- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04427306
Neoadjuvant T-VEC in High Risk Early Melanoma
Biomarker Analysis of Neoadjuvant Intralesional Therapy in High Risk Early Melanoma
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.
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Shari Nichols, CCRP
- Phone Number: (916)551-3242
- Email: slnichols@ucdavis.edu
Study Locations
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California
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Sacramento, California, United States, 95817
- UC Davis Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
- 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.
- Willingness to undergo mandatory pre-treatment biopsy (unless there is adequate archival tumor specimen available) and mandatory on-treatment biopsy.
- Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Or, female subjects of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first study drug administration.
- Male and female subjects who agree to use highly effective method of birth control (e.g., implants, injectables, birth control pills with two hormones, intrauterine devices [IUDs], complete abstinence or sterilized partner, and female sterilization) and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug.
- Biopsy-proven resectable primary cutaneous melanoma > 2.0mm in depth with residual tumor or local, in-transit, or dermal oligometastatic resectable recurrence in a treatment- naïve patient not otherwise eligible for systemic therapy
- Residual pigmented cutaneous lesion accessible to intralesional injection
Exclusion Criteria
- 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).
- Current enrollment in another clinical trial
- Patients who are know to be sensitive to any of the products or components of T-VEC
- Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use.
- Previous treatment with talimogene laherparepvec or any other oncolytic virus.
- Prior therapy with tumor vaccine or received live vaccine within 28 days prior to enrollment.
- Adjuvant hormonal therapy is allowed if appropriate for planned study.
- Prior radiotherapy in which the field does not overlap the injection sites or non- immunosuppressive targeted therapy within 14 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 14 days prior to enrollment
History of other malignancy within the past 5 years with the following exceptions:
- Adequately treated non melanoma skin cancer without evidence of disease at the time of enrollment
- Adequately treated cervical carcinoma in situ without evidence of disease at the time of enrollment
- Adequately treated breast ductal carcinoma in situ without evidence of disease at the time of enrollment
- Prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of enrollment.
- Subjects who are unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for HSV-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or infants under the age of 3 months, during talimogene laherparepvec treatment and through 30 days after the last dose
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Treatment (talimogene laherparepvec)
This study all subject get the research treatment drug (talimogene laherparepvec)
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(talimogene laherparepvec) will be given prior to surgery.
Standard care the patients receive the drug after sugery
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic response
Time Frame: At surgery
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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:
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
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael C Lowe, MD, Emory University Winship Cancer Institute
- Principal Investigator: Cameron Gaskill, MD, UC Davis Department of Surgery
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1529612
- UCDCCSO034 (Other Identifier: UC Davis Cancer Center)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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