Clinical Trials /

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

NCT02923778

Description:

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.

Related Conditions:
  • Leiomyosarcoma
  • Liposarcoma
  • Undifferentiated Pleomorphic Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery
  • Official Title: A Phase 2 Study of Talimogene Laherparepvec (T-VEC) and Radiation in Localized Soft Tissue Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: NCI-2016-01461
  • SECONDARY ID: NCI-2016-01461
  • SECONDARY ID: MC1678
  • SECONDARY ID: 10056
  • SECONDARY ID: 10056
  • SECONDARY ID: UM1CA186686
  • NCT ID: NCT02923778

Conditions

  • 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

Interventions

DrugSynonymsArms
Talimogene LaherparepvecICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene, Imlygic, JS1 34.5-hGMCSF 47- pA-, T-VECTreatment (talimogene laherparepvec, radiation therapy)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVE:

      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.

      CORRELATIVE 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (talimogene laherparepvec, radiation therapy)ExperimentalPatients 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.
  • Talimogene Laherparepvec

Eligibility Criteria

        Inclusion Criteria:

          -  PRE-REGISTRATION ELIGIBILITY CRITERIA:

          -  Because no dosing or adverse event data are currently available on the use of
             talimogene laherparepvec (T-VEC) in patients < 18 years of age, children are excluded
             from this study, but will be eligible for future pediatric trials

          -  Newly diagnosed and a histopathologically potentially resectable soft tissue sarcoma
             of the extremity or trunk of the following subtypes:

               -  Cohort 1: liposarcoma (excluding myxoid liposarcoma)

               -  Cohort 2: leiomyosarcoma

               -  Cohort 3: undifferentiated pleomorphic sarcoma (UPS)/ malignant fibrous
                  histiosarcoma (MFH)

          -  Sites permissible for biopsy include

               -  Extremities: upper (including shoulder) and lower (including hip)

               -  Trunk: Body wall

          -  Patients must have a histologically determined grade 2 or 3 tumor by the FNCLCC
             sarcoma grading system

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  ELIGIBILITY CRITERIA:

          -  Patient has been confirmed (through the protocol specified central review process to
             have newly diagnosed and a histopathologically potentially resectable soft tissue
             sarcoma of the extremity or trunk of the following subtypes:

               -  Cohort 1: liposarcoma (excluding myxoid liposarcoma)

               -  Cohort 2: leiomyosarcoma

               -  Cohort 3: undifferentiated pleomorphic sarcoma (UPS)/malignant fibrous
                  histiosarcoma (MFH)

          -  Patient must have a histologically determined grade 2 or 3 tumor (through the protocol
             specified central review process) by the French Federation of Comprehensive Cancer
             Centers (FNCLCC) sarcoma grading system

          -  Patients must have localized disease with a primary tumor >= 5 cm by magnetic
             resonance imaging (MRI) or computed tomography (CT) scan

          -  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

               -  NOTE: Talimogene laherparepvec (T-VEC), as well as other therapeutic agents used
                  in this trial, may cause fetal harm when administered to a pregnant woman; 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 blood and tissue samples for correlative studies

          -  Willingness to provide a tissue sample that is mandatory at the time of surgery (if
             applicable) and the determination of the primary objective of the study

        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; although no
             effects on embryo-fetal development have been observed in animal studies, adequate and
             well-controlled studies with talimogene laherparepvec (T-VEC) have not been conducted
             in pregnant women; therefore, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response (CR) rate
Time Frame:Up to 5 years
Safety Issue:
Description:Will be defined as >= 95% of tumor having necrosis. The estimated pathologic CR rate and a 95% confidence interval will be reported.

Secondary Outcome Measures

Measure:Incidence of toxicities of T-VEC in combination with radiation therapy
Time Frame:Up to 5 years
Safety Issue:
Description:Will be evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 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.
Measure:Rate of radiologic response
Time Frame:Up to 5 years
Safety Issue:
Description:Will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Estimates and confidence intervals will be used to summarize the observed rate of radiologic response.
Measure:Rate of surgical response
Time Frame:Up to 5 years
Safety Issue:
Description:Will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Estimates and confidence intervals will be used to summarize the observed rate of surgical response.
Measure:Time to surgery
Time Frame:From registration date until surgery, assessed up to 5 years
Safety Issue:
Description:Will be estimated using Kaplan-Meier methodology.
Measure:Time to progression
Time Frame:From registration date until disease progression, assessed up to 5 years
Safety Issue:
Description:Will be estimated using Kaplan-Meier methodology.
Measure:Time to recurrence
Time Frame:From registration date until disease recurrence, assessed up to 5 years
Safety Issue:
Description:Will be estimated using Kaplan-Meier methodology in only those patients having achieved a complete surgical resection.
Measure:Time to death
Time Frame:From registration date until death, assessed up to 5 years
Safety Issue:
Description:Will be estimated using Kaplan-Meier methodology.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

December 9, 2019