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TVEC and Preop Radiation for Sarcoma (4 ml Dose)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02453191
Recruitment Status : Active, not recruiting
First Posted : May 25, 2015
Results First Posted : June 17, 2020
Last Update Posted : May 3, 2021
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Varun Monga, MD, University of Iowa

Tracking Information
First Submitted Date  ICMJE April 28, 2015
First Posted Date  ICMJE May 25, 2015
Results First Submitted Date  ICMJE May 13, 2020
Results First Posted Date  ICMJE June 17, 2020
Last Update Posted Date May 3, 2021
Actual Study Start Date  ICMJE July 13, 2015
Actual Primary Completion Date January 22, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 2, 2020)
  • Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: 14 weeks ]
    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.
  • Phase 2: Number of Subjects With Pathologic Tumor Necrosis ≥ 95% Following Concurrent Radiation Therapy and Talimogene Laherparepvec. [ Time Frame: 14 weeks ]
    At the end of the neoadjuvant therapy, patients will undergo resection of the treated tumor. The percentage of post treatment tumor necrosis must be documented. The primary end point for this study is pathologic complete response (pCR), and is defined as ≥ 95% tumor necrosis following concurrent radiation therapy and talimogene laherparepvec.
Original Primary Outcome Measures  ICMJE
 (submitted: May 20, 2015)
  • 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 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2020)
  • Overall Response Rate (ORR) as Measured by RECIST [ Time Frame: 24 months ]
    Overall response rate (ORR) as measured by RECIST 1.1. Complete response is the disappearance of all target lesions.Partial response is a 30% decrease in the sum of the longest dimensions of the target lesions, relative to baseline. Progressive disease is an increase of 20% or more in the sum of the longest dimension of target lesions. Stable disease is a decrease in the tumor size of < 30% or an increase of < 20%..
  • Time to Disease Progression (TTP) [ Time Frame: 24 months ]
    TTP is defined as the time from enrollment until objective tumor progression including local and distant recurrences as measured by RECIST 1.1. Complete response is the disappearance of all target lesions.Partial response is a 30% decrease in the sum of the longest dimensions of the target lesions, relative to baseline. Progressive disease is an increase of 20% or more in the sum of the longest dimension of target lesions. Stable disease is a decrease in the tumor size of < 30% or an increase of < 20%.
  • Overall Survival Rate (OS) at 5 Years [ Time Frame: 5 years ]
    Subjects will be followed for overall survival rate (OS) at 5 years from the last enrollment
  • Number of Participants With Adverse Events (AEs) [ Time Frame: 14 weeks ]
    To further assess the safety of talimogene laherparepvec given concurrently with preoperative external beam radiation in sarcoma patients.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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2015)
  • 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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TVEC and Preop Radiation for Sarcoma (4 ml Dose)
Official Title  ICMJE Neoadjuvant Intralesional Injection of Talimogene Laherparepvec With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas
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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Soft Tissue Sarcoma
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: Treatment

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

Interventions:
  • Drug: Talimogene Laherparepvec
  • Radiation: Radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 15, 2019)
30
Original Estimated Enrollment  ICMJE
 (submitted: May 20, 2015)
32
Estimated Study Completion Date  ICMJE October 16, 2023
Actual Primary Completion Date January 22, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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 -

    1. Positive HBV surface antigen (indicative for chronic hepatitis B or recent acute hepatitis B).
    2. 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 -

    1. Positive HCV antibody and positive HCV RNA by PCR (undetectable RNA copies suggest past and resolved hepatitis C infection).

  • 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.
  • 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. See Section 7.5 for more details.
  • 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).
  • Other investigational procedures while participating in this study that could affect the primary objective of the study as determined by the PI are excluded.
  • Subject previously has entered this study.
  • Patients who are receiving any other investigational agents.
  • Evidence of CNS metastases.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to talimogene laherparepvec.
  • 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.
  • Patients on or requiring immunosuppressive therapies.
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02453191
Other Study ID Numbers  ICMJE 201504731 (4 milliliter dose)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Varun Monga, MD, University of Iowa
Study Sponsor  ICMJE University of Iowa
Collaborators  ICMJE Amgen
Investigators  ICMJE
Principal Investigator: Varun Monga, MD University of Iowa
PRS Account University of Iowa
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP