Talimogene laherparepvec before Surgery for the Treatment of High-Risk and Treatment-Naive Recurrent Melanoma
18 Years and older, Male and Female
CCSO034 (primary)
NCI-2020-04098
Summary
The phase II trial investigates a viral therapy called talimogene laherparepvec to see how well it works as a first step to shrink a tumor before the main treatment (surgical removal of the tumor) in patients with melanoma that has come back after a period of treatment (recurrent). Talimogene laherparepvec is a modified herpes virus designed to enhance the immune system to destroy melanoma cells. The information learned from this study may help researchers to improve currently poor outcomes associated with early intervention for melanoma care.
Objectives
PRIMARY OBJECTIVE:
I. Evaluate pathologic response of melanoma following intralesional talimogene laherparepvec (T-VEC) in the neoadjuvant setting prior to resection of a primary cutaneous melanoma and sentinel lymph node biopsy or in treatment naive local, in-transit, or dermal oligometastatic recurrence.
SECONDARY OBJECTIVES:
I. Determine the changes in the immune infiltrate in the primary tumor and in the draining sentinel lymph node.
II. Correlate immune phenotype with response rate, disease stage, sentinel node positivity.
III. Evaluate overall and recurrence-free survival.
CORRELATIVE AND EXPLORATORY OBJECTIVES:
I. Correlate molecular and inflammatory signature of primary tumors with response rate as well as changes in mutational burden in partial or non-responding tumors.
II. Determine changes in serum biomarkers associated with actionable targets as well as inflammatory signaling to evaluate feasibility and accuracy of serum protein analysis.
III. Determine changes in sentinel lymph node disease burden and subsequent rates of locoregional disease control, recurrence-free survival, melanoma specific survival and overall survival.
IV. Correlate molecular signature, immune phenotype and pattern of response in injected lesions to recurrence rate.
OUTLINE:
Patients receive T-VEC intratumorally (IT) over 30 minutes on days 1, 21, 35, and 49. Patients then undergo surgical resection of the tumor on day 56.
After completion of study treatment, patients are followed up at day 28 or 30, then every 3-6 months up to 24 months. If the patient discontinues treatment without disease progression, they are followed for 100 days.
Eligibility
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
- Karnofsky Performance Status (KPS) of 60% or greater
- Life expectancy >= 3 months
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelet count >= 75 x 10^9/L
- Hemoglobin >= 8 g/dL (may have been transfused)
- Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range
- Aspartate transaminase (AST) and alanine transferase (ALT) levels =< 2.5 x ULN or AST and ALT levels =< 5 x ULN (for subjects with documented metastatic disease to the liver)
- International normalized ratio (INR) and activated partial thromboplastin time (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 > 2.0 mm in depth with residual tumor or local, in-transit, or dermal oligometastatic resectable recurrence in a treatment-naive patient not otherwise eligible for systemic therapy
- Residual pigmented cutaneous lesion accessible to intralesional injection
Treatment Sites in Georgia
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