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Trial record 13 of 64 for:    Soft Tissue | "Dermatofibroma"

Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery

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ClinicalTrials.gov Identifier: NCT02923778
Recruitment Status : Suspended (Other - Additional pre-registration requirements needed.)
First Posted : October 5, 2016
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies the side effects of talimogene laherparepvec and radiation therapy and to see how well they work in treating patients with newly diagnosed soft tissue sarcoma that can be removed by surgery. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Radiation therapy uses high energy x-rays, photons. electrons, or protons to kill tumor cells and shrink tumors. Giving talimogene laherparepvec and radiation therapy may work better in treating patients with soft tissue sarcoma.

Condition or disease Intervention/treatment Phase
FNCLCC Sarcoma Grade 2 FNCLCC Sarcoma Grade 3 Leiomyosarcoma Liposarcoma Stage I Soft Tissue Sarcoma AJCC v7 Stage IA Soft Tissue Sarcoma AJCC v7 Stage IB Soft Tissue Sarcoma AJCC v7 Stage II Soft Tissue Sarcoma AJCC v7 Stage IIA Soft Tissue Sarcoma AJCC v7 Stage IIB Soft Tissue Sarcoma AJCC v7 Undifferentiated Pleomorphic Sarcoma Other: Laboratory Biomarker Analysis Radiation: Radiation Therapy Biological: Talimogene Laherparepvec Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the pathologic complete necrosis rate (the number of patients with >= 95% necrosis divided by the number of evaluable patients) following preoperative treatment with talimogene laherparepvec (T-VEC) in combination with radiation in patients with localized soft tissue sarcoma including a pre-planned interim safety analysis to assess post-surgical wound complications.

SECONDARY OBJECTIVES:

I. To determine the toxicity of talimogene laherparepvec (T-VEC) in combination with radiation in localized soft tissue sarcomas, during neo-adjuvant treatment and post-surgical resection wound complications.

II. To estimate the rate of radiologic response, prior to surgery, and extent of surgical resection.

III. To estimate time to surgery, time to progression, time to recurrence, and death.

TERTIARY OBJECTIVES:

I. To characterize the clinical outcomes within three distinct histologic subtypes: liposarcoma (excluding myxoid liposarcoma), leiomyosarcoma and undifferentiated pleomorphic sarcoma.

II. To characterize the percentage of tumor necrosis in treated tumors. III. To assess if the combination of preoperative talimogene laherparepvec (T-VEC) with radiation will increase the expression of PD-L1 in soft tissue sarcomas.

IV. To assess the impact of preoperative talimogene laherparepvec (T-VEC) with radiation on the tumor infiltrating and circulating immune cells in patients with soft tissue sarcomas.

OUTLINE:

Patients receive talimogene laherparepvec intratumorally (IT) at weeks 1, 4, 6 and 8. Beginning 8-10 days after start of talimogene laherparepvec, patients undergo radiation therapy at weeks 2-6.

After completion of study treatment, patients are followed up at 60 days, every 3 months for 2 years, every 6 months for 1 year, and then every year for up to 5 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Talimogene Laherparepvec (T-VEC) and Radiation in Localized Soft Tissue Sarcoma
Actual Study Start Date : August 15, 2017
Estimated Primary Completion Date : August 1, 2019
Estimated Study Completion Date : August 1, 2019


Arm Intervention/treatment
Experimental: Treatment (talimogene laherparepvec, radiation therapy)
Patients receive talimogene laherparepvec IT at weeks 1, 4, 6 and 8. Beginning 8-10 days after start of talimogene laherparepvec, patients undergo radiation therapy at weeks 2-6.
Other: Laboratory Biomarker Analysis
Correlative studies

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation

Biological: Talimogene Laherparepvec
Given IT
Other Names:
  • ICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene
  • Imlygic
  • JS1 34.5-hGMCSF 47- pA-
  • T-VEC




Primary Outcome Measures :
  1. Pathologic complete response (CR) rate defined as >= 95% of tumor having necrosis [ Time Frame: Up to 5 years ]
    The estimated pathologic CR rate and a 95% confidence interval will be reported.

  2. Incidence of post-surgical wound complications [ Time Frame: Up to 4 months post-surgery ]
    Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.


Secondary Outcome Measures :
  1. Incidence of toxicities of T-VEC in combination with radiation therapy evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ]
    Summary statistics and frequency tables will be used to describe the distributions of the observed adverse events occurring pre-surgery and following surgery. All patients having initiated study treatment will be considered evaluable for toxicity analysis.

  2. Rate of radiologic response evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 5 years ]
    Estimates and confidence intervals will be used to summarize the observed rate of radiologic response.

  3. Rate of surgical response evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 5 years ]
    Estimates and confidence intervals will be used to summarize the observed rate of surgical response.

  4. Time to surgery [ Time Frame: From registration date until surgery, assessed up to 5 years ]
    Will be estimated using Kaplan-Meier methodology.

  5. Time to progression [ Time Frame: From registration date until disease progression, assessed up to 5 years ]
    Will be estimated using Kaplan-Meier methodology.

  6. Time to recurrence [ Time Frame: From registration date until disease recurrence, assessed up to 5 years ]
    Will be estimated using Kaplan-Meier methodology in only those patients having achieved a complete surgical resection.

  7. Time to death [ Time Frame: From registration date until death, assessed up to 5 years ]
    Will be estimated using Kaplan-Meier methodology.


Other Outcome Measures:
  1. Clinical outcomes within liposarcoma, leiomyosarcoma, and undifferentiated pleomorphic sarcoma [ Time Frame: Up to 5 years ]
    Will be assessed.

  2. Percentage of tumor necrosis in treated tumors [ Time Frame: Up to 5 years ]
    Summary statistics and frequency tables will be used to describe tumor necrosis. T-tests, logistic regression, and non-parametric methods, if required, may be used.

  3. Change in PD-L1 expression [ Time Frame: Baseline to time of surgery ]
    Will be evaluated.

  4. Change in tumor infiltrating and circulating immune cells [ Time Frame: Baseline to time of surgery ]
    Will be explored.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Newly diagnosed and histopathologically confirmed (by central pathology review) potentially resectable soft tissue sarcomas of the extremity and trunk of the following subtypes: liposarcoma (excluding myxoid liposarcoma), leiomyosarcoma and undifferentiated pleomorphic sarcoma

    • An incisional or core biopsy is the preferred method for diagnosis; fine needle aspiration is not acceptable
    • Sites permissible for biopsy include

      • Extremities: upper (including shoulder) and lower (including hip)
      • Trunk: body wall
  • Patients must have localized disease with a primary tumor >= 5 cm by magnetic resonance imaging (MRI) or computed tomography (CT) scan
  • Patients must have histologically confirmed grade 2 or 3 tumors by the French Federation of Cancer Centers Sarcoma Group (FNCLCC) sarcoma grading system
  • Patients must have a primary tumor that are determined by multidisciplinary team (medical oncology, orthopedic/surgical oncology, and radiation oncology) to require radiation therapy for optimal management prior to surgical resection
  • Patients must have a sarcoma in the extremity or trunk in location, which is accessible to direct or ultrasound guided injections
  • Karnofsky performance score >= 70
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Absolute lymphocyte count (ALC) >= 800/uL
  • Platelets >= 100,000/uL
  • Hemoglobin >= 9 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN
  • Calculated creatinine clearance > 70 mL/min/1.73 m^2
  • Patient must have a life expectancy of at least 3 months with appropriate therapy
  • Patients must agree to use contraception during study treatment and for 4 months after the end of treatment

    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation, and for four months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to randomization and agree to use effective contraception throughout the treatment period and for 4 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Willingness to provide mandatory tissue and blood samples for correlative studies

Exclusion Criteria:

  • Patients with localized sarcomas that are not of the extremity or trunk wall (including head/neck, retroperitoneum, visceral organs, peritoneum, pelvis within the confines of the bony pelvis, and tumors arising in bone)
  • Patients who have had prior treatment with anti-PD1 or anti-CTLA4 therapy
  • Patients with grade 1 non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) tumors of any size are not eligible
  • Patients with evidence of active bleeding or bleeding diathesis will be excluded (patients with excess of 2.5 mL of hemoptysis are not eligible)
  • Patients requiring therapeutic anticoagulation
  • Patients must have had no prior radiotherapy to tumor-involved sites
  • Patients with gross total resection of the primary tumor prior to enrollment are not eligible; patients who have experienced tumor recurrence after gross total tumor resection are not eligible
  • History of serious or non-healing wound, ulcer, or bone fracture
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1)
  • Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of talimogene laherparepvec (T-VEC) and during the study
  • Previous treatment with talimogene laherparepvec (T-VEC) or any other oncolytic virus
  • Patients with metastatic disease
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to talimogene laherparepvec (T-VEC) or any of its components
  • History or evidence of active autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other); or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) within 2 months of enrollment; (replacement therapy [e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency] is not considered a form of systemic treatment for autoimmune disease)

    • Evidence of clinically significant immunosuppression such as

      • Primary immunodeficiency state such as severe combined immunodeficiency disease
      • Concurrent opportunistic infection
      • Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses > 10 mg/day of prednisone or equivalent within 2 months prior to enrollment
  • Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis)
  • Viral infections requiring intermittent or chronic systemic (intravenous or oral) treatment with an anti-herpetic drug, other than intermittent topical use (e.g., acyclovir)
  • Other viral infections

    • Known to have acute or chronic active hepatitis B or hepatitis C infection
    • Known to have human immunodeficiency virus (HIV) infection
    • Prior therapy with viral-based tumor vaccine
    • Received live vaccine within 28 days prior to enrollment
  • Patients who are unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for herpes simplex virus (HSV)-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec (T-VEC) treatment and through 30 days after the last dose of talimogene laherparepvec (T-VEC)
  • 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 who are pregnant, breastfeeding or plan to become pregnant; sexually active patients and their partners must be willing to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation, and for four months after the last dose of T-VEC

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02923778


Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Steven Robinson Mayo Clinic Cancer Center LAO

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02923778     History of Changes
Other Study ID Numbers: NCI-2016-01461
NCI-2016-01461 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1678
10056 ( Other Identifier: Mayo Clinic Cancer Center LAO )
10056 ( Other Identifier: CTEP )
UM1CA186686 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2016    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Histiocytoma, Malignant Fibrous
Neoplasms, Connective and Soft Tissue
Neoplasms, Muscle Tissue
Neoplasms, Adipose Tissue
Histiocytoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Sarcoma
Leiomyosarcoma
Liposarcoma
Neoplasms by Histologic Type
Neoplasms