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A Randomized Trial of Pembrolizumab & Radiotherapy Versus Radiotherapy in High-Risk Soft Tissue Sarcoma of the Extremity (SU2C-SARC032)

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ClinicalTrials.gov Identifier: NCT03092323
Recruitment Status : Recruiting
First Posted : March 27, 2017
Last Update Posted : November 9, 2018
Sponsor:
Collaborators:
Stand Up To Cancer
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration

Brief 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. The total duration of pembrolizumab will be one year in the experimental arm.

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma of the Extremity Drug: Pembrolizumab Phase 2

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 19, 2017
Estimated Primary Completion Date : July 1, 2024
Estimated Study Completion Date : July 30, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment
Neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab.
Drug: Pembrolizumab
Pembrolizumab will be administered at 200 mg intravenously every 3 weeks for patients on the treatment arm.
Other Name: KEYTRUDA®

No Intervention: Standard of Care
Neoadjuvant radiotherapy followed by surgical resection.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Loco-regional disease-free survival [ Time Frame: 5 years ]
    The length of time after treatment ends without any locoregional recurrence of sarcoma.

  2. Distant disease free survival [ Time Frame: 5 years ]
    The length of time after treatment ends that the patient survives without any signs or symptoms of sarcoma

  3. Overall survival [ Time Frame: 5 years ]
    The length of time from the start of treatment that patients diagnosed with sarcoma are still alive.



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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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; Alternative terms for UPS meeting inclusion criteria include but are not limited to the following
  • 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. Imaging must be performed within 45 days of Day 1 of study.
  • 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.

Exclusion Criteria:

  • 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 three months prior to Day 1 of study or who have not recovered adequately from prior surgery.
  • 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) > 5 mm are noted on chest CT but appear stable relative to prior chest imaging of at least 6 months duration, then this is permitted.
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03092323


Contacts
Contact: SARC Trials 734-930-7600 SARC@sarctrials.org

Locations
United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
United States, Florida
Mayo Clinic- Florida Recruiting
Jacksonville, Florida, United States, 32224
United States, Iowa
University of Iowa Hospitals & Clinics Recruiting
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27705
Contact: Colleen Piechocki    919-681-1883    colleen.piechocki@duke.edu   
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania- Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19106
University of Pittsburgh (UPMC Hillman Cancer Center) Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Australia, New South Wales
Chris O'Brien Hospital Recruiting
Camperdown, New South Wales, Australia, 2050
Australia, Queensland
Princess Alexandra Hospital Recruiting
Brisbane, Queensland, Australia, 4102
Canada, Quebec
McGill University Health Centre Recruiting
Montreal, Quebec, Canada, H4A 3J1
Sponsors and Collaborators
Sarcoma Alliance for Research through Collaboration
Stand Up To Cancer
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: David Kirsch, MD, PhD Duke University

Responsible Party: Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier: NCT03092323     History of Changes
Other Study ID Numbers: SU2C-SARC032
First Posted: March 27, 2017    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Pembrolizumab
Antineoplastic Agents