Neoadjuvant T-VEC in High Risk Early Melanoma

NCT04427306 | Suspended Phase 2 FDA Drug

• 2 other identifiers: 1529612UCDCCSO034
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Pathologic response

  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.

  At surgery

Study Arms (1)

Treatment (talimogene laherparepvec)

EXPERIMENTAL

This study all subject get the research treatment drug (talimogene laherparepvec)

Drug: T-Vec

Interventions

T-Vec DRUG

(talimogene laherparepvec) will be given prior to surgery. Standard care the patients receive the drug after sugery

Also known as: talimogene laherparepvec, Amgen

Treatment (talimogene laherparepvec)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and willingness to sign an informed consent form.
• Ability to adhere to the study visit schedule and other protocol requirements.
• Men and women ≥18 years of age.
• ECOG performance status score of 0-1 (Appendix 13.1) / Karnofsky Performance Status (KPS) performance status of 60% or greater.
• Life expectancy ≥ 3 months.
• Hematology parameters defined by:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L,
• Platelet count ≥ 75 × 109/L, and
• Hemoglobin ≥ 8 g/dL (may have been transfused)
• Blood chemistry levels defined by:
• Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range
• AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
• INR and aPTT ≤1.5 x ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to first treatment)
• Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula.
• Subjects with active hepatitis B virus (Hep B) and with untreated hepatitis C virus (HCV) are allowed.

You may not qualify if:

• Pregnant or lactating women.
• Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Any significant medical condition including additional malignancies, laboratory abnormalities, or psychiatric illness that would prevent the subject from participating and adhering to study related procedures.
• Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial.
• Severe infection that in the opinion of the investigator would interfere with patient safety or compliance on trial within 4 weeks prior to enrollment.
• Melanoma \>/= 2.0mm in depth without residual disease following biopsy
• Previous exposure to talimogene laherparepvec or systemic therapies
• Concurrent cancer or treatment for a concurrent cancer, except treated non-melanoma skin cancer
• Regional or systemic metastases
• History of evidence of symptomatic autoimmune disease requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Immunosuppressed state, including the following:
• Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease, concurrent opportunistic infection, receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 7 days prior to enrollment.
• Prior immunosuppressive, chemotherapy, radiotherapy (in which the field encompassed a planned injection site), biological cancer therapy, or major surgery within 28 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment.
• Active human immunodeficiency virus (HIV) infection
• Active herpetic skin lesions or prior complication of herpes simplex virus-1 infection (e.g., herpetic keratitis or encephalitis).

Sponsors & Collaborators

• University of California, Davis: lead
• Amgen: collaborator

Study Sites (1)

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Related Links

• Learn more or sign up for the study here!

MeSH Terms

Conditions

Melanoma

Interventions

talimogene laherparepvec; romiplostim

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Cameron Gaskill, MD

  UC Davis Department of Surgery

  PRINCIPAL INVESTIGATOR

• Michael C Lowe, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: June 11, 2020
• Study Start: May 21, 2020
• Primary Completion: June 27, 2022
• Study Completion: May 21, 2024
• Last Updated: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)