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

NCT02923778 | Active Not Recruiting Phase 2 FDA Drug

• 4 other identifiers: NCI-2016-01461MC167810056UM1CA186686
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 17

Brief Summary

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.

Conditions

Sarcoma G3; Soft Tissue Sarcoma; Stage I Soft Tissue Sarcoma AJCC v7; Liposarcoma; Sarcoma G2; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma; Soft Tissue Sarcoma of the Trunk and Extremities; Stage II Soft Tissue Sarcoma AJCC v7

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 4 months post-surgery

Secondary Outcomes (7)

• Incidence of toxicities of T-VEC in combination with radiation therapy

  Up to 5 years

• Rate of radiologic response

  Up to 5 years

• Rate of surgical response

  Up to 5 years

• Time to surgery

  From registration date until surgery, assessed up to 5 years

• Time to progression

  From registration date until disease progression, assessed up to 5 years

Other Outcomes (4)

• Clinical outcomes within liposarcoma, leiomyosarcoma, and undifferentiated pleomorphic sarcoma

  Up to 5 years

• Percentage of tumor necrosis in treated tumors

  Up to 5 years

• Change in PD-L1 expression

  Baseline to time of surgery

Study Arms (1)

Treatment (talimogene laherparepvec, radiation therapy)

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Radiation: Radiation Therapy; Biological: Talimogene Laherparepvec

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (talimogene laherparepvec, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (talimogene laherparepvec, radiation therapy)

Talimogene Laherparepvec BIOLOGICAL

Given IT or via intralesional injection

Also known as: ICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene, Imlygic, JS1 34.5-hGMCSF 47- pA-, T-VEC

Treatment (talimogene laherparepvec, radiation therapy)

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (talimogene laherparepvec, radiation therapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (talimogene laherparepvec, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• Note: Because no dosing or adverse event data are currently available on the use of talimogene laherparepvec (T-VEC) in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
• Newly diagnosed and a histopathologically confirmed potentially resectable soft tissue sarcoma of the extremity or trunk of the following subtypes:
• Cohort 1: liposarcoma (excluding myxoid liposarcoma)
• Cohort 2: leiomyosarcoma
• Cohort 3: undifferentiated pleomorphic sarcoma (UPS) (malignant fibrous histiosarcoma \[MFH\])
• NOTE: If local pathology report is suggestive of or suspicious for UPS, study chair and study pathologists may review for eligibility determination.
• NOTE: Sites permissible for biopsy include
• Extremities: upper (including shoulder) and lower (including hip)
• Trunk: Body wall
• Patients must have a histologically determined grade 2 or 3 tumor by the French Federation of Cancer Centers Sarcoma Group (FNCLCC) sarcoma grading system
• Patients must have localized disease with a primary tumor \> 5 cm by MRI or computed tomography (CT) scan
• Patients must have a primary tumor that is 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

You may not qualify if:

• 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 any therapeutic anticoagulation
• Patients must have had no prior radiotherapy to tumor-involved sites
• Patients with gross total resection of the primary tumor or who have developed tumor recurrence after gross total tumor resection prior to enrollment 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (17)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Goff PH, Riolobos L, LaFleur BJ, Spraker MB, Seo YD, Smythe KS, Campbell JS, Pierce RH, Zhang Y, He Q, Kim EY, Schaub SK, Kane GM, Mantilla JG, Chen EY, Ricciotti R, Thompson MJ, Cranmer LD, Wagner MJ, Loggers ET, Jones RL, Murphy E, Blumenschein WM, McClanahan TK, Earls J, Flanagan KC, LaFranzo NA, Kim TS, Pollack SM. Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells. Clin Cancer Res. 2022 Apr 14;28(8):1701-1711. doi: 10.1158/1078-0432.CCR-21-4239.

  PMID: 35115306 DERIVED

MeSH Terms

Conditions

Leiomyosarcoma; Liposarcoma; Sarcoma; Histiocytoma, Malignant Fibrous

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Radiotherapy; Radiation; talimogene laherparepvec

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Adipose Tissue; Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Therapeutics; Physical Phenomena

Study Officials

• Steven I Robinson

  Mayo Clinic Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2016
• First Posted: October 5, 2016
• Study Start: December 31, 2019
• Primary Completion (Estimated): December 29, 2026
• Study Completion (Estimated): December 29, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-01

Locations

US (16); CA (1)