Basal cell carcinoma (BCC) is the most common malignant neoplasm in fair skinned humans (Rubin et al., 2005). Over the last decades its incidence has increased (Chinem and Miot, 2011). Especially when it comes to BCCs of intermediate size, a surgical approach, while still feasible is often associated with complications and often requires major reconstructive surgery with a suboptimal cosmetic outcome. We hypothesize that neoadjuvant Talimogene laherparepvec minimizes the size of the BCC.
Conditions
Interventions
Trade Name: Imlygic Talimogene Laherparepvec
Product Name: Talimogene laherparepvec (Imlygic)
Pharmaceutical Form: Solution for injection
INN or Propose
Sponsors
Medical University Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Subject has provided informed consent prior to initiation of any study-specific activities/procedures 2) Male or female age = 18 years at the time of informed consent 3) BCC, excluding superficial and sclerodermiform BCC either newly developed or recurring/progressing after prior treatment; In clinically suspected BCCs, without a prior histopathological confirmation, the confirmation with the baseline biopsy is sufficient 4) Subjects have to be willing to undergo a tumor biopsy at baseline 5) The tumor has to be assessed by an expert panel (see section 8.1.1.) as being locally advanced but resectable if reconstructive plastic surgery (i.e. flap or skin graft) is used for wound closure 6) Tumors must be measurable by caliper 7) ECOG Performance Status 0 8) Adequate hematological, renal, hepatic and coagulation function within 14 days prior to enrollment 9) Any systemic therapy for advanced BCC must have been stopped at least 8 weeks before study treatment and patients must have recovered from any acute toxicity associated with prior therapy 10) Life expectancy of more than three months 11) Female Subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to enrollment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1) Metastatic BCC 2) History of any other malignancy within the past 3 years with the following exceptions: • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease • Adequately treated cervical carcinoma in situ without evidence of disease • Adequately treated breast ductal carcinoma in situ without evidence of disease • Prostatic intraepithelial neoplasia without evidence of prostate cancer • Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ 3) Active infection (herpetic skin lesions, or prior complications of herpetic infection, HIV, Hep A, B, C) 4) Previous treatment with T-VEC or any other oncolytic virus 5) Prior therapy with tumor vaccines, chemotherapy, radiotherapy, biological cancer therapy, targeted therapy < 28 days prior to enrollment 6) Any concurrent medical condition requiring the use of systemic steroids or antiviral drugs 7) History or evidence of active autoimmune disease that requires systemic treatment (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment 8) Evidence of clinically significant immunosuppression 9) Any underlying medical condition which, in the Investigator's opinion, will make the administration of study drugs hazardous or obscure the interpretation of Adverse Events 10) Female Subjects who are pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of T-VEC 11) Sexually active Subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with T-VEC 12) Female Subjects of childbearing potential who are unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of T-VEC 13) Live vaccines within 28 days prior to enrollment 14) Major surgery prior to enrollment 28 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the number of patients with a BCC that become resectable with primary wound closure without the need for plastic reconstructive surgery like skin flaps or skin grafts. Hypothesis: H0: < 25% of “difficult to resect” laBCC become resectable without the need for plastic reconstruction H1: = 25% of “difficult to resect” laBCC become resectable without the need for plastic reconstruction ; Secondary Objective: - To assess the safety of T-VEC in patients with locally advanced BCC - To assess relapse free survival, defined as the time from complete resection of any residual tumor until local recurrence, in patients with locally advanced BCC under neoadjuvant treatment with T-VEC - To assess relapse free survival rate (RFS) - To assess the rate of appearance of BCCs on other body sites during the follow up period - To assess the biological read outs in respect to tumor related immunity before and after therapy in biopsy samples ; Primary end point(s): - The number of patients with a BCC that become resectable with primary wound closure without the need for plastic reconstructive surgery like skin flaps or skin grafts Null and alternative hypotheses: H0: < 25% of “difficult to resect” laBCC become resectable without the need for plastic reconstruction H1: = 25% of “difficult to resect” laBCC become resectable without the need for plastic reconstruction ;Timepoint(s) of evaluation of this end point: Stage I after one year, and Stage II after two years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - RFS, defined as the time from complete resection of any residual tumor until recurrence, - Biological difference of immunological read outs at baseline and after therapy in tumor samples - Incidence of local relapse - Time of appearence of a new BCC in any other site of the body ;Timepoint(s) of evaluation of this end point: after 3 years | — |
Countries
Austria
Contacts
Public ContactJulia Ressler
Medical University Vienna
Outcome results
None listed