Radiation Therapy Before Surgery for Localized, Resectable Soft Tissue Sarcoma of the Extremity and Superficial Trunk

A Phase II Study of Hypofractionated Pre-Operative Radiation Therapy for Localized, Resectable Soft Tissue Sarcoma of the Extremity and Superficial Trunk

This phase II trial investigates the effects of hypofractionated radiation therapy before surgery on wound complications associated with surgery in treating patients with soft tissue sarcoma of the extremity (arms, hands, legs or feet) and superficial trunk that has not spread to other parts of the body (localized) and can be removed by surgery (resectable). Hypofractionated is a shorter radiation therapy treatment length (fewer radiation treatment days) and administers the total radiation dose as larger daily doses, compared to conventionally fractionated therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Stage II Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Resectable Soft Tissue Sarcoma; Stage I Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage IB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Resection; Radiation: Hypofractionated Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To report the major acute wound complication rate associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

SECONDARY OBJECTIVES:

I. To report the 5-year local failure rate associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

II. To report the 5-year disease-free survival rate associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

III. To report the 5-year overall survival rate associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

IV. To report long-term toxicity rates associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

V. To describe patterns of relapse associated with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

VI. To describe patient reported outcomes/quality-of-life outcomes with hypofractionated preoperative radiation therapy, 42.75 Gy in 15 fractions.

OUTLINE:

Patients undergo hypofractionated radiation therapy once daily (QD) (except weekends and holidays) over 3 weeks for a total of 15 fractions. Within 3-6 weeks after completion of radiation therapy, patients undergo surgical resection.

After completion of study treatment, patients are followed up at 4-8 weeks, every 3-4 months for years 1-2, and every 6 months for years 3-5.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed, histological confirmation of soft tissue sarcoma of the extremities (including limb girdle) or superficial trunk that present as either -

  • Deemed a candidate for complete macroscopic resection of the primary sarcoma OR
  • Having had non-oncologic excisional procedure with positive or uncertain resection margins and still be eligible if the evaluating sarcoma surgeon recommends oncologic re-resection of the surgical bed to obtain negative margins after a course of preoperative radiation therapy
• No evidence of nodal or distant metastases as determined by clinical examination on any form of imaging
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 3
• Life expectancy greater than 6 months
• Patients capable of childbearing must use adequate contraception
• Ability to complete questionnaire(s) by themselves or with assistance
• Ability to provide written informed consent
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria:

• Previous radiation therapy to the site of the sarcoma or area surrounding it such that it would be encompassed by the radiation field needed to treat the current sarcoma. In other words, treatment on this trial would require re-irradiation of tissues
• Patients with nodal or distant metastases
• Rhabdomyosarcoma, soft tissue osteosarcoma, soft tissue Ewing sarcoma, and benign histologies

• Any of the following:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception

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: Treatment (hypofractionated radiation therapy, resection); Patients undergo hypofractionated radiation therapy QD (except weekends and holidays) over 3 weeks for a total of 15 fractions. Within 3-6 weeks after completion of radiation therapy, patients undergo surgical resection.

Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Resection; Undergo surgical resection; Other Names: Surgical Resection; Radiation: Hypofractionated Radiation Therapy; Undergo hypofractionated radiation therapy; Other Names: Hypofractionated Radiotherapy; hypofractionation; Radiation, Hypofractionated; Hypofractionated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who experience major wound complications	Will be estimated by the number of patients who experience the major wound complications within 120 days following surgery divided by the total number of evaluable patients. Major wound complication is defined as secondary unplanned operation under general or regional anesthesia for wound repair (e.g.,debridement, operative drainage, or secondary wound closure including rotationplasty, free flaps or skin grafts); or wound management without secondary operation including invasive procedures (e.g., aspiration of seroma or readmission for wound care such as intravenous antibiotics or persistent deep packing for 120 days or longer). 95% confidence intervals using normal approximation to binomial wound complication proportion will be calculated.	Within 120 days of surgical resection of soft tissue sarcoma following preoperative radiation therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local failure rate	Will be defined any radiographic or pathologic evidence of recurrent disease inside the clinical target volume (CTV) and/ or to within 3 cm from the edge of the CTV. Local failure rate at 5 years (LFR5) will be evaluated by the number of patients free of local failure/recurrence at 5 year divided by the total number of evaluable patients. Exact binomial 95% confidence interval for the point estimate will be provided. In the case of censoring prior to 5 years, LFR5 will be estimated using the Kaplan-Meier method.	At 5 years
Disease-free survival	The distribution of disease-free survival will be estimated using method of Kaplan-Meier.	From registration date to the earliest date of documentation of either, local recurrence, regional recurrence, distant recurrence, or death due to any cause, assessed up to 5 years
Overall survival	The distribution of overall survival will be estimated using method of Kaplan-Meier.	From registration date to death due to any cause, assessed up to 5 years
Incidence of late adverse events	The descriptions and grading scales found in the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for adverse event reporting. The rate of >= grade 2 late adverse events will be estimated by the number of patients with a >= grade 2 late adverse event divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true rate of >= grade 2 late adverse events will be calculated.	Between 3 months and 24 months after completion of hypofractionated preoperative radiation therapy
Pattern of relapse	Pattern of relapse will be evaluated by number of patients with patterns of tumor recurrence such as local recurrence, marginal recurrence, regional recurrence, distant metastasis, and second primary tumor divided by the total number of evaluable patients. Exact binomial 95% confidence interval for the point estimate will be provided.	Up to 5 years
Incidence of adverse events	The descriptions and grading scales found in the revised NCI CTCAE version 5.0 will be utilized for adverse event reporting. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.	Up to 5 years
Change in quality of life - PROMIS-10	Results from the ten-item Patient Reported Outcomes Measurement Information System (PROMIS-10) questionnaire will be used to evaluate physical and mental health separately. The Wilcoxon signed-rank test will be utilized to assess changes in raw PROMIS scores. Mean change, along with standard deviation will be reported. The PROMIS-10 consists of ten items that measure physical health, physical functioning, general mental health, emotional distress, satisfaction with social activities and relationships, ability to carry out usual social activities and roles, pain, fatigue and overall quality of life.	Baseline up to 24 months post-surgery
Change in quality of life - TESS	Results from the Toronto Extremity Salvage Score (TESS) questionnaire will be used to evaluate functional outcomes. Mean change from baseline to 24 months post-surgery, along with standard deviation will be reported by version. The TESS was designed as a measure of the difficulty patients have performing routine daily activities. It consists of 31 items with responses from 1 (impossible to do) to 5 (not at all difficult).	Baseline up to 24 months post-surgery

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Safia K. Ahmed, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Estimated): November 15, 2025
• Study Completion (Estimated): November 15, 2026

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: MC1973 (Other Identifier: Mayo Clinic in Rochester); NCI-2020-06811 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 19-011871 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

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