Proton-Spatially Fractionated Radiotherapy and Standard Radiation Therapy for the Treatment of Newly Diagnosed Retroperitoneal Soft Tissue Sarcoma

NCT06327477 | Recruiting Phase 1 DMC

• 4 other identifiers: NU 23S01NCI-2024-01927STU00220015P30CA060553
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Retroperitoneal Sarcoma

Outcome Measures

Primary Outcomes (2)

• 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).

  Up to the first 30 days of treatment

• 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.

  Up to 3 years

Secondary Outcomes (4)

• Incidence of adverse events (Phase I)

  Up to 3 years

• Overall response rate (ORR) (Phase II)

  Assessed up to 3 years

• Progression-free survival (PFS) (Phase II)

  Assessed up to 3 years

• Overall survival (OS) ( (Phase II)

  Assessed up to 3 years

Study Arms (1)

Treatment (P-SFRT, IG-IMRT)

EXPERIMENTAL

Patients undergo P-SFRT over 1 fraction and then undergo IG-IMRT over 25-28 fractions for 35 to 42 days. Patients undergo surgical resection 21 to 35 days after radiation therapy. Patients undergo blood sample collection during screening and on study. Patients also undergo biopsy during screening and CT on study and on follow up.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Resection; Radiation: Spatially-fractionated Radiation Therapy

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (P-SFRT, IG-IMRT)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (P-SFRT, IG-IMRT)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (P-SFRT, IG-IMRT)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IG-IMRT

Also known as: IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Treatment (P-SFRT, IG-IMRT)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Treatment (P-SFRT, IG-IMRT)

Spatially-fractionated Radiation Therapy RADIATION

Undergo P-SFRT

Also known as: GRID Therapy, SFRT

Treatment (P-SFRT, IG-IMRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have newly diagnosed, histologically or cytologically confirmed, untreated retroperitoneal soft tissue sarcoma
• The soft-tissue sarcoma tumor must be at least 3 cm in diameter
• 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
• Leukocytes (white blood cells \[WBC\]) ≥ 3,000/mcL
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Note: growth factor/transfusion is not permitted prior to these measurements being taken
• Hemoglobin (Hgb) ≥ 9 g/d
• Platelets (PLT) ≥ 100,000/mcL
• Total bilirubin \< 1.5 x upper limit of normal (ULN) (or direct bilirubin \< ULN)
• Aspartate Transferase (AST) ( serum glutamic-oxaloacetic transaminase \[SGOT\]) ≤ 2.5 x institutional ULN
• Alanine transaminase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 2.5 x institutional ULN
• Creatinine ≤ 1.5 x upper limit of normal (ULN)
• Creatinine clearance ≥ 50mL/min

You may not qualify if:

• Patients who have had one of the following soft tissue sarcoma subtypes where neoadjuvant chemotherapy is established as standard-of-care:
• Extra-skeletal Ewing sarcoma
• Embryonal rhabdomyosarcoma
• Alveolar rhabdomyosarcoma
• Desmoplastic small round cell tumor
• Patients who have had any prior radiation therapy to the affected area
• Patients who have had chemotherapy, radiotherapy, or other antineoplastic agents ≤ 28 days (6 weeks for nitrosureas or mitomycin C) prior to planned treatment start date
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
• Patients who have taken steroid therapy or any other immunosuppressive therapy within 7 days of first dose prior to trial treatment
• Patients with a known history of active tuberculosis (TB) (Bacillus tuberculosis)
• Patients with a known history of active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected) infection
• Patients with current or a history of any distant metastatic disease (including brain). Note: an isolated or oligo-metastatic regional occurrence may be allowed if all other criteria have been met and curative attempt is being pursued
• Patients with a known history of (non-infectious) pneumonitis that required steroids or had evidence of current pneumonitis
• Patients who have received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally killed virus vaccines, and as such, patients who have received these vaccines are not excluded; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed
• Patients who have had an allogenic tissue/solid organ transplant

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Interventions

Biopsy; Specimen Handling; Radiotherapy, Intensity-Modulated

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Seth M Pollack, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

3126951301; cancer@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 25, 2024
• Study Start: April 2, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: October 20, 2025

Record last verified: 2025-10

Locations

US (1)