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

• ClinicalTrials.gov Identifier: NCT04562480
• Recruitment Status: Recruiting
• First Posted: September 24, 2020
• Last Update Posted: December 2, 2021
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mayo Clinic

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
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; Stage II Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8	Radiation: Hypofractionated Radiation Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Resection	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Hypofractionated Pre-Operative Radiation Therapy for Localized, Resectable Soft Tissue Sarcoma of the Extremity and Superficial Trunk
• Actual Study Start Date: November 30, 2020
• Estimated Primary Completion Date: November 15, 2025
• Estimated Study Completion Date: November 15, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients who experience major wound complications [ Time Frame: Within 120 days of surgical resection of soft tissue sarcoma following preoperative radiation therapy ]
   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.

Secondary Outcome Measures :

1. Local failure rate [ Time Frame: At 5 years ]
   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.
2. Disease-free survival [ Time Frame: 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 ]
   The distribution of disease-free survival will be estimated using method of Kaplan-Meier.
3. Overall survival [ Time Frame: From registration date to death due to any cause, assessed up to 5 years ]
   The distribution of overall survival will be estimated using method of Kaplan-Meier.
4. Incidence of late adverse events [ Time Frame: Between 3 months and 24 months after completion of hypofractionated preoperative radiation therapy ]
   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.
5. Pattern of relapse [ Time Frame: Up to 5 years ]
   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.
6. Incidence of adverse events [ Time Frame: Up to 5 years ]
   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.
7. Change in quality of life [ Time Frame: Baseline up to 24 months post-surgery ]
   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.
8. Change in quality of life [ Time Frame: Baseline up to 24 months post-surgery ]
   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 Wilcoxon signed-rank test will be utilized to assess changes in TESS scores within questionnaires.

Eligibility Criteria

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

Criteria

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
• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only. 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

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic in Rochester; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Clinical Trials Referral Office 855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator: Safia K. Ahmed, M.D.

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Safia K Ahmed; Mayo Clinic in Rochester

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04562480
• Other Study ID Numbers: MC1973; NCI-2020-06811 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); MC1973 ( Other Identifier: Mayo Clinic in Rochester ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Posted: September 24, 2020
• Last Update Posted: December 2, 2021
• Last Verified: December 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms