Status and phase
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About
The proposed study is designed to treat locally advanced soft tissue sarcoma (STS) subtypes with neoadjuvant talimogene laherparepvec (TVEC) and preoperative external beam radiation therapy (EBRT).
Full 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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Subject has provided informed consent.
Histologically confirmed diagnosis of locally advanced STS subtypes (including undifferentiated pleomorphic sarcoma, myxofibrosarcoma, and malignant peripheral nerve sheath tumor (MPNST)) that are unresectable with clear wide margins, for which preoperative radiotherapy is considered appropriate.
EXAMPLES:
Previous treatment: prior systemic anti-cancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy are allowed provided therapy completed at least1 year prior to enrollment.
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).
5.2 Eligibility Exclusion Criteria
Sarcoma histologies that are not consistent with undifferentiated pleomorphic sarcoma, myxofibrosarcoma, or MPNST
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 uncontrolled gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn's disease) or other symptomatic uncontrolled autoimmune disease including, inflammatory bowel disease, or history of any poorly controlled or severe systemic autoimmune disease (i.e., severe rheumatoid arthritis requiring biologic treatment, systemic lupus erythematosus, scleroderma, 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 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. Patients on therapeutic low molecular weight heparin may be allowed provided the dose can be safely held as per the treating investigator on the morning of scheduled intratumoral injection and can be resumed 12 hours after the procedure.
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 -
Evidence of hepatitis C - a)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 8.5 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.
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:
Primary purpose
Allocation
Interventional model
Masking
2 participants in 1 patient group
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Central trial contact
John Rieth, MD
Data sourced from clinicaltrials.gov
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