Clinical trial NCT02565498: Preoperative vs Postoperative IMRT for Extremity/Truncal STS
Official title: Phase III Study of Preoperative vs Postoperative Intensity Modulated Radiation Therapy For Truncal/Extremity Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Adult Soft Tissue Sarcoma
Keywords: Soft tissue sarcoma
Extremity
Preoperative radiotherapy
Postoperative radiotherapy
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
Collaborators: name: Princess Margaret Hospital, Canada
First posted: 2015-10-01
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Incidence of acute wound healing complications
timeFrame: 120 days post surgery
Secondary outcomes:
measure: Acute Radiation Toxicity
timeFrame: 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
measure: Late Radiation Toxicity- RTOG Late Radiation Morbidity
timeFrame: 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.
measure: Late Radiation Toxicity- Common Toxicity Criteria
timeFrame: 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.
measure: Late Radiation Toxicity- Limb Edema
timeFrame: 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.
measure: Limb Function
timeFrame: Within 14 days of randomization, then at 3 and 6 months, 1, 2, 3 and 5 years postop.
measure: Patient function
timeFrame: Within 14 days of randomization, then at 3 and 6 months, 1, 2, 3 and 5 years postop.
measure: Overall Survival
timeFrame: Surgery Date until 5 years postoperative or death, whichever occurs first
measure: Local recurrence-free survival
timeFrame: Surgery date until 5 years postoperative or local recurrence, whichever occurs first.
measure: Metastasis-free survival
timeFrame: Surgery date until 5 years postoperative or systemic recurrence, whichever occurs first.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Peter Ferguson, MD, FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Cancer Centre
name: Peter Chung, MD
role: PRINCIPAL_INVESTIGATOR
References: