Short Course Of Preoperative Radiotherapy in Head and Neck-, Trunk- and Extremity Soft Tissue Sarcomas (SCOPES)

• ClinicalTrials.gov Identifier: NCT04425967
• Recruitment Status: Recruiting
• First Posted: June 11, 2020
• Last Update Posted: July 24, 2023
• Sponsor: The Netherlands Cancer Institute
• Collaborator: Leiden University Medical Center
• Information provided by (Responsible Party): The Netherlands Cancer Institute

Tracking Information

• First Submitted Date: June 3, 2020
• First Posted Date: June 11, 2020
• Last Update Posted Date: July 24, 2023
• Actual Study Start Date: June 25, 2021
• Estimated Primary Completion Date: April 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2020)

the short-term toxicity [ Time Frame: 30 days post operative ]

wound complications

Original Primary Outcome Measures (submitted: June 9, 2020)

the short-term toxicity of 14 x 3 Gy [ Time Frame: 30 days post operative ]

wound complications

Current Secondary Outcome Measures (submitted: June 9, 2020)

• local control [ Time Frame: 2 years ]
  percentage of patients without local failure after surgery
• long-term toxicity [ Time Frame: 2 years ]
  fibrosis, edema, joint impairment and bone fractures

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Short Course Of Preoperative Radiotherapy in Head and Neck-, Trunk- and Extremity Soft Tissue Sarcomas
• Official Title: Short Course Of Preoperative Radiotherapy in Head and Neck-, Trunk- and Extremity Soft Tissue Sarcomas; a Randomized Phase II Clinical Trial
• Brief Summary: Currently, soft tissue sarcomas (STS) are preoperatively irradiated in a conventionally fractionated regimen of 25 x 2 Gy in five weeks. Recent radiobiological investigations, however, suggest sensitivity to (modest) hypofractionation. Within this study, patients will be randomized to receive either the conventional schedule of 25 x 2 Gy or a shorter preoperative regimen of 14 x 3 Gy, in the hypothesis that both the postoperative wound complication rate until 30 days after surgery, as well as the local control probability at two years are comparable in both arms.

Detailed Description

Surgery is the cornerstone in the treatment of non-metastatic sarcomas. Whenever feasible the resection should include a free surgical margin providing a rim of uninvolved tissue surrounding the tumor. In most deep located tumors however, to preserve essential neurovascular and bone structures and thus to preserve function, the margins are often limited. High grade tumors are, even with wider margins, at higher risk of local failure. Radiotherapy can reduce this risk of local failure.

Preoperative radiotherapy does increase the risk for early complications due to unavoidable irradiation of the normal tissues surrounding the sarcoma mass, particularly for lower extremity lesions (6-9).

Preoperative radiotherapy aims to reduce tumor vitality prior to resection, theoretically allowing more conservative surgical therapy. Postoperative RT allows histological examination of the tumor specimen, especially the margins, aiding in further treatment planning; it may also be associated with fewer early wound complications. (10, 11).

In preoperative radiotherapy, as compared to postoperative radiotherapy, lower doses (50 versus 60 to 66 Gy) and smaller field sizes can be used, resulting in a reduced risk of late, often irreversible, complications. Consequently, preoperative RT is the preferred approach in many centers. Although the outcomes of combined RT and surgery are favorable, approximately 15% of the patients may relapse locally and about 30-50% distantly (dependent upon, among others, age, histopathology, size and grade), stressing the need for further improvement. These improvements should not only be sought in the domain of oncological endpoints, but also in decreasing treatment burden. A reduction in treatment duration, maintaining local control rates without increasing the rates of postoperative wound complications would serve the latter endpoints. For this purpose, quality of life questionnaires as well as patient reported outcomes measurements could come of help.Modern radiobiological investigations suggest that, on average, intermediate to high-grade soft tissue sarcomas may have α/β ratio's substantially below 10 Gy, justifying clinical studies exploring the possibility of (modest) hypofractionation. Obviously, various subtype derived cell lines exhibit different characteristics but on average an α/β ratio of 5 Gy would be a reasonable denominator for sarcomas as a group. However, it is important not to exaggerate hypofractionation in a setting where patients still need to undergo surgery.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

randomization between the standard arm A of 50 Gy in 5 weeks or arm B with hypofractination of 14x3Gy

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Soft Tissue Sarcomas

Intervention

Radiation: pre-operative radiotherapy

pre-operative radiotherapy

Other Name: radiotherapy

Study Arms

• Active Comparator: 25x2Gy
  the conventional schedule of 25 x 2 Gy, once daily fractionation in a five-week OTT
  Intervention: Radiation: pre-operative radiotherapy
• Experimental: 14x3Gy
  the study schedule of 14 x 3 Gy, once daily fractionation in a three-week overall treatment time
  Intervention: Radiation: pre-operative radiotherapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 7, 2020): 163
• Original Estimated Enrollment (submitted: June 9, 2020): 102
• Estimated Study Completion Date: April 1, 2034
• Estimated Primary Completion Date: April 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed newly diagnosed intermediate to high grade soft tissue sarcoma localized to the extremities, trunk and chest wall or the head and neck area, for which the standard treatment is a combination of and radiotherapy and surgery (deep seated and/or > 5cm in largest tumor diameter and/or an anticipated close resection margin and/or grade II/III according to the FNCLCC definition);
• • Absence of regional and/or distant disease. Patients staged by at least a CT scan of the chest (. Staging may also be performed by FDG-PET scanning and or total body MRI scans. Patients with an uncertain metastatic status (e.g. small indifferent lung nodules) and patients with a low metastatic burden not precluding the application of both preoperative radiotherapy and definitive surgery, are allowed to participate;
• WHO Performance Status ≤ 2;
• Able and willing to undergo preoperative radiotherapy;
• Able and willing to undergo definitive surgery;
• Able and willing to comply with regular follow-up visits;

• Able and willing to complete patient reported outcome questionnaires (health-related quality of life and cost effectiveness);

  • Able and willing to undergo randomization;

• Age ≥ 18 years;
• Signed written informed consent

Exclusion Criteria:

• Prior malignancies; except another malignancy and disease-free for ≥ 5 years, or completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma;
• Patients with recurrent sarcomas who underwent prior radiotherapy to the target lesion (if the primary sarcoma was managed by surgery only and no perioperative RT, patients are eligible);
• Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and adult), osteosarcomas;
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
• Female patients who are pregnant;
• Intention to perform an isolated limb perfusion, instead of a tumor resection;
• Neoadjuvant chemotherapy to be scheduled between end of radiotherapy and definitive surgery (neoadjuvant chemotherapy before radiotherapy is allowed);

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Rick Haas, MD, PhD; +31 20 512 9111; r.haas@nki.nl

Contact: Astrid Scholten, MD, PhD; +31 20 512 9111; a.scholten@nki.nl

• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT04425967
• Other Study ID Numbers: M20SCP
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: The Netherlands Cancer Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: The Netherlands Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: Leiden University Medical Center

Investigators

• Principal Investigator: Rick Haas, MD, PhD; The Netherlands Cancer Institute

• PRS Account: The Netherlands Cancer Institute
• Verification Date: July 2023