TVEC and Preop Radiation for Sarcoma (8 ml Dose)

NCT04599062 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: 201504731 (8 milliliter dose)
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the safety and tolerability of talimogene laherparepvec when combined with radiation therapy. Approximately 46 people will take part in this study conducted by investigators at the University of Iowa.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  A DLT is defined as any of the following talimogene laherparepvec-related toxicity or related to the combination of talimogene laherparepvec and radiation therapy during treatment and up to 4 weeks after the last talimogene laherparepvec injection: Grade 3 or greater immune-mediated adverse events, Grade 3 or greater allergic reactions, any grade plasmacytoma, any other unexpected grade 3 or greater hematologic or non-hematologic toxicity, with the exceptions of: any grade of alopecia, expected radiation related skin toxicity of any grade, Grade 3 arthralgia or myalgia, brief (\< 1 week) grade 3 fatigue, Grade 3 fever, Grade 3 diarrhea or vomiting responding to supportive case.

  14 weeks

• Pathologic Tumor Necrosis Rate

  Pathologic tumor necrosis rate is defined as the percentage of subjects with pathologic tumor necrosis ≥ 90%.

  14 weeks

Secondary Outcomes (3)

• Overall Response Rate

  24 months

• 2 Year Progression-Free Survival

  24 months

• 2 Year Overall Survival

  24 months

Study Arms (2)

Talimogene Laherparepvec in combination with radiotherapy-Phase I Cohort

EXPERIMENTAL

Talimogene Laherparepvec Dose Levels: Dose 0 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed weekly Dose -1 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed every 2 weeks

Drug: Talimogene Laherparepvec; Radiation: Radiotherapy

Talimogene Laherparepvec in combination with radiotherapy-Phase II Cohort

ACTIVE COMPARATOR

Dose 0 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed weekly

Drug: Talimogene Laherparepvec; Radiation: Radiotherapy

Interventions

Radiotherapy RADIATION

Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.

Talimogene Laherparepvec in combination with radiotherapy-Phase I Cohort; Talimogene Laherparepvec in combination with radiotherapy-Phase II Cohort

Talimogene Laherparepvec DRUG

Talimogene Laherparepvec

Talimogene Laherparepvec in combination with radiotherapy-Phase I Cohort; Talimogene Laherparepvec in combination with radiotherapy-Phase II Cohort

Eligibility Criteria

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

You may qualify if:

• Subject has provided informed consent.
• Histologically confirmed diagnosis of locally advanced STS that is unresectable with clear wide margins, for which preoperative radiotherapy is considered appropriate.
• EXAMPLES:
• Resectable stage IIB, III, and IV disease that are not suitable for surgically resection alone due to inability to achieve clear margins.
• Including metastatic (stage IV) disease for which radiotherapy and surgical resection are indicated.
• Except certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma, bone sarcomas and myxoid liposarcomas (Grade 1).
• Previous treatment: prior systemic anti-cancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy are allowed provided therapy completed at least 1 year prior to enrollment.
• No prior Talimogene laherparepvec or tumor vaccines allowed.
• No prior radiation to the same tumor bed allowed.
• Age ≥18 years.
• Both men and women of all races and ethnic groups are eligible for this trial.
• ECOG performance status ≤1.
• Patient must have measurable disease:
• Tumor size at least ≥ 5 cm in the longest diameter as measured by CT scan or MRI for which radiation is feasible.
• Patient must have injectable disease (direct injection or ultrasound guided).

You may not qualify if:

• Certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma bone sarcomas and low grade myxoid liposarcomas ( Grade 1).
• History or evidence of sarcoma associated with immunodeficiency states (e.g.: Hereditary immune deficiency, HIV, organ transplant or leukemia).
• Subjects with retroperitoneal and visceral sarcoma.
• History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn's disease) or other symptomatic autoimmune disease including, inflammatory bowel disease, or history of any poorly controlled or severe systemic autoimmune disease (i.e., rheumatoid arthritis, systemic lupus erythematosus, scleroderma, type I diabetes, or autoimmune vasculitis).
• History of other malignancy within the past 3 years except treated with curative intent and no known active disease present and has not received chemotherapy for ≥ 1 year before enrollment/randomization and low risk for recurrence.
• History of prior or current autoimmune disease.
• History of prior or current splenectomy or splenic irradiation.
• Active herpetic skin lesions
• Require intermittent or chronic treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use.
• Any non-oncology vaccine therapies used for the prevention of infectious disease within 28 days prior to enrollment and during treatment period.
• Concomitant treatment with therapeutic anticoagulants such as warfarin. Patients on therapeutic low molecular weight heparin may be allowed provided the dose can be safely held as per the treating investigator on the morning of scheduled intratumoral injection and can be resumed 12 hours after the procedure
• Known human immunodeficiency virus (HIV) disease (requires negative test for clinically suspected HIV infection).
• Acute or chronic hepatitis B or hepatitis C infection (requires negative test for clinically suspected hepatitis B or hepatitis C infection).
• Evidence of hepatitis B -
• Positive HBV surface antigen (indicative for chronic hepatitis B or recent acute hepatitis B).

Sponsors & Collaborators

• Amgen: collaborator
• John Rieth: lead

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

talimogene laherparepvec; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Limitations and Caveats

Enrollment halted prematurely due to funding. Participants are being followed for secondary outcome measures.

Results Point of Contact

• Title: Varun Monga, MD
• Organization: University of Iowa, Holden Comprehensive Cancer Center

varun-monga@uiowa.edu

319-384-9497

Study Officials

• John Rieth, MD

  University of Iowa Holden Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: October 22, 2020
• Study Start: September 10, 2020
• Primary Completion: February 7, 2023
• Study Completion (Estimated): February 16, 2028
• Last Updated: January 29, 2026
• Results First Posted: June 22, 2023

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)