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Clinical Trial 19414

Cancer Type: Sarcoma
Interventions:Talimogene Laherparepvec (OncoVEX); Talimogene laherparepvec 10^6 PFU (Talimogene Laherparepvec); Talimogene laherparepvec 10^8 PFU (Talimogene Laherparepvec)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Mihaela Druta

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

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

Summary

his 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. 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.

Objective

1.1 Primary Objectives 1.1.1 To estimate the pathologic complete necrosis rate (the number of patients with ¡Ý 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. 1.2 Secondary Objectives 1.2.1 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. 1.2.2 To estimate the rate of radiologic response, prior to surgery, and extent of surgical resection. 1.2.3 To estimate time to surgery, time to progression, time to recurrence, and death. 1.3 Correlative Objectives 1.3.1 To characterize the clinical outcomes within three distinct histologic subtypes: liposarcoma (excluding myxoid liposarcoma), leiomyosarcoma and undifferentiated pleomorphic sarcoma. 1.3.2 To characterize the percentage of tumor necrosis in treated tumors. 1.3.3 To assess if the combination of preoperative talimogene laherparepvec (T-VEC) with radiation will increase the expression of PD-L1 in soft tissue sarcomas. 1.3.4 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.

Inclusion Criteria

  • Participant has been confirmed (through the protocol specified central review process to have newly diagnosed and a histopathologically potentially resectable soft tissue sarcoma of the extremity or trunk of the following subtypes:
  • Participant must have a histologically determined grade 2 or 3 tumor (through the protocol specified central review process) by the French Federation of Comprehensive Cancer Centers (FNCLCC) sarcoma grading system
  • Participants must have localized disease with a primary tumor >= 5 cm by magnetic resonance imaging (MRI) or computed tomography (CT) scan
  • Participants 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
  • Participants must have a sarcoma in the extremity or trunk in location, which is accessible to direct or ultrasound guided injections
  • Participant must have a life expectancy of at least 3 months with appropriate therapy
  • Participants must agree to use contraception during study treatment and for 4 months after the end of treatment

  • Exclusion Criteria

  • Participants 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)
  • Participants who have had prior treatment with anti-PD1 or anti-CTLA4 therapy
  • Participants with grade 1 non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) tumors of any size are not eligible
  • Participants with evidence of active bleeding or bleeding diathesis will be excluded (participants with excess of 2.5 mL of hemoptysis are not eligible)
  • Participants requiring therapeutic anticoagulation
  • Participants must have had no prior radiotherapy to tumor-involved sites
  • Participants with gross total resection of the primary tumor prior to enrollment are not eligible; participants who have experienced tumor recurrence after gross total tumor resection are not eligible
  • History of serious or non-healing wound, ulcer, or bone fracture
  • Participants 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
  • Participants 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)
  • 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 HIV
  • Prior therapy with viral-based tumor vaccine
  • Received live vaccine within 28 days prior to enrollment
  • Participants 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
  • Participants who are pregnant, breastfeeding or plan to become pregnant