Trials / Completed
CompletedNCT01143402
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
- Status
- Completed
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 120 (actual)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
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.
Detailed description
PRIMARY OBJECTIVES: 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
- Iris Melanoma
- Medium/Large Size Posterior Uveal Melanoma
- Ocular Melanoma With Extraocular Extension
- Recurrent Uveal Melanoma
- Small Size Posterior Uveal Melanoma
- Stage IV Uveal Melanoma
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Dacarbazine | Given IV |
| OTHER | Laboratory Biomarker Analysis | Correlative studies |
| OTHER | Quality-of-Life Assessment | Ancillary studies |
| DRUG | Selumetinib | Given PO |
| DRUG | Temozolomide | Given PO |
Timeline
- Start date
- 2010-06-01
- Primary completion
- 2016-05-01
- Completion
- 2016-05-01
- First posted
- 2010-06-14
- Last updated
- 2017-07-26
- Results posted
- 2017-05-18
Locations
33 sites across 2 countries: United States, Canada
Source: ClinicalTrials.gov record NCT01143402. Inclusion in this directory is not an endorsement.