Clinical Trials

Inclusion Criteria: 

• Newly diagnosed and histopathologically confirmed (by central pathology review) potentially resectable soft tissue sarcomas of the extremity and trunk of the following subtypes: liposarcoma (excluding myxoid liposarcoma), leiomyosarcoma and undifferentiated pleomorphic sarcoma - An incisional or core biopsy is the preferred method for diagnosis; fine needle aspiration is not acceptable.
• Sites permissible for biopsy include.
• Extremities: upper (including shoulder) and lower (including hip).
• Trunk: body wall.
• Patients must have localized disease with a primary tumor  ≥ 5 cm by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
• Patients must have histologically confirmed grade 2 or 3 tumors by the French Federation of Cancer Centers Sarcoma Group (FNCLCC) sarcoma grading system.
• Patients must have a primary tumor that are determined by multidisciplinary team (medical oncology, orthopedic/surgical oncology, and radiation oncology) to require radiation therapy for optimal management prior to surgical resection.
• Patients must have a sarcoma in the extremity or trunk in location, which is accessible to direct or ultrasound guided injections.
• Karnofsky performance score ≥ 70.
• Absolute neutrophil count (ANC) ≥ 1500/uL.
• Absolute lymphocyte count (ALC) ≥ 800/uL.
• Platelets ≥ 100,000/uL.
• Hemoglobin ≥ 9 g/dL.
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x institutional ULN.
• Calculated creatinine clearance > 70 mL/min/1.73 m^2.
• Patient must have a life expectancy of at least 3 months with appropriate therapy.
• Patients must agree to use contraception during study treatment and for 4 months after the end of treatment.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation, and for four months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to randomization and agree to use effective contraception throughout the treatment period and for 4 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.
• Willingness to provide mandatory tissue and blood samples for correlative studies.

Exclusion Criteria: 

• Patients with localized sarcomas that are not of the extremity or trunk wall (including head/neck, retroperitoneum, visceral organs, peritoneum, pelvis within the confines of the bony pelvis, and tumors arising in bone).
• Patients who have had prior treatment with anti-PD1 or anti-CTLA4 therapy.
• Patients with grade 1 non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) tumors of any size are not eligible.
• Patients with evidence of active bleeding or bleeding diathesis will be excluded (patients with excess of 2.5 mL of hemoptysis are not eligible).
• Patients requiring therapeutic anticoagulation.
• Patients must have had no prior radiotherapy to tumor-involved sites.
• Patients with gross total resection of the primary tumor prior to enrollment are not eligible; patients who have experienced tumor recurrence after gross total tumor resection are not eligible.
• History of serious or non-healing wound, ulcer, or bone fracture.
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1).
• Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of talimogene laherparepvec (T-VEC) and during the study.
• Previous treatment with talimogene laherparepvec (T-VEC) or any other oncolytic virus. Patients with metastatic disease.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to talimogene laherparepvec (T-VEC) or any of its components.
• History or evidence of active autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other); or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) within 2 months of enrollment; (replacement therapy [e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency] is not considered a form of systemic treatment for autoimmune disease).
• Evidence of clinically significant immunosuppression such as 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 2 months prior to enrollment.
• Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis).
• Viral infections requiring intermittent or chronic systemic (intravenous or oral) treatment with an anti-herpetic drug, other than intermittent topical use (e.g., acyclovir).
• Other viral infections.
• Known to have acute or chronic active hepatitis B or hepatitis C infection.
• Known to have human immunodeficiency virus (HIV) infection.
• Prior therapy with viral-based tumor vaccine.
• Received live vaccine within 28 days prior to enrollment - Patients who are unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for herpes simplex virus (HSV)-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec (T-VEC) treatment and through 30 days after the last dose of talimogene laherparepvec (T-VEC).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who are pregnant, breastfeeding or plan to become pregnant; sexually active patients and their partners must be willing to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation, and for four months after the last dose of T-VEC.