Soft Tissue Sarcoma of the ExtremityPhase 2SU2C-SARC032NCT03092323
A Randomized Trial of Pembrolizumab & Radiotherapy Versus Radiotherapy in High-Risk Soft Tissue Sarcoma of the Extremity
A Phase 2 study testing Pembrolizumab in people with Soft Tissue Sarcoma of the Extremity, run by Sarcoma Alliance for Research through Collaboration at 20 sites in 4 countries.
Trial summary
This is an open-label, multi-institutional phase II randomized study comparing neoadjuvant radiotherapy followed by surgical resection to neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Soft Tissue Sarcoma of the Extremity
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 20 sitesin 4 countries
- Study dates
- 19 Jul 2017to 1 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥ 12 years
- Histologically 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
- Patients with non-melanomatous skin cancer, in situ carcinoma, or low-risk prostate cancer can be enrolled.
- ECOG Performance Status of 0 or 1
- Resectable primary tumor with no evidence of metastatic disease by imaging.
- Adequate organ function within 10 days of Day 1
- Written, voluntary informed consent
- 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.
Who cannot join
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy for current diagnosis of sarcoma
- Prior 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.
- Concurrent, clinically significant, active malignancies within two years of study enrollment.
- Patients with locally recurrent sarcoma after surgery alone are eligible for enrollment if other inclusion criteria are met.
- Patients 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
- Major surgery within four weeks prior to Day 1 of study or who have not recovered adequately from prior surgery.
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- Currently receiving a study therapy or if they had an investigational agent within 4 weeks at the time of enrollment.
- Women 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.
- Inability to comply with protocol required procedures
- Diagnosis 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
- Known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients
- Metastatic 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.
- Unresectable disease or medically inoperable
- Planned to receive neoadjuvant or adjuvant chemotherapy for current diagnosis of localized soft tissue sarcoma
- Active autoimmune disease that has required systemic treatment in the past two years (i.e. with use of disease modifying agents, systemic corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis.
- Active infection requiring systemic therapy
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Known active Hepatitis B (e.g., HBsAg reactive, confirmed by detectable viral load) or Hepatitis C (e.g., HCV RNA [qualitative] detected)
- Received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Diagnosis of scleroderma.
- Diagnosis of inflammatory bowel disease (Crohn's disease or Ulcerative Colitis).
Trial locations and contacts
20 sites in 4 countries.
20 sites in 4 countries
United States15 sites
University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins University
Baltimore, Maryland, 21231
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
The Ohio State University
Columbus, Ohio, 43210
Duke University
Durham, North Carolina, 27705
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Mayo Clinic- Florida
Jacksonville, Florida, 32224
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of California Los Angeles
Los Angeles, California, 90095
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Pennsylvania- Abramson Cancer Center
Philadelphia, Pennsylvania, 19106
University of Pittsburgh (UPMC Hillman Cancer Center)
Pittsburgh, Pennsylvania, 15232
Oregon Health & Science University
Portland, Oregon, 97239
Washington University
St Louis, Missouri, 63110
Australia3 sites
Princess Alexandra Hospital
Brisbane, Queensland, 4102
Chris O'Brien Hospital
Camperdown, New South Wales, 2050
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
About this study
Official title: SU2C-SARC032: A Phase II Randomized Controlled Trial of Neoadjuvant Pembrolizumab With Radiotherapy and Adjuvant Pembrolizumab in Patients With High-Risk, Localized Soft Tissue Sarcoma of the Extremity
This is an open-label, multi-institutional phase II randomized study comparing neoadjuvant radiotherapy followed by surgical resection to neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab. The total duration of pembrolizumab will be one year in the experimental arm.
Read the detailed description
This is a multicenter, randomized phase II trial with an initial safety run-in to test the safety and efficacy of neoadjuvant pembrolizumab with image-guided radiotherapy and adjuvant pembrolizumab compared to radiation therapy alone in patients with clinically localized extremity soft tissue sarcoma at high risk for developing metastatic disease (tumor size > 5 cm, intermediate- to high-grade; approximately 50% risk for distant disease at 2 years). Histologies will be limited to undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma based on preliminary data from SARC028. Other terms for undifferentiated pleomorphic sarcoma may include, but are not limited to. 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, pleomorphicsarcoma with prominent inflammation, pleomorphic sarcoma with giant cells, malignant fibrous histiocytoma (including storiform-pleomorphic and inflammatory subtypes), fibrosarcoma, and myxofibrosarcoma (located deep to the fascia in muscle). Radiation therapy with three cycles of pembrolizumab will be administered as neoadjuvant therapy for patients randomized to the experimental arm. These patients will also receive up to fourteen cycles of adjuvant pembrolizumab after surgical resection. Patients in the standard of care arm will receive neoadjuvant radiotherapy (50 Gy in 25 fractions) followed by surgical resection as in RTOG 0630.
- Conditions
- Soft Tissue Sarcoma of the Extremity
- Being tested
- Pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called KEYTRUDA®
Pembrolizumab will be administered at 200 mg intravenously every 3 weeks for patients on the treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab. Receives: Drug: Pembrolizumab |
| Standard of Care | No intervention | Neoadjuvant radiotherapy followed by surgical resection. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival
Disease recurrence is defined as clinically diagnosed or biopsy-confirmed recurrent sarcoma at a site distant to the primary tumor, including nodal metastasis, loco-regional recurrence, and death without documented recurrence.
Measured: 2 Years
Secondary outcomes (4)
Loco-regional disease-free survival
The length of time after treatment ends without any locoregional recurrence of sarcoma.
Measured: 5 years
Distant disease free survival
The length of time after treatment ends that the patient survives without any signs or symptoms of sarcoma
Measured: 5 years
Overall survival
The length of time from the start of treatment that patients diagnosed with sarcoma are still alive.
Measured: 5 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Test the safety of neoadjuvant pembrolizumab administered with conventionally fractionated radiotherapy targeting soft tissue sarcoma of the extremity.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start19 Jul 2017
- Primary completion1 Sep 2025 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Soft Tissue Sarcoma of the ExtremityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sarcoma Alliance for Research through Collaboration
- Sponsor type
- University, hospital or other
- Collaborators
- Stand Up To Cancer, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- David Kirsch, MD, PhD, Principal investigator, Princess Margaret Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03092323
- Sponsor's protocol ID
- SU2C-SARC032
- Acronym
- SU2C-SARC032
- Status last verified
- May 2023
- First submitted
- 15 Mar 2017
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mowery YM, Ballman KV, Hong AM, Schuetze SM, Wagner AJ, Monga V, Heise RS, Attia S, Choy E, Burgess MA, Bae S, Pryor DI, Van Tine BA, Tinoco G, Chmielowski B, Freeman C, Gronchi A, Meyer CF, Dickson MA, Hartner L, Davis LE, Powers BC, Moding EJ, Weinhold KJ, van de Rijn M, Brigman BE, Riedel RF, Kirsch DG. Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial. Lancet. 2024 Nov 23;404(10467):2053-2064. doi: 10.1016/S0140-6736(24)01812-9. Epub 2024 Nov 12.
PubMed 39547252
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SU2C-SARC032: A Phase II Randomized Controlled Trial of Neoadjuvant Pembrolizumab With Radiotherapy and Adjuvant Pembrolizumab in Patients With High-Risk, Localized Soft Tissue Sarcoma of the Extremity
- ClinicalTrials.gov ID
- NCT03092323
- Acronym / sponsor ID
- SU2C-SARC032 / SU2C-SARC032
- Conditions
- Soft Tissue Sarcoma of the Extremity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- Sarcoma Alliance for Research through CollaborationUniversity, hospital or other
- Collaborators
- Stand Up To Cancer, Merck Sharp & Dohme LLC
- Study start
- 19 Jul 2017 (actual)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 27 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multi-institutional phase II randomized study comparing neoadjuvant radiotherapy followed by surgical resection to neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab. The total duration of pembrolizumab will be one year in the experimental arm.
Detailed description
This is a multicenter, randomized phase II trial with an initial safety run-in to test the safety and efficacy of neoadjuvant pembrolizumab with image-guided radiotherapy and adjuvant pembrolizumab compared to radiation therapy alone in patients with clinically localized extremity soft tissue sarcoma at high risk for developing metastatic disease (tumor size > 5 cm, intermediate- to high-grade; approximately 50% risk for distant disease at 2 years). Histologies will be limited to undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma based on preliminary data from SARC028. Other terms for undifferentiated pleomorphic sarcoma may include, but are not limited to. 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, pleomorphicsarcoma with prominent inflammation, pleomorphic sarcoma with giant cells, malignant fibrous histiocytoma (including storiform-pleomorphic and inflammatory subtypes), fibrosarcoma, and myxofibrosarcoma (located deep to the fascia in muscle). Radiation therapy with three cycles of pembrolizumab will be administered as neoadjuvant therapy for patients randomized to the experimental arm. These patients will also receive up to fourteen cycles of adjuvant pembrolizumab after surgical resection. Patients in the standard of care arm will receive neoadjuvant radiotherapy (50 Gy in 25 fractions) followed by surgical resection as in RTOG 0630.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: PembrolizumabNeoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab. |
| Standard of Care | No intervention | –Neoadjuvant radiotherapy followed by surgical resection. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 12 years
- Histologically 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
- Patients with non-melanomatous skin cancer, in situ carcinoma, or low-risk prostate cancer can be enrolled.
- ECOG Performance Status of 0 or 1
- Resectable primary tumor with no evidence of metastatic disease by imaging.
Key exclusion criteria (25 listed)
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy for current diagnosis of sarcoma
- Prior 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.
- Concurrent, clinically significant, active malignancies within two years of study enrollment.
- Patients with locally recurrent sarcoma after surgery alone are eligible for enrollment if other inclusion criteria are met.
- Patients 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KEYTRUDA®Pembrolizumab will be administered at 200 mg intravenously every 3 weeks for patients on the treatment arm. | Drug | Treatment |
Primary outcome
Disease free survival
Time frame: 2 Years
Disease recurrence is defined as clinically diagnosed or biopsy-confirmed recurrent sarcoma at a site distant to the primary tumor, including nodal metastasis, loco-regional recurrence, and death without documented recurrence.
4 secondary outcomes
Loco-regional disease-free survival
Time frame: 5 years
Distant disease free survival
Time frame: 5 years
Overall survival
Time frame: 5 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Derived from this study: PubMed 39547252Mowery YM, Ballman KV, Hong AM, Schuetze SM, Wagner AJ, Monga V, Heise RS, Attia S, Choy E, Burgess MA, Bae S, Pryor DI, Van Tine BA, Tinoco G, Chmielowski B, Freeman C, Gronchi A, Meyer CF, Dickson MA, Hartner L, Davis LE, Powers BC, Moding EJ, Weinhold KJ, van de Rijn M, Brigman BE, Riedel RF, Kirsch DG. Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial. Lancet. 2024 Nov 23;404(10467):2053-2064. doi: 10.1016/S0140-6736(24)01812-9. Epub 2024 Nov 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Kirsch, MD, PhD principal investigator
Princess Margaret Cancer Center
20 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Soft Tissue Sarcoma of the Extremity, run by Sarcoma Alliance for Research through Collaboration at 20 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Australia, Canada, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease free survival (time frame: 2 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03092323, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.