Clinical trial NCT03842943: Neoadjuvant Combination Immunotherapy for Stage III Melanoma
Official title: Neoadjuvant Combination Immunotherapy for Stage III Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cutaneous Melanoma
Lead sponsor: University of Louisville
Sponsor class: OTHER
First posted: 2019-02-15
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Determine safety and efficacy of pre-operative combination immunotherapy with Talimogene Laherparepvec (T-VEC)/Pembrolizumab given prior to complete lymph node dissection in resectable stage 3 cutaneous melanoma with clinically apparent lymph node metastases.

Detailed description: This is a single arm Phase 2 study of pre-operative combination immunotherapy with pembrolizumab and T-VEC given for 6 months prior to complete lymph node dissection for stage 3 resectable cutaneous melanoma with clinically apparent lymph node metastases.

Eligibility criteria: Inclusion Criteria:

* 18 years of age, any race or sex, who have pathologically confirmed cutaneous melanoma
* ECOG performance status of 0 or 1
* Adequate hematologic, hepatic, renal and coagulation function
* Must have measurable disease and have an injectable target lymph node for intralesional therapy administration
* Primary melanoma has been resected
* Pathologically confirmed resectable stage III disease, clinically apparent. Resectability is at the discretion of the treating surgeon who is a melanoma specialist.
* Stage III disease can be at time of diagnosis of primary melanoma or a recurrence after initial treatment of stage I-II disease.
* BRAF mutant or wild type allowed (mutations status not necessary for enrollment)
* Signed, written informed consent

Exclusion Criteria:

* Cannot have metastatic (AJCC M1) disease
* No primary mucosal or uveal melanoma
* No evidence of melanoma associated with immunodeficiency state or history or other malignancies (other than non-melanoma skin cancer) within the past 3 years
* May not have been previously treated with T-VEC, any other oncolytic virus, pembrolizumab, or any other PD-1, PD-L1, or PD-L2 inhibitor
* Must not have a history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, document history of autoimmune disease or syndrome requiring systemic treatment in the past two years (i.e. use of disease modifying agents, steroids, or immunosuppressive agents) except vitiligo or resolved childhood asthma/atopy, or evidence of clinically significant immunosuppression
* Must not have active herpetic skin lesions or prior complications of herpetic infection and must not require intermittent or chronic treatment with an anti-herpetic drug (e.g. acyclovir) other than intermittent topical use

Primary outcomes:
measure: Pathologic Complete Response
timeFrame: 6 months
Secondary outcomes:
measure: Safety and Tolerability of Preoperative T-VEC/pembrolizumab: Adverse events and Serious Adverse Events
timeFrame: Every 3-6 weeks during the combination treatment period, and every 3 months after surgery through study completion, up to 5 years
Other outcomes:
Locations:
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
Study officials:
affiliation: University of Louisville
name: Michael Egger, MD
role: PRINCIPAL_INVESTIGATOR
References: