Preoperative vs Postoperative IMRT for Extremity/Truncal STS

• ClinicalTrials.gov Identifier: NCT02565498
• Recruitment Status: Unknown
• First Posted: October 1, 2015
• Last Update Posted: September 11, 2020
• Sponsor: Mount Sinai Hospital, Canada
• Collaborator: Princess Margaret Hospital, Canada
• Information provided by (Responsible Party): Mount Sinai Hospital, Canada

Study Description

Brief Summary:

This study is designed to determine if preoperative image guided radiation therapy (IGRT) delivered using intensity modulated radiation therapy (IMRT) followed by surgery results in similar short-term wound healing complications as surgery followed by postoperative IGRT in patients with extremity or truncal soft tissue sarcoma. Half of the patients will receive preoperative radiotherapy, half will receive postoperative radiotherapy.

Condition or disease	Intervention/treatment	Phase
Adult Soft Tissue Sarcoma	Radiation: Preoperative intensity modulated radiation therapy; Radiation: Postoperative intensity modulated radiation therapy	Phase 3

Detailed Description:

Perioperative RT in addition to surgery is widely accepted as standard management for soft tissue sarcoma (STS) of the extremity and trunk. However, controversy remains as to whether RT should be delivered preoperatively or postoperatively. While both confer similar rates of local control, preoperative RT leads to a decrease in late tissue morbidities such as fibrosis, limb edema, joint stiffness and fracture as compared to postoperative RT. The reasons for this are likely multifactorial, but are in part related to total dose delivered (50 Gray (GY) preoperatively and 60-66 Gy postoperatively) and, based on a previous National Cancer Institute (Canada) Phase III randomized controlled trial, the much larger volume treated in the postoperative setting compared to that in the preoperative setting. The optimal radiation dose used in the postoperative setting is unknown but has been developed empirically and doses of 60-66 Gy are generally employed.However, investigators in Norway/Sweden and France have found equivalent local control rates for patients with negative surgical margins treated with 50 GY postoperativelyThe main concern with preoperative RT has centered on the risk of an increased rate of delayed wound healing and major wound complications. Although some studies suggest it may be possible to reduce the incidence of acute wound healing complications associated with pre-operative radiation than previously seen in the 2D RT era, this has yet to be tested in the phase III setting. IG-IMRT allows a much higher degree of conformality and accurate delivery of dose to the tumour while sparing surrounding normal tissue. This may allow similar rates of acute wound healing complications for pre- and postoperative RT in the treatment of STS.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 206 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Study of Preoperative vs Postoperative Intensity Modulated Radiation Therapy For Truncal/Extremity Soft Tissue Sarcoma
• Study Start Date: June 2016
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Preoperative Radiation Therapy (Arm A); Preoperative intensity modulated radiation therapy followed by surgery	Radiation: Preoperative intensity modulated radiation therapy; 50 Gy delivered in 25 fractions 4-6 weeks prior to surgical excision
Experimental: Postoperative Radiation Therapy (Arm B); Surgery followed by postoperative intensity modulated radiation therapy	Radiation: Postoperative intensity modulated radiation therapy; Surgery followed by 50 Gy delivered in 25 fractions within 6 weeks of surgery for patients with negative margins; for patients with positive margins a boost of 16 Gy in 8 fractions will be added.

Outcome Measures

Primary Outcome Measures :

1. Incidence of acute wound healing complications [ Time Frame: 120 days post surgery ]
   • Secondary operations required for wound treatment (debridement, secondary closure procedures such as rotationplasty, free flaps or skin grafts);
   • Readmission to hospital for wound care;
   • Invasive procedures required for wound care (drainage of hematoma, seroma or infected wound collection);
   • Deep wound packing required at any time (deep packing defined as packing deep to dermis in an area of dehisced wound) to an area of the wound measuring at least 2 cm in length;
   • Prolonged dressing changes, including packing of the wound for greater than six weeks from wound breakdown;
   • Repeat surgery for revision of a split thickness skin graft or requirement for wet dressings for longer than four weeks. (It is permissible for a patient to protect a totally epithelialized skin graft with a dry dressing without declaring a major wound complication)
   • Use of vacuum-assisted closure (VAC)

Secondary Outcome Measures :

1. Acute Radiation Toxicity [ Time Frame: Once per week from the start of radiotherapy until its completion (5 weeks in total), then 1 week preop for Group 1; 4 weeks post completion of treatment for Group 2 ]
   Acute radiation skin toxicity will be documented according to the Radiotherapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria.
2. Late Radiation Toxicity- RTOG Late Radiation Morbidity [ Time Frame: Every 3 months, from 3 months postop for Group 1 and 3 months post RT for Group 2, for 2 years, then 4 monthly for 1 year, then 6 monthly to 5 years. ]
   Late radiation morbidity to skin, subcutaneous tissue, bone and joints will be documented according to the RTOG/EORTC Late Radiation Morbidity Scoring Scheme.
3. Late Radiation Toxicity- Common Toxicity Criteria [ Time Frame: Every 3 months, from 3 months postop for Group 1 and 3 months post RT for Group 2, for 2 years, then 4 monthly for 1 year, then 6 monthly to 5 years. ]
   Late radiation morbidity to skin, subcutaneous tissue, bone and joints will be documented according to the Common Toxicity Criteria v4.0
4. Late Radiation Toxicity- Limb Edema [ Time Frame: Every 3 months, from 3 months postop for Group 1 and 3 months post RT for Group 2, for 2 years, then 4 monthly for 1 year, then 6 monthly to 5 years. ]
   Peripheral limb edema will be documented according to the Late Limb Edema Scoring Criteria.
5. Limb Function [ Time Frame: Within 14 days of randomization, then at 3 and 6 months, 1, 2, 3 and 5 years postop. ]
   Limb function will be documented according to the Musculoskeletal Tumor Society Rating Scale.
6. Patient function [ Time Frame: Within 14 days of randomization, then at 3 and 6 months, 1, 2, 3 and 5 years postop. ]
   Patient function will be documented according to the patient completed Toronto Extremity Salvage Score (TESS)
7. Overall Survival [ Time Frame: Surgery Date until 5 years postoperative or death, whichever occurs first ]
   Overall patient survival in months during the study period
8. Local recurrence-free survival [ Time Frame: Surgery date until 5 years postoperative or local recurrence, whichever occurs first. ]
   Patient survival without a local recurrence in months during the study period.
9. Metastasis-free survival [ Time Frame: Surgery date until 5 years postoperative or systemic recurrence, whichever occurs first. ]
   Patient survival without systemic metastases in months during the study period.

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:

1. Histologically proven soft tissue sarcoma of the extremity or trunk following review by local reference pathologist.
2. Deemed appropriate for preoperative or postoperative radiotherapy and conservative surgery following patient assessment by a radiation oncologist and surgical oncologist.
3. Lesion is primary or locally recurrent. Patient may have undergone excisional biopsy with positive margins at a referring hospital and are eligible following discussion among the surgical oncologists and radiation oncologists that IMRT is an acceptable treatment for that case.
4. Eastern Cooperative Oncology Group (ECOG) score 0-3
5. Patient is aged 18years or older.
6. Patient is able to provide informed consent
7. Patient is available for treatment and follow-up.

Exclusion Criteria:

1. Benign histology.
2. Prior malignancy within the previous five years or concurrent malignancy with the exception of adequately treated basal cell carcinoma of the skin or carcinoma in-situ of the cervix.
3. Prior radiotherapy to the target site
4. Planned chemotherapy for (neo)adjuvant treatment
5. Conservative surgery to the target site
6. Presence of regional nodal disease or unequivocal distant metastases.
7. Other major medical illness deemed to preclude safe administration of protocol treatment or required follow-up.

Contacts and Locations

Contacts

Contact: Anthony Griffin, MSc; (416) 586-5975; anthony.griffin@sinaihealth.ca

Contact: Colleen Dickie, MSc; (416) 946-2000 ext 3467; colleen.dickie@rmp.uhn.on.ca

Locations

United States, Massachusetts

Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Katerina Bubelo 617-582-8340 katerina_bubelo@dfci.harvard.edu

Contact: Patrick Boyle 617-582-8918 pjboyle@dfci.harvard.edu

Principal Investigator: Elizabeth Baldini, MD

United States, Ohio

Cleveland Clinic Taussig Cancer Institute; Recruiting

Cleveland, Ohio, United States, 44195

Contact: Matthew Rerko 216-445-0640 rerkom@ccf.org

Principal Investigator: Chirag Shah, MD

Sub-Investigator: Nathan Mesko, MD

United States, Oregon

Oregon Health & Science University; Recruiting

Portland, Oregon, United States, 97239-3098

Contact: Erh-Ting Hsu, PhD 503-494-5345 hsuer@ohsu.edu

Principal Investigator: Kenneth Gundle, MD

Sub-Investigator: Arthur Hung, MD

Belgium

Cliniques Universitaires Saint-Luc; Recruiting

Brussels, Belgium

Contact: Zeyneb El Mouch +32 2 764 25 60 zeyneb.elmouch@uclouvain.be

Principal Investigator: Thomas Schubert, MD, PhD

Sub-Investigator: Xavier Geets, MD, PhD

Canada, Ontario

The Ottawa Hospital Cancer Centre; Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Contact: Yusra Al Mosuli (613) 737-8920 yalmosuli@ohri.ca

Principal Investigator: Jean-Michel Caudrelier, MD

Sub-Investigator: Joel Werier, MD

Mount Sinai Hospital; Recruiting

Toronto, Ontario, Canada, M5G 1X5

Contact: Anthony Griffin, MSc (416) 586-5975 anthony.griffin@sinaihealth.ca

Principal Investigator: Peter Ferguson, MD

Sub-Investigator: Jay Wunder, MD

Princess Margaret Cancer Centre; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contact: Colleen Dickie, MSc (416) 946-4501 ext 3467 colleen.dickie@rmp.uhn.on.ca

Contact: Anthony M Griffin, MSc 14165865975 anthony.griffin@sinaihealth.ca

Principal Investigator: Peter Chung, MD

Sub-Investigator: Brian O'Sullivan, MD

Sub-Investigator: Charles Catton, MD

Sub-Investigator: David Shultz, MD

Canada, Quebec

Hopital Maisonneuve-Rosemont; Recruiting

Montreal, Quebec, Canada, H1T 2M4

Contact: Hugo St.-Yves, MSc 1-514-252-3400 ext 4428 hstyves.hmr@ssss.gouv.qc.ca

Contact: Janie Barry, MSc 1-514-252-3400 ext 4428 jbarry.hmr@ssss.gouv.qc.ca

Principal Investigator: Nader Khaouam, MD

Sub-Investigator: Sophie Mottard, MD

Sponsors and Collaborators

Mount Sinai Hospital, Canada

Princess Margaret Hospital, Canada

Investigators

• Principal Investigator: Peter Ferguson, MD, FRCSC; MOUNT SINAI HOSPITAL
• Principal Investigator: Peter Chung, MD; Princess Margaret Cancer Centre

More Information

• Responsible Party: Mount Sinai Hospital, Canada
• ClinicalTrials.gov Identifier: NCT02565498
• Other Study ID Numbers: OCREB # 15-070
• First Posted: October 1, 2015
• Last Update Posted: September 11, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Mount Sinai Hospital, Canada:

Soft tissue sarcoma; Extremity; Preoperative radiotherapy; Postoperative radiotherapy

Additional relevant MeSH terms:

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