Clinical trial NCT05109494: Hypofractionated vs Conventional Fractionated RT in Soft Tissue Sarcomas
Official title: Phase II Trial of Neoadjuvant Hypofractionated Radiotherapy Versus Conventionally Fractionated Radiotherapy for Soft Tissue Sarcomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Soft Tissue Sarcoma
Keywords: hypofractionated
radiotherapy
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2021-11-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized by the University of Wisconsin clinical trials team to conventional versus hypofractionated RT. Randomization will be blocked to maintain balance over time, with blocks randomly assigned to sizes of 4 or 6. The randomization will take into account receipt of immunotherapy, to allow for a balance of patients in both arms.
Primary purpose: TREATMENT

Brief summary: This research study is designed to find out if radiation therapy treatment prior to surgery is safe and effective to treat soft tissue sarcomas. 30 participants with soft tissue sarcoma will be enrolled and can expect to be on study for up to 5 years.

Detailed description: Standard treatment for soft tissue sarcomas is a combination of radiation therapy and surgery. Radiation therapy is usually done prior to the surgical removal of the tumor. Most commonly, conventionally fractionated radiotherapy is used for soft tissue sarcomas, in which radiation therapy is given over 25 treatments in a time period of approximately 5 weeks.

Conventionally fractionated radiotherapy is radiation treatment that is delivered over the course of several days; typically divided into doses that are delivered each weekday over a set number of weeks. Each radiation treatment is called a "dose fraction", thus the name "fractionated".

Hypofractionated radiotherapy is a technique in which a higher dose of radiation is given over a fewer number of treatments. Early studies have suggested that hypofractionated radiotherapy will be safe and effective for pre-operative treatment of soft tissue sarcomas. However, because this disease is rare, there are different kinds of soft tissue sarcomas, these tumors can occur anywhere in the body, and conventionally fractionated radiotherapy remains standard, more study is needed to find out if hypofractionated radiotherapy is a safe and effective treatment for this disease.

Therefore, the investigators plan to compare patients treated with conventionally fractionated radiotherapy over 25 treatments in a time period of 5 weeks to patients treated with hypofractionated radiotherapy over 5 treatments in a time period of 1-2 weeks.

The investigators hypothesize hypofractionated radiotherapy in the pre-operative treatment of soft tissue sarcomas can effectively treat soft tissue sarcomas while minimizing side effects and minimizing the time between diagnosis and surgical resection.

Patients with liposarcoma (LPS) or undifferentiated pleomorphic sarcoma (UPS) may receive standard of care pembrolizumab concurrently with radiation therapy at the discretion of their treating medical oncologist.

Primary Objective

* Evaluate soft tissue sarcoma tumor response to neoadjuvant hypofractionated versus conventionally fractionated radiotherapy.

Secondary Objectives

* Evaluate soft tissue sarcoma tumor response to neoadjuvant hypofractionated versus conventionally fractionated radiotherapy.
* Evaluate acute wound healing complications after neoadjuvant hypofractionated versus conventionally fractionated radiotherapy.
* Evaluate late toxicity in patients undergoing neoadjuvant hypofractionated versus conventionally fractionated radiotherapy.
* Evaluate local tumor control and progression-free survival after hypofractionated versus conventionally fractionated radiotherapy.

Exploratory Objectives

* Evaluate surgically resected tissue for markers of tumor cell susceptibility to immune response, immune infiltration, and anti-tumor immune response following neoadjuvant hypofractionated compared to conventionally fractionated radiotherapy
* Evaluate quality of life in patients undergoing neoadjuvant hypofractionated versus conventionally fractionated radiotherapy.

Eligibility criteria: Inclusion Criteria:

* Biopsy proven soft tissue sarcoma of the extremity, trunk, or head and neck
* No prior sarcoma-directed chemotherapy or radiotherapy
* Age ≥ 18 years
* Karnofsky performance status ≥ 60
* Able to understand and sign an informed consent
* Life expectancy of greater than 12 weeks
* Hypofractionated or conventionally fractionated radiotherapy using Intensity Modulated Radiation Therapy (IMRT) are both deemed feasible and safe neoadjuvant treatments, at the treating physician's discretion
* Operable disease and medically fit for surgery, based on the opinion of the consulting surgeon; surgery within 5-14 days of completion of radiation therapy (RT)
* Adequate bone marrow function as defined by absolute neutrophil count \> 500/mcL, hemoglobin \> 8 g/dL, platelets \> 50,000/mcL; adequate renal function as defined by creatinine clearance \> 30 mL/min

Exclusion Criteria:

* Pregnant
* Unable to undergo imaging or positioning necessary for radiotherapy planning

Primary outcomes:
measure: Pathologic Necrosis Score on Surgical Pathology Report
timeFrame: up to 12 weeks from randomization
Secondary outcomes:
measure: Incidence of Surgical Margin Status R0, R1, and R2
timeFrame: up to 12 weeks from randomization
measure: Incidence of acute wound healing complications up to 120 days after surgery
timeFrame: up to 6 months from randomization (up to 120 days after surgery)
measure: Incidence of secondary operation for wound repair
timeFrame: up to 6 months from randomization (up to 120 days after surgery)
measure: Incidence of Late Toxicity
timeFrame: up to 2 years plus or minus 3 months
measure: Progression Free Survival (PFS)
timeFrame: up to 5 years
measure: Rate of Local Tumor Recurrence
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: UW School of Medicine and Public Health
name: Zachary Morris, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: