Clinical Review

An Analysis of the Clinical Trial Landscape for Cutaneous Melanoma

Cutis. 2015 September;96(3):186-190

Recognizing current trends and obstacles in melanoma clinical trial development is critical to future progress in this field. This article examines the melanoma research enterprise to identify changing trends and potential barriers to success. All trials registered at ClinicalTrials.gov after September 2005 were evaluated for possible inclusion. A total of 777 interventional trials designed specifically for cutaneous melanoma patients were included. Geographic trial distribution as well as disease state and type of intervention were analyzed and compared among each group. ClinicalTrials.gov is an invaluable tool to study the research enterprise. Further studies are needed on prevention and early detection of melanoma in the curative setting, a critical role for dermatologists.

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Practice Points

The landscape of melanoma clinical trial research has shifted to follow advances in targeted therapy  and immunotherapy.
With these new treatments there is an increased risk for nonmelanoma skin toxicities requiring increased vigilance and collaboration between dermatologists and oncologists.
Physicians are encouraged to use ClinicalTrials.gov to find details and contact information for actively recruiting clinical trials and results on completed trials.

References

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The incidence of cutaneous melanoma, the deadliest form of skin cancer, has been steadily increasing over the last several decades.¹ Currently, there are 73,870 new diagnoses of melanoma anticipated in the United States in 2015 alone.² Many cases of melanoma are caught at early, actionable, and curable stages thanks in part to patient education and screening by dermatologists.3 However, until recently, few options existed for the treatment of locally advanced and metastatic melanomas, with a median survival rate of less than 1 year.⁴

Clinical trials represent the most reliable method for advancing treatment and improving outcomes for patients with disease; however, patient accrual and access to clinical trials remain formidable barriers. Studies have suggested that patients in rural areas perceive both an increased distance to clinical trial sites and a lack of awareness of available trials compared to their urban counterparts. Additionally, studies have shown that provider awareness of actively enrolling clinical trials in their respective fields is a key determinate in patient enrollment.⁵ Finally, insufficient funding and lack of collaboration has resulted in many small phase 1 or phase 2 single-center trials, which are less likely to quickly impact clinical care.⁶ Increased awareness of the ClinicalTrials.gov registry, a publicly available and easily accessible database, can facilitate referral, enrollment, and collaboration among physicians, patients, and researchers alike.

Using the ClinicalTrials.gov database, we sought to analyze the clinical trial landscape for cutaneous melanoma to understand the current state of melanoma research, future direction, and potential barriers that may impede success.

Methods

The primary objective was to provide a snapshot of the melanoma clinical research landscape from 2005 to 2013, including the number of registered trials, phase distribution, recruitment status, location of trials, type of intervention, and disease state being studied. Secondary objectives included describing patterns of clinical trial distribution within the United States in the context of melanoma mortality and examining changing trends in interventions studied in trials over time.

ClinicalTrials.gov is a comprehensive online registry of clinical trials conducted in the United States and abroad that is maintained by the National Library of Medicine.⁷ Although the initiative was launched in 2000, the registry became effectively comprehensive in September 2005 when the International Committee of Medical Journal Editors declared prospective registration of clinical trials as a prerequisite for publication. The US Food and Drug Administration followed suit in September 2007, expanding the requirements for registration and declaring penalties for parties who did not comply.⁸ Each registered trial can be found through searchable keywords, and each study page contains details of study design, principal investigators, and inclusion and exclusion criteria, as well as contact information for enrollment.

Study Selection

Clinical trials registered between September 15, 2005, and December 31, 2013, were evaluated; a total of 138,312 trials were found to be registered on ClinicalTrials.gov during that time period. We limited our study selection to interventional studies, which were filtered by topic to yield only those pertaining to melanoma patients. To minimize reporting bias, trials registered prior to the implementation of the International Committee of Medical Journal Editors’ reporting requirements were excluded. To focus specifically on the landscape of trials in cutaneous melanoma, trials investigating multiple advanced malignancies, uveal or ocular melanoma, and mucosal melanoma were manually excluded.

Study Variables

Information on each clinical trial was extracted from ClinicalTrials.gov. Each trial was manually reviewed by an investigator to determine the disease state and type of intervention being studied. Studies investigating multiple modalities concurrently were classified as “other.”

Data Analysis

Study variables were first analyzed among the entire cohort as a whole. Using each trial location and a python script based on open-source code, the number of actively recruiting melanoma trials in each US county was identified and mapped. County-level, melanoma-specific mortality data from 2001 to 2010 was extracted from the Centers for Disease Control and Prevention’s WONDER (Wide-ranging Online Data for Epidemiologic Research) mortality database (wonder.cdc.gov). Finally, to analyze changing trends in cutaneous melanoma investigation, trials were grouped into 3 categories based on the date they were received on ClinicalTrials.gov: (1) 2005-2007,  (2) 2008-2010, and (3) 2011-2013. Disease state and type of intervention were analyzed and compared among each group using the χ² statistic.

Results

Of the 138,312 trials registered on ClinicalTrials.gov between September 15, 2005, and December 31, 2013, only 931 were identified as interventional studies pertaining to melanoma patients. Of these, 154 were excluded because of a focus on uveal, ocular, or mucosal melanoma or because of the inclusion of participants with multiple types of advanced malignancies. The final analysis included 777 trials specifically focusing on cutaneous melanoma.