This phase I/II trial studies the side effects and best dose of proton-spatially fractionated radiotherapy (P-SFRT) and to see how well it works with standard radiation therapy in treating patients with newly diagnosed retroperitoneal soft tissue sarcoma. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Standard spatially fractionated radiotherapy (SFRT) refers to how the radiation is delivered to the tumor. SFRT means that different parts of the tumor are receiving different doses of radiation (fractionation) through beams that allow areas of higher and lower (peaks and valleys) of doses of the radiation. This spatial fractionation allows an overall high-dose radiation to be given in the peaks and those areas of the tumor may release cells and substances that may help with killing tumor cells, reducing tumor symptoms and shrinking tumors. Proton therapy is a type of radiation therapy that can overcome some of the barriers of standard SFRT. Protons are tiny radioactive particles that can be controlled in a beam to travel up to the tumor and, compared to the particles used in standard radiotherapy, proton therapy can deliver higher doses to the tumor because smaller doses of radiation are delivered to tissues away from the tumor. This allows radiation therapy dose-escalated (continuously increasing the dose of radiation) treatment to tumors even though the tumor is near radiation sensitive organs like the colon. Giving P-SFRT with standard radiation therapy may work better in treating patients with newly diagnosed retroperitoneal soft tissue sarcoma.
Patients must have newly diagnosed, histologically or cytologically confirmed, untreated retroperitoneal soft tissue sarcoma Note: The soft-tissue sarcoma tumor must be at least 3 cm in diameter confirmed by imaging within 30 days of registration
Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
Patients must be age ≥ 18 years on day of signing any informed consent documents
Patients must exhibit a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale or >70% on the Karnofsky Scale
Extra-skeletal Ewing sarcoma
Embryonal rhabdomyosarcoma
Alveolar rhabdomyosarcoma
Desmoplastic small round cell tumor
Sequential
Biopsy
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Intensity-Modulated Radiation Therapy
RadiationUndergo IG-IMRT
Resection
Procedure/SurgeryUndergo surgical resection
Spatially-fractionated Radiation Therapy
RadiationUndergo P-SFRT
Recommended phase II dose (Phase I)
Will be defined as the highest dose with a dose-limiting toxicity (DLTs) as determined in phase I using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0). The DLT will be considered toxic and the prior dose will be considered the MTD (maximum tolerated dose). For the purposes of this protocol, the MTD will be the recommended phase II dose (RP2D).
Pathological complete response (Phase II)
Efficacy will be determined based on pathologic complete response (pCR). A pathologist will score the efficacy and the percentage necrosis which will be based on tissue samples removed during surgery or biopsy after treatment with radiation or chemotherapy.
Incidence of adverse events (Phase I)
Will be summarized by providing a frequency of adverse events (CTCAE v 5.0) by severity, type, timing, and attribution for toxicities of any grade, with rates of ≥ grade 3 toxicities also analyzed separately. Adverse event rates will be summarized and accompanied by 95% exact binomial CIs.
Overall response rate (ORR) (Phase II)
Using imaging, patients who experience an objective response (confirmed complete response \[CR\] or confirmed partial response \[PR\] per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)\].
Progression-free survival (PFS) (Phase II)
Will be assessed by disease progression and is defined as progressive disease (PD) per RECIST v 1.1, other documented clinical or radiographical progression per physician judgment, or death due to disease.
Overall survival (OS) ( (Phase II)
Overall survival will be calculated as the time that elapses between baseline (day of surgery) and the date of death from any cause for all evaluable patients.
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Northwestern University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
