Intermittent Selumetinib for Uveal Melanoma
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|ClinicalTrials.gov Identifier: NCT02768766|
Recruitment Status : Recruiting
First Posted : May 11, 2016
Last Update Posted : December 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Uveal Melanoma||Drug: Selumetinib||Phase 1|
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and arises from melanocytes within the choroid plexus of the eye. The development of metastasis is common and occurs in approximately 50% of patients with posterior UM within 15 years of initial diagnosis and treatment. As no effective systemic therapy has yet been identified for this disease, outcomes for metastatic UM are poor with a median survival of 12 months.
There is no FDA approved therapy for patients with advanced UM. Studies have shown that inhibition of the Mitogen-activated protein kinase (MAPK) pathway with the MEK inhibitor selumetinib (hyd-sulfate AZD6244) is an effective therapy for uveal melanoma but despite this treatment, cures are not achieved. Although drugs such as selumetinib have been studied when patients take the treatment every day, research has shown that in some cases, it may be better to use the treatment on an intermittent schedule. Such a strategy may reduce the side effects, allow higher doses of the drug to be used, more completely block the MAPK pathway, and prevent the development of drug resistance mechanisms within the tumor.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multi-Center Phase Ib Study of Intermittent Dosing of the MEK Inhibitor, Selumetinib, in Patients With Advanced Uveal Melanoma Not Previously Treated With a MEK Inhibitor|
|Actual Study Start Date :||February 28, 2017|
|Estimated Primary Completion Date :||September 2022|
|Estimated Study Completion Date :||September 2022|
Subjects will receive selumetinib (hyd-sulfate AZD6244) orally twice a day for three days followed by four days off in four week cycles starting at a dose of 125mg. The doses to be studied on a 3 day on, 4 day off schedule are 100mg, 125mg, 150mg, 175mg, 200mg and 225mg as per the time to event continual reassessment (TITE-CRM) design.
100mg, 125mg, 150mg, 175mg, 200mg or 225mg of oral capsules
An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK) or MAPK/extracellular-signal-regulated kinase (ERK) kinase) 1 and 2. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.
Other Name: hyd-sulfate AZD6244
- Maximum Tolerated Dose (MTD) of intermittent selumetinib [ Time Frame: Up to 2 years ]MTD is defined as the dose associated with a target probability of dose limiting toxicity (DLT) of 25%. DLT will be assessed over the course of first two cycles of treatment (i.e., 8 weeks) for dose selection for subsequent patient treatment initiation.
- Number of adverse events (AEs) [ Time Frame: Up to 2 years ]Number of AE throughout the study to assess the safety and tolerability of intermittent selumetinib
- Number of serious adverse events (SAEs) [ Time Frame: Up to 2 years ]Number of SAE throughout the study to assess the safety and tolerability of intermittent selumetinib
- Number of subjects with Dose Limiting Toxicity (DLT) [ Time Frame: Up to 2 years ]Number of subjects with DLT throughout the study to assess the safety and tolerability of intermittent selumetinib
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02768766
|Contact: Lisa Olmos, RNfirstname.lastname@example.org|
|Contact: Richard Carvajal, MDemail@example.com|
|United States, New York|
|Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Richard Carvajal, MD firstname.lastname@example.org|
|Principal Investigator: Richard Carvajal, MD|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Alexander N Shoushtari, M.D 646-888-4161 email@example.com|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Sapna Patel, M.D 713-792-2921 firstname.lastname@example.org|
|Principal Investigator:||Richard Carvajal, MD||Columbia University|