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

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)

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)

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 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
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients of child-bearing potential (POCBP) must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) from time of informed consent and for the duration of study participation. Patients who can impregnate their partners must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) from time of informed consent and for the duration of study participation. Should a patient become pregnant or suspect they are pregnant while they or their partner is participating in this study, they should inform their treating physician immediately.
• Note: At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.)
• Note: A POCBP is any person with an egg-producing reproductive tract (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy
• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months)
• POCBP must have a negative urine pregnancy test within 72 hours prior to undergoing CT simulation for P-SFRT. If a urine pregnancy test is positive or cannot be confirmed negative, a serum pregnancy test will be required
• POCBP must be willing and able to use an adequate method of contraception
• Patients with sperm-producing reproductive capacity (PWSPRC) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation, and for 120 days following completion of therapy. PWSPRC treated or enrolled on this protocol must also agree to refrain from donating sperm from time of informed consent for the duration of study participation and for 120 days following completion of therapy
• Patients must have the ability to understand and the willingness to sign a written informed consent document Note: Consent must be obtained within a 30 day period prior to patient registration +7 days.

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 ≤ 14days 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 who have had an allogenic tissue/solid organ transplant
• Patients with a history of inflammatory bowel disorders (i.e., ulcerative colitis, Crohn's disease) or rheumatologic disorders (i.e., Sjogren's, scleroderma, rheumatoid arthritis) that serve as a contraindication to retroperitoneal radiation therapy
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Hypertension that is not controlled on medication

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

• Vinai Gondi, 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, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: July 7, 2026

Record last verified: 2026-07

Locations

US (1)