This phase II trial studies the side effects of talimogene laherparepvec and radiation therapy and to see how well they work in treating patients with newly diagnosed soft tissue sarcoma that can be removed by surgery (resectable). Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Radiation therapy uses high energy x-rays, photons. electrons, or protons to kill tumor cells and shrink tumors. Giving talimogene laherparepvec and radiation therapy may work better in treating patients with soft tissue sarcoma.
PRIMARY OBJECTIVE: I. To estimate the pathologic complete necrosis rate (the number of patients with \>= 95% necrosis divided by the number of evaluable patients) following preoperative treatment with talimogene laherparepvec (T-VEC) in combination with radiation in patients with localized soft tissue sarcoma including a pre-planned interim safety analysis to assess post-surgical wound complications. SECONDARY OBJECTIVES: I. To estimate the toxicity of talimogene laherparepvec (T-VEC) in combination with radiation in localized soft tissue sarcomas, during neo-adjuvant treatment and post-surgical resection wound complications. II. To estimate the rate of radiologic response, prior to surgery, and extent of surgical resection. III. To estimate time to surgery, time to progression, time to recurrence, and death. CORRELATIVE OBJECTIVES: I. To characterize the clinical outcomes within three distinct histologic subtypes: liposarcoma (excluding myxoid liposarcoma), leiomyosarcoma and undifferentiated pleomorphic sarcoma. II. To characterize the percentage of tumor necrosis in treated tumors. III. To assess if the combination of preoperative talimogene laherparepvec (T-VEC) with radiation will increase the expression of PD-L1 in soft tissue sarcomas. IV. To assess the impact of preoperative talimogene laherparepvec (T-VEC) with radiation on the tumor infiltrating and circulating immune cells in patients with soft tissue sarcomas. OUTLINE: Patients receive talimogene laherparepvec intratumorally (IT) or via intralesional injection at weeks 1, 4, 6 and 8. Beginning 1 week after the start of talimogene laherparepvec, patients undergo radiation therapy on Monday-Friday of weeks 2-6. Patients undergo collection of blood and a tumor biopsy on study and undergo magnetic resonance imaging (MRI) throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then every year for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Undergo tumor biopsy
Undergo collection of blood
Undergo MRI
Undergo radiation therapy
Given IT or via intralesional injection
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
...and 7 more locations
Pathologic complete response (CR) rate
Will be defined as \>= 95% of tumor having necrosis. The estimated pathologic CR rate and a 95% confidence interval will be reported.
Time frame: Up to 5 years
Incidence of post-surgical wound complications
Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Up to 4 months post-surgery
Incidence of toxicities of T-VEC in combination with radiation therapy
Will be evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Summary statistics and frequency tables will be used to describe the distributions of the observed adverse events occurring pre-surgery and following surgery. All patients having initiated study treatment will be considered evaluable for toxicity analysis.
Time frame: Up to 5 years
Rate of radiologic response
Will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Estimates and confidence intervals will be used to summarize the observed rate of radiologic response.
Time frame: Up to 5 years
Rate of surgical response
Will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Estimates and confidence intervals will be used to summarize the observed rate of surgical response.
Time frame: Up to 5 years
Time to surgery
Will be estimated using Kaplan-Meier methodology.
Time frame: From registration date until surgery, assessed up to 5 years
Time to progression
Will be estimated using Kaplan-Meier methodology.
Time frame: From registration date until disease progression, assessed up to 5 years
Time to recurrence
Will be estimated using Kaplan-Meier methodology in only those patients having achieved a complete surgical resection.
Time frame: From registration date until disease recurrence, assessed up to 5 years
Time to death
Will be estimated using Kaplan-Meier methodology.
Time frame: From registration date until death, assessed up to 5 years
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