This phase I/II trial tests the safety and effectiveness of ADI-PEG 20 with ifosfamide and mesna in combination with radiation therapy in treating patients with soft tissue sarcoma prior to surgical resection. Although most patients with soft tissue sarcomas present with localized disease (disease that has not spread to other areas in the body), some patients with intermediate- or high-grade sarcoma will develop metastatic disease (disease that has spread from where it first started to other places in the body) despite local tumor control with radiation therapy and surgical resection. Available systemic therapies have limited effectiveness for the majority of sarcoma subtypes and better therapies leading to better local and distant control are needed. ADI-PEG 20 breaks down the amino acid arginine and may block the growth of tumor cells that need arginine to grow. It is a type of iminohydrolase. Chemotherapy drugs, such as ifosfamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Mesna is a chemoprotective agent given with ifosfamide to help protect the bladder from irritation and bleeding. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving ADI-PEG 20 with ifosfamide and mesna in conjunction with radiation therapy may be a safe, tolerable and effective treatment that could lead to improved local and distant control rates of soft tissue sarcomas amenable to surgical resection.

Who can Participate

Inclusion: Patients with pathologically proven diagnosis of grade 2-3 (intermediate or high grade) soft tissue sarcoma of the trunk or extremities with size >= 5 cm that is appropriate for ifosfamide therapy. Patients must be planning to undergo treatment with curative intent Exclusion: Pure well-differentiated liposarcoma, low grade STS, Kaposi sarcoma, bone sarcomas, cartilage sarcomas, or gastrointestinal stromal tumor (GIST) Prior systemic chemotherapy for the study cancer (sarcoma); note that prior chemotherapy for a different cancer is allowable if given greater than three years prior. However, unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (grade 2 or 3 toxicities from prior antitumor therapy that are considered irreversible [defined as having been present and stable for > 6 months] may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by the sponsor-investigator Detailed eligibility criteria is available on ClinicalTrials.gov. These requirements will be discussed with your doctor and/or study representative. ClinicalTrials.gov to learn more about this study.

Study ID

More information available at ClinicalTrials.gov: NCT05813327