TVEC and Preop Radiation for Sarcoma (4 ml Dose)

NCT02453191 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 201504731 (4 milliliter dose)
• Study Type: interventional
• Target: 30
• 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 30 people will take part in this study conducted by investigators at the University of Iowa.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Number of Subjects 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

• Phase 2: Pathologic Tumor Necrosis Rate

  Pathologic tumor necrosis rate is defined as the percentage of subjects with pathologic tumor necrosis ≥ 95%.

  14 weeks

Secondary Outcomes (4)

• Overall Response Rate

  24 months

• Percentage of Participants With 2 Year Progression-Free Survival

  24 months

• Percentage of Participants With 2 Year Overall Survival

  24 months

• Number of Participants With Adverse Events (AEs)

  14 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Talimogene Laherparepvec in combination with radiotherapy Talimogene Laherparepvec Dose Levels: • Initial dose for all = talimogene laherparepvec up to 4.0 mL of 106 PFU/mL

Drug: Talimogene Laherparepvec; Radiation: Radiotherapy

Interventions

Talimogene Laherparepvec DRUG

Talimogene Laherparepvec

Treatment

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.

Treatment

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, and bone sarcomas.
• 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, and bone sarcomas.
• 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.
• 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

• University of Iowa: lead
• Amgen: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (1)

• Monga V, Miller BJ, Tanas M, Boukhar S, Allen B, Anderson C, Stephens L, Hartwig S, Varga S, Houtman J, Wang L, Zhang W, Jaber O, Thomason J, Kuehn D, Rajput M, Metz C, Zamba KD, Mott S, Abanonu C, Bhatia S, Milhem M. Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial. J Immunother Cancer. 2021 Jul;9(7):e003119. doi: 10.1136/jitc-2021-003119.

  PMID: 34330766 DERIVED

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

Results Point of Contact

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

varun-monga@uiowa.edu

319-384-9497

Study Officials

• John Rieth, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 28, 2015
• First Posted: May 25, 2015
• Study Start: July 13, 2015
• Primary Completion: January 22, 2019
• Study Completion: March 10, 2023
• Last Updated: June 20, 2024
• Results First Posted: June 17, 2020

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)