ClinicalTrials.gov

History of Changes for Study: NCT02453191
TVEC and Preop Radiation for Sarcoma
Latest version (submitted May 4, 2022) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 May 20, 2015 None (earliest Version on record)
2 August 11, 2015 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 April 5, 2016 Study Status, Eligibility and Outcome Measures
4 February 2, 2017 Study Status
5 April 21, 2017 Study Status and Sponsor/Collaborators
6 March 20, 2018 Study Status, Oversight and IPDSharing
7 March 15, 2019 Recruitment Status, Study Status, Contacts/Locations, Study Design and Document Section
Show
Results Submission Events
8 June 2, 2020 Outcome Measures, Study Status, Sponsor/Collaborators, Results and Contacts/Locations
9 October 20, 2020 Outcome Measures, Arms and Interventions, Document Section, Study Status, Study Identification, Eligibility and Study Description
10 April 30, 2021 Study Status
11 May 4, 2022 Study Status
Comparison Format:

Scroll up to access the controls

Study NCT02453191
Submitted Date:  May 20, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: 201504731
Brief Title: TVEC and Preop Radiation for Sarcoma
Official Title: Neoadjuvant Intralesional Injection of Talimogene Laherparepvec With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2015
Overall Status: Not yet recruiting
Study Start: May 2015
Primary Completion: April 2017 [Anticipated]
Study Completion: April 2018 [Anticipated]
First Submitted: April 28, 2015
First Submitted that
Met QC Criteria:
May 20, 2015
First Posted: May 25, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
May 20, 2015
Last Update Posted: May 25, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Milhem, Mohammed M
Responsible Party: Sponsor-Investigator
Investigator: Milhem, Mohammed M
Official Title: Clinical Professor, Internal Medicine, Hematology, Oncology and Blood & Marrow Transplantation
Affiliation: University of Iowa
Collaborators: Amgen
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

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.

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.
Open or close this module Conditions
Conditions: Soft Tissue Sarcoma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 32 [Anticipated]
Open or close this module Arms and Interventions
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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
2. 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 locally advanced high grade soft tissue sarcomas. For this study, pCR will be defined as ≥ 95% tumor necrosis following concurrent radiation therapy and talimogene laherparepvec.
Secondary Outcome Measures:
1. Overall response rate (ORR) as measured by RECIST 1.1 or a later tool for monitoring disease progression
[ Time Frame: 24 months ]

2. Time to progression
[ Time Frame: 24 months ]

3. Overall survival rate (OS) at 5 years
[ Time Frame: 5 years ]

4. 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).
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Subject or subject's legally acceptable representative 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.
    • 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
Open or close this module Contacts/Locations
Central Contact Person: Mohammed Milhem, MD
Telephone: 319-356-2324
Email: mohammed-milhem@uiowa.edu
Study Officials: Mohammed Milhem, MD
Principal Investigator
University of Iowa
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services