Randomized Controlled Trial comparing two groups of Patients with High-Risk, Localized Soft Tissue Sarcoma of the Extremity: the first one receiving Neoadjuvant Pembrolizumab with Radiotherapy and Adjuvant Pembrolizumab after surgery, and the second one receiving Radiotherapy and surgery, aiming to assess the safety and efficacy profile of Pembrolizumab
- Conditions
- This trial investigates whether neoadjuvant radiotherapy combined with pembrolizumab followed by surgical resection and adjuvant pembrolizumab improves disease-free survival for patients with high-risk soft tissue sarcoma of the extremity (undifferentiated pleomorphic sarcoma or dedifferentiated/pleomorphic liposarcoma, tumor size > 5 cm, grade 2 or 3 out of 3) compared to radiotherapy alone followed by surgical resectionMedDRA version: 20.0Level: PTClassification code 10024629Term: Liposarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: HLTClassification code 10041298Term: Soft tissue sarcomas histology unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2018-001360-39-IT
- Lead Sponsor
- SARC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 110
1Age equal to or higher than 12 years
2Histologically confirmed diagnosis of grade 2 or 3 out of 3 UPS or dedifferentiated/pleomorphic LPS of the extremity (including limb girdle, i.e. shoulder or hip) that measures greater than 5 cm in any direction as assessed by imaging; Alternative terms for UPS meeting inclusion criteria include but are not limited to the following
•pleomorphic undifferentiated sarcoma
•unclassified spindle cell sarcoma
•spindle cell sarcoma not otherwise specified
•pleomorphic spindle cell sarcoma
•pleomorphic fibroblastic sarcoma
•undifferentiated high-grade pleomorphic sarcoma
•pleomorphic sarcoma with prominent inflammation
•pleomorphic sarcoma with giant cells
•malignant fibrous histiocytoma (including storiform-pleomorphic and inflammatory subtypes)
•fibrosarcoma
•myxofibrosarcoma (if located deep to the fascia in muscle).
3Patients with non-melanomatous skin cancer, in situ carcinoma, or low-risk prostate cancer can be enrolled.
4 ECOG Performance Status of 0 or 1 (see Appendix A)
5 Resectable primary tumor with no evidence of metastatic disease by imaging. Imaging must be performed within 45 days of Day 1 of study.
6Adequate organ function within 10 days of Day 1 of study defined as:
6.1Absolute Neutrophil Count (ANC) = 1,500/mcL
6.2Platelets = 100,000/mcL
6.3Hemoglobin = 9 g/dL or =5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment)
6.4Serum creatinine < 1.5 X institutional upper limit of normal (ULN) OR measured or calculated creatinine clearance or GFR > 60 mL/min for subject with creatinine level > 1.5 X ULN; Note: Creatinine clearance should be calculated per institutional standard.
6.5ALT (SGOT) and AST (SGPT) = 2.5 X institutional ULN
6.6Serum bilirubin = 1.5 X institutional ULN OR direct bilirubin < ULN for subjects with total bilirubin levels > 1.5 X ULN
6.7Albumin > 2.5 mg/dL
7Written, voluntary informed consent
8 Fertile men and women of childbearing potential must agree to use an effective method of birth control from Day 1 of study and for 120 days after last pembrolizumab administration in both sexes. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test = 72 hours prior to Day 1 of study.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 49
1Prior chemotherapy, targeted small molecule therapy, or radiation therapy for current diagnosis of sarcoma
2Prior radiation therapy in excess of 20 Gy to the site of the current diagnosis of sarcoma. No overlap with prior radiation fields in excess of 20 Gy is allowed.
3Concurrent, clinically significant, active malignancies within two years of study enrollment.
4Patients with locally recurrent sarcoma after surgery alone are eligible for enrollment if other inclusion criteria are met.
5Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
6Major surgery within four weeks prior to Day 1 of study or who have not recovered adequately from prior surgery.
7Currently receiving a study therapy or if they had an investigational agent within 4 weeks at the time of enrollment.
8Women who are pregnant or nursing/breastfeeding, or expecting to conceive or men who are expecting to father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of pembrolizumab.
9Inability to comply with protocol required procedures
10Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy by oral or IV routes within 7 days prior to the first dose of trial treatment
11Known history of active TB (Bacillus Tuberculosis)
12Hypersensitivity to pembrolizumab or any of its excipients
13Metastatic disease or regional lymph node involvement. Chest CT will be mandatory prior to enrollment to evaluate for the presence of metastatic disease. Pulmonary nodule(s) < 5 mm without a histological diagnosis may not be the basis for study exclusion given the lack of specificity of chest CT. If pulmonary nodule(s) measuring 6 – 10 mm are noted on chest CT but appear stable relative to prior chest imaging of at least 6 months duration or if 18FDG-PET scan indicates that the nodule(s) are unlikely to be metastatic disease, then this is permitted. Pulmonary nodules >10 mm should be considered metastatic unless proven otherwise by biopsy/resection or stable appearance for at least 6 months on imaging.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method