 6 weeks must have elapsed if the last regimen included carmustine (BCNU), mitomycin C or an anti-CTLA4 antibody; patients must have experienced disease progression on their prior therapy in the opinion of the treating investigator
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
Mount Sinai Medical Center
Miami Beach, Florida, 33140, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Fairview Ridges Hospital
Burnsville, Minnesota, 55337, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Fairview-Southdale Hospital
Edina, Minnesota, 55435, United States
Unity Hospital
Fridley, Minnesota, 55432, United States
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109, United States
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Minnesota Oncology and Hematology PA-Woodbury
Woodbury, Minnesota, 55125, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Wisconsin Clinical Cancer Center
Milwaukee, Wisconsin, 53226, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Related Publications (3)
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.
PMID: 27921276DERIVEDCarvajal 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.
PMID: 24938562DERIVEDChen 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.
PMID: 23077008DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Limitations of this study include the unblinded trial design and the lack of central review of imaging studies. Additionally, this trial was designed before activating mutations in exon 4 of GNAQ and GNA11 were reported.
Results Point of Contact
- Title
- Dr. Paul Chapman
- Organization
- Memorial Sloan Kettering Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Paul Chapman
Memorial Sloan Kettering Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 11, 2010
First Posted
June 14, 2010
Study Start
June 1, 2010
Primary Completion
May 1, 2016
Study Completion
May 1, 2016
Last Updated
July 26, 2017
Results First Posted
May 18, 2017
Record last verified: 2017-06