Neoplasms

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Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

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Histiocytoma, Malignant Fibrous

Leiomyosarcoma

Histiocytoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Adipose Tissue

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Talimogene laherparepvec

Antineoplastic Agents, Immunological

Patients receive talimogene laherparepvec 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 MRI throughout the trial.

Biopsy

Biospecimen Collection

Magnetic Resonance Imaging

Radiation Therapy

Talimogene Laherparepvec

Steven I Robinson

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.

Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery

A Phase 2 Study of Talimogene Laherparepvec (T-VEC) and Radiation in Localized Soft Tissue Sarcoma

Summary statistics and frequency tables will be used to describe tumor necrosis. T-tests, logistic regression, and non-parametric methods, if required, may be used.

Will be defined as \>= 95% of tumor having necrosis. The estimated pathologic CR rate and a 95% confidence interval will be reported.

Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

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.

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.

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.

Will be estimated using Kaplan-Meier methodology.

Will be estimated using Kaplan-Meier methodology in only those patients having achieved a complete surgical resection.

Spots Global Cancer Trial Database for soft tissue sarcoma of the trunk and extremities