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Iris MelanomaPhase 2NCT01143402

Temozolomide or Selumetinib in Treating Patients With Metastatic Melanoma of the Eye

A Phase 2 study testing Dacarbazine, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Iris Melanoma and Medium/Large Size Posterior Uveal Melanoma, run by National Cancer Institute (NCI) at 33 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dacarbazine, Laboratory Biomarker Analysis and Quality-of-Life Assessment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
33 sitesin 2 countries
Study dates
Jun 2010to May 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 20Show fewer
  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

33 sites in 2 countries.

33 sites in 2 countries

United States32 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Fairview-Southdale Hospital

    Edina, Minnesota, 55435

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Hutchinson Area Health Care

    Hutchinson, Minnesota, 55350

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Wisconsin Clinical Cancer Center

    Milwaukee, Wisconsin, 53226

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Saint Francis Regional Medical Center

    Shakopee, Minnesota, 55379

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Ridgeview Medical Center

    Waconia, Minnesota, 55387

  • Minnesota Oncology and Hematology PA-Woodbury

    Woodbury, Minnesota, 55125

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: Randomized Phase II Trial of Temozolomide Versus Hyd-Sulfate AZD6244 [NSC 748727] in Patients With Metastatic Uveal Melanoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Being tested
Dacarbazine, Laboratory Biomarker Analysis, Quality-of-Life Assessment, Selumetinib, Temozolomide
Medical subject headings
Uveal Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DacarbazineDrug

    Also called 4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • SelumetinibDrug

    Also called ARRY-142886, AZD6244, MEK Inhibitor AZD6244

    Given PO

  • TemozolomideDrug

    Also called CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831

    Given PO

Study groups in NCT01143402
Study groupRoleWhat they receive
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.
Receives: Drug: Dacarbazine; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Temozolomide
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.
Receives: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Selumetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Median Overall Survival (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.

    Measured: The time from randomization to death due to any cause, assessed up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionMay 2016
  4. Study completionMay 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01143402
Sponsor's protocol ID
NCI-2011-01411
Other IDs
NCI-2011-01411, CDR0000674866, 10-053, 8443, N01CM00070, N01CM00071, N01CM00099, N01CM00100
Status last verified
Jun 2017
First submitted
11 Jun 2010
Last updated
26 Jul 2017
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 27921276

  • 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.

    PubMed 24938562

  • 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.

    PubMed 23077008

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dacarbazine, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Iris Melanoma and Medium/Large Size Posterior Uveal Melanoma, run by National Cancer Institute (NCI) at 33 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (Evaluable Randomized Patients) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01143402, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2017.

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