Pre-operative Hypofractionated Proton Therapy (PRONTO)

PROspective Phase II Trial of Pre-operative Hypofractionated protoN Therapy for Extremity and Truncal Soft Tissue sarcOma

This study is being done to examine whether proton therapy for certain kinds of sarcomas (extremity and trunk soft tissue) is safe and effective. As part of the study, patients will have five fractions of proton therapy before the participants have surgery for the sarcoma. The study will measure wound complications and functional outcomes / quality of life after the procedures.

Patients will be asked to complete questionnaires about the treatment and quality of life from the time of enrollment until about two years after surgery. Otherwise, the participants will have standard of care follow ups with the treatment team.

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Radiation: hypofractionation

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Curtiland Deville, MD; Phone Number: 202-537-4788; Email: cdeville@jhmi.edu
• Study Contact Backup: Name: Ryan Manuel; Email: rmanuel5@jhmi.edu

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20016
      • Recruiting
      • Sibley Memorial Hospital
      • Contact: Curtiland Deville, MD; Phone Number: 202-537-4788; Email: cdeville@jhmi.edu
      • Contact: Dana Kaplin; Phone Number: 410-614-3950; Email: dkaplin1@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (≥18 years of age)
• Patients with primary or locally recurrent extremity or truncal soft tissue sarcoma
• WHO/ECOG status ≤2

Exclusion Criteria:

• History of prior local radiation therapy
• Inability to tolerate treatment position for duration of simulation or treatment
• Tumor originating in retroperitoneal location
• Patients planned for systemic therapy including chemotherapy, targeted agents, and immunotherapy
• Co-existing malignancy or treated malignancy in the last 2 years expected to limit life expectancy; does not include completely resected cutaneous basal cell carcinoma, squamous cell carcinoma, in situ breast or cervical malignancies, or other pathologies at the discretion of the investigators.
• Confirmed pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-operative hypofractionated proton therapy; Patients will have 5 fractions of proton therapy prior to surgical resection of their sarcoma.	Radiation: hypofractionation; This study is being done to see if hypofractionation in treating sarcoma, will also provide patients with a faster and safer treatment outcome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of major wound complications	Number of major wound complications as defined by the CAN-NCIC-SR2 trial ("secondary operation under general or regional anaesthesia for wound repair (debridement, operative drainage, and secondary wound closure including rotationplasty, free flaps, or skin grafts), or wound management without secondary operation…[including] an invasive procedure without general or regional anaesthesia (mainly aspiration of seroma), readmission for wound care such as intravenous antibiotics, or persistent deep packing for 120 days or longer.")	90 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute grade ≥3 adverse events	Rate of acute grade 3 or higher adverse events (CTCAE5)	2 years after treatment
Rate of local recurrence free survival	Number of patients without local recurrence on CT and/or MRI at specified time points.	1 and 2 years after enrollment
Rate of metastasis free survival	Number of patients without metastasis on CT and/or MRI at specified time points.	1 and 2 years after enrollment
Rate of late grade ≥2 radiation toxicity	Rate of grade 2 or higher CTCAE5 adverse events associated with radiation therapy (fibrosis, lymphedema, or joint stiffness).	median two year follow up
Musculoskeletal Tumor Rating Scale scores	The Musculoskeletal Tumor Rating Scale measures physical function in patients with musculoskeletal tumors. The total score for the MSTS ranges 0-30 with higher scores indicating better function.	baseline, 2-12 weeks after end of radiation therapy, after surgery (3-6 month follow up), every 3 months during follow up for 2 years
Toronto Extremity Salvage Score (TESS) scores	The Toronto Extremity Salvage Score (TESS) measures physical function in patients with musculoskeletal tumors. The total score for the TESS ranges 0-100 with higher scores indicating better function.	baseline, 2-12 weeks after end of radiation therapy, after surgery (3-6 month follow up), every 3 months during follow up for 2 years
Functional Assessment of Cancer Therapy-General (FACT-G) scores	The Functional Assessment of Cancer Therapy-General (FACT-G) measures quality of life for patients with cancer. The total score for the FACT-G ranges 0-108 with higher scores indicating better function.	baseline, 2-12 weeks after end of radiation therapy, after surgery (3-6 month follow up), every 3 months during follow up for 2 years
Rate of pathologic complete response	Pathologic complete response rate is reported as the number of patients who achieve pathologic complete response after treatment. As per the NCCN guidelines, pathologic response is graded by the system recommended by the AJCC Cancer Staging Manual and CAP guidelines: Complete response - no remaining viable cancer cells Moderate response - only small clusters/single cancer cells remain Minimal response - residual cancer remaining, but with predominant fibrosis Poor response - minimal/no tumor kills, extensive residual cancer	through study conclusion (estimated 5 years from opening)

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Robert L. Sloan Fund for Cancer Research
• Investigators: Principal Investigator: Curtland Deville, MD, Johns Hopkins School of Medicine

Publications and helpful links

General Publications

• Gogineni E, Chen H, Hu C, Boudadi K, Engle J, Levine A, Deville C Jr. Prospective phase II trial of preoperative hypofractionated proton therapy for extremity and truncal soft tissue sarcoma: the PRONTO study rationale and design. Radiat Oncol. 2024 May 14;19(1):56. doi: 10.1186/s13014-024-02447-0.

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2024
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: June 1, 2023
• First Submitted That Met QC Criteria: June 14, 2023
• First Posted (Actual): June 23, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: soft tissue sarcoma; proton therapy; hypofractionated
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Therapeutics; Radiotherapy; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiation Dose Hypofractionation
• Other Study ID Numbers: SIB2289; IRB00335181 (Other Identifier: Johns Hopkins Medicine)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No