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TVEC and Preop Radiation for Sarcoma

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Mohammed M Milhem, University of Iowa
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Mohammed M Milhem, University of Iowa
ClinicalTrials.gov Identifier:
NCT02453191
First received: April 28, 2015
Last updated: April 21, 2017
Last verified: April 2017
  Purpose

The purpose of this research study is to determine the safety and tolerability of talimogene laherparepvec when combined with radiation therapy.

Approximately 32 people will take part in this study conducted by investigators at the University of Iowa.


Condition Intervention Phase
Soft Tissue Sarcoma Drug: talimogene laherparepvec Radiation: Radiotherapy Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Neoadjuvant Intralesional Injection of Talimogene Laherparepvec With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas

Resource links provided by NLM:


Further study details as provided by Mohammed M Milhem, University of Iowa:

Primary Outcome Measures:
  • Phase 1b: To determine the safety and tolerability of neoadjuvant talimogene laherparepvec in combination with preoperative EBRT [ Time Frame: 14 weeks ]
    Phase 1b: To determine the safety and tolerability of neoadjuvant talimogene laherparepvec in combination with preoperative EBRT as assessed by incidence of dose-limiting toxicities (DLT) in subjects with locally advanced high grade soft tissue sarcomas.

  • Phase 2: To estimate the efficacy of neoadjuvant talimogene laherparepvec and radiotherapy [ Time Frame: 14 weeks ]
    To estimate the efficacy of neoadjuvant talimogene laherparepvec and radiotherapy as assessed by the pathological complete response rates (pCR) in subjects with histologically confirmed diagnosis of locally advanced STS that is unresectable with clear wide margins, for which preoperative radiotherapy is considered appropriate.


Secondary Outcome Measures:
  • Overall response rate (ORR) as measured by RECIST 1.1 or a later tool for monitoring disease progression [ Time Frame: 24 months ]
  • Time to progression [ Time Frame: 24 months ]
  • Overall survival rate (OS) at 5 years [ Time Frame: 5 years ]
  • Patients will be monitored for adverse events to assess the safety of talimogene laherparepvec [ Time Frame: 24 months ]
    Information regarding the occurrence of adverse events will be collected from the time the subject signs the informed consent form and throughout their participation in the study, including a period of 30 days after the last dose of study drug (data on serious adverse events (SAEs) will be collected until resolution of the event unless otherwise noted).


Estimated Enrollment: 32
Study Start Date: July 2015
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
talimogene laherparepvec in combination with radiotherapy
Drug: talimogene laherparepvec
talimogene laherparepvec
Radiation: Radiotherapy
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.

Detailed Description:
This is a single-arm open-label phase Ib and phase II clinical study assessing the safety and relative efficacy of concurrent talimogene laherparepvec in combination with radiotherapy in patients with soft tissue sarcomas. Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec. Weekly injections of talimogene laherparepvec will be continued until surgery. Surgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject has provided informed consent.
  2. 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.
  3. 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.
  4. Age ≥18 years.
  5. Both men and women of all races and ethnic groups are eligible for this trial.
  6. ECOG performance status ≤1.
  7. 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.

7.1 Patient must have injectable disease (direct injection or ultrasound guided).

Exclusion Criteria:

  1. Certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma, and bone sarcomas
  2. History or evidence of sarcoma associated with immunodeficiency states (e.g.: Hereditary immune deficiency, HIV, organ transplant or leukemia).
  3. Subjects with retroperitoneal and visceral sarcoma.
  4. 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).
  5. 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.
  6. History of prior or current autoimmune disease.
  7. History of prior or current splenectomy or splenic irradiation.
  8. Active herpetic skin lesions.
  9. Require intermittent or chronic treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use.
  10. Any non-oncology vaccine therapies used for the prevention of infectious disease within 28 days prior to enrollment and during treatment period.
  11. Concomitant treatment with therapeutic anticoagulants such as warfarin.
  12. Known human immunodeficiency virus (HIV) disease (requires negative test for clinically suspected HIV infection).
  13. 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).
      • Negative HBV surface antigen but positive HBV total core antibody (indicative for resolved hepatitis B infection or occult hepatitis B) and detectable copies of HBV DNA by PCR (detectable HBV DNA copies suggest occult hepatitis B).
    • Evidence of hepatitis C -

      • Positive HCV antibody and positive HCV RNA by PCR (undetectable RNA copies suggest past and resolved hepatitis C infection).
  14. Female subjects who are pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of study treatment.
  15. Female subjects of childbearing potential or male subjects who are unwilling to use 2 highly effective methods of contraception during study treatment and through 3 months after the last dose of study treatment.
  16. Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).
  17. Other investigational procedures while participating in this study are excluded.
  18. Subject previously has entered this study.
  19. Patients who are receiving any other investigational agents.
  20. Evidence of CNS metastases.
  21. History of allergic reactions attributed to compounds of similar chemical or biologic composition to talimogene laherparepvec.
  22. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  23. Patients on or requiring immunosuppressive therapies.
  24. Any of the following laboratory abnormalities:

    • Hemoglobin < 9.0 g/dL
    • Absolute neutrophil count (ANC) < 1500 per mm3
    • Platelet count < 100,000 per mm3
    • Total bilirubin > 1.5 × ULN
    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN
    • Alkaline phosphatase > 2.5 × ULN
    • PT (or INR) and PTT (or aPTT) > 1.5 × ULN
    • Creatinine > 2.0 × ULN
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02453191

Contacts
Contact: Mohammed Milhem, MD 319-356-2324 mohammed-milhem@uiowa.edu

Locations
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Mohammed Milhem, MD    319-356-2324    mohammed-milhem@uiowa.edu   
Sponsors and Collaborators
Mohammed M Milhem
Amgen
Investigators
Principal Investigator: Mohammed Milhem, MD University of Iowa
  More Information

Responsible Party: Mohammed M Milhem, Clinical Professor, Internal Medicine, Hematology, Oncology and Blood & Marrow Transplantation, University of Iowa
ClinicalTrials.gov Identifier: NCT02453191     History of Changes
Other Study ID Numbers: 201504731
Study First Received: April 28, 2015
Last Updated: April 21, 2017

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on June 23, 2017