Neoadjuvant T-VEC in High Risk Early Melanoma
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|ClinicalTrials.gov Identifier: NCT04427306|
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : June 11, 2020
Despite the recent notable advances in the treatment of advanced melanoma with application of growing immunotherapies, patterns of response and factors resulting in treatment failure are poorly understood. Moreover, the application of these therapeutics has been limited in the neoadjuvant setting, particularly in earlier stage disease, even though this strategy has improved tolerance and efficacy with other modalities of therapy in other cancer types.
Survival remains significantly poorer for thicker and ulcerated lesions with T3b and T4 lesions demonstrating less than 50% survival at 5 years independent of other prognostic indicators. Oncolytic viral therapies (OVT) stimulate or suppress the immune system in different ways to stop cancer cells from growing and intra-lesional OVT has demonstrated comparable efficacy and durability with greater tolerability than most effective systemic therapy. Talimogene laherparepvec (T-VEC) is the only phase III approved intra-lesional therapy in melanoma and has demonstrated significantly improved overall response rate (64%) and bystander effect (34% in uninjected lesions) in the therapeutic setting for advanced disease.
The investigators propose an open-label, Phase 2 study of talimogene laherparepvec (T-VEC), in the neoadjuvant setting for patients with high-risk, resectable primary and cutaneous melanoma prior to definitive excision. The central hypothesis of this proposal is that neoadjuvant intra-lesional therapy with T-VEC in high risk early stage melanoma will effectively treat local and subclinical distant disease by enhanced immune recognition, immunomodulation of the nodal basin, and still allow for standard of care surgery. The primary aim of this study will be to evaluate for histologic response of melanoma with secondary aim to determine changes in immune response and draining sentinel nodes as well as relationship of immune phenotype to response rate, stage and nodal burden. The investigators plan for thorough exploratory analysis of genetic and microenvironmental changes to identify actionable targets in incomplete as well as evaluation of changes in sentinel burden and subsequent rates of locoregional disease control, recurrence-free survival and overall survival in long term follow up. The investigators predict that histologic clearance of the primary tumor in the surgical specimen will be associated with improved RFS.
In summary, the goal of this project is to conduct a phase II study to evaluate efficacy of Talimogene laherparepvec in the neoadjuvant setting for primary invasive melanoma in effort to improve currently poor outcomes for these tumors. This strategy has not yet been explored in early phase disease despite dramatic results seen with neoadjuvant therapeutics in other cancer types and recent clinical studies demonstrating efficacy of this approach in advanced resectable melanoma. Our ability to predict non-responder from responder to immunotherapeutic agents such as T-VEC is not yet defined and the risk of universal exposure to these systemic agents may outweigh the hypothesized benefit given the potential for immune-mediated toxicity as well as associated costs. More importantly, mechanistic dissection of pathways and molecular/immunological signatures of response and resistance offer the promise of a more rational and targeted selection of immunotherapy to maximize benefits and minimize risks. This study would be first in kind to target high earlier stage melanoma in the neoadjuvant setting with a less toxic intra-tumoral immunotherapy with key correlative endpoints regarding immune mechanisms of response.
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Drug: T-Vec||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||62 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Biomarker Analysis of Neoadjuvant Intralesional Therapy in High Risk Early Melanoma|
|Actual Study Start Date :||May 21, 2020|
|Estimated Primary Completion Date :||May 21, 2022|
|Estimated Study Completion Date :||May 21, 2024|
|Experimental: Treatment (talimogene laherparepvec)||
T-Vec will be given prior to surgery
- Pathologic response [ Time Frame: At surgery ]
Clinical efficacy and biologic effect will be calculated by measuring rates of pathologic response based on assessment of immunologic response and molecular changes in residual tumors. Based on this assessment, patients will be assigned to one of the four categories described below:
Pathologic response defined as:
- Pathologic Complete Response (pCR, defined as 0% residual tumor)
- Major Pathologic Response (defined as ≤10% residual tumor)
- Partial Pathologic Response (pPR, defined as less than or equal to 50% viable tumor cells)
- Pathologic Non-Response (pNR, defined as greater than 50% viable tumor cells)
The analysis will be based on intent-to-treat (ITT). If a patient fails to complete treatment or disease reassessment, then he/she will be counted as a non-responder, even though the exact response is unknown.
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): NCT04427306
|Contact: Hoa Ly, CCRP||(916)firstname.lastname@example.org|
|Contact: Laura Jones, CCRP||(916)email@example.com|
|United States, California|
|UC Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Hoa Ly, CCRP 916-734-4771 firstname.lastname@example.org|
|Contact: Laura Jones, CCRP (916)734-4156 email@example.com|
|Principal Investigator: Amanda Kirane, MD|
|Principal Investigator:||Amanda Kirane, MD||UC Davis Department of Surgery|