Clinical Trial - NCT03092323

       

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

Recruiting

Sponsor: Sarcoma Alliance for Research through Collaboration

Collaborators: Stand Up To Cancer, Merck Sharp & Dohme Corp.

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03092323

Protocol Info

Short Description: SU2C-SARC032: Phase II of Neoadj. Pembrolizumab With RT and Adjuvant Pembrolizumab in High-Risk, Localized STS
Long Description: 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
MGH Status: Open
Sponsor: SARC
Disease Program: Sarcoma

Next Steps


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Purpose

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 Title Intervention Phase
Soft Tissue Sarcoma of the Extremity Pembrolizumab Phase 2
Study Type Interventional
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

Primary Outcome Measures

Disease free survival [Time Frame: 2 Years] [Designated as safety issue: ]


Secondary Outcome Measures

Loco-regional disease-free survival [Time Frame: 5 years] [Designated as safety issue: ]

Distant disease free survival [Time Frame: 5 years] [Designated as safety issue: ]

Overall survival [Time Frame: 5 years] [Designated as safety issue: ]

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Time Frame: 5 years] [Designated as safety issue: ]

Estimated Enrollment: 102
Study Start Date: July 2017
Estimated Study Completion Date: July 2025
Estimated Primary Completion Date: July 2024
Arms Assigned Interventions

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.

No Intervention:Standard of Care

Neoadjuvant radiotherapy followed by surgical resection.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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
  • • 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.

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 four weeks 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) 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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03092323

Locations

  • United States, California
    • University of California Los Angeles Los Angeles, California, United States, 90095
  • United States, Florida
    • Mayo Clinic- Florida Jacksonville, Florida, United States, 32224
  • United States, Iowa
    • University of Iowa Hospitals & Clinics Iowa City, Iowa, United States, 52242
  • United States, Maryland
    • Johns Hopkins University Baltimore, Maryland, United States, 21231
  • United States, Massachusetts
    • Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States, 02114
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • University of Michigan Ann Arbor, Michigan, United States, 48109
  • United States, Missouri
    • Washington University Saint Louis, Missouri, United States, 63110
  • United States, New York
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, North Carolina
    • Duke University Durham, North Carolina, United States, 27705
  • United States, Ohio
    • The Ohio State University Columbus, Ohio, United States, 43210
  • United States, Pennsylvania
    • University of Pennsylvania- Abramson Cancer Center Philadelphia, Pennsylvania, United States, 19106
    • University of Pittsburgh (UPMC Hillman Cancer Center) Pittsburgh, Pennsylvania, United States, 15232
  • Australia, New South Wales
    • Chris O'Brien Hospital Camperdown, New South Wales, Australia, 2050
  • Australia, Queensland
    • Princess Alexandra Hospital Brisbane, Queensland, Australia, 4102
  • Australia, Victoria
    • Peter MacCallum Cancer Centre Melbourne, Victoria, Australia, 3000
  • Canada, Quebec
    • McGill University Health Centre Montreal, Quebec, Canada, H4A 3J1
  • Italy, MI
    • Fondazione IRCCS Istituto Nazionale dei Tumori Milano, MI, Italy, 20133

Sponsors and Collaborators

Sarcoma Alliance for Research through Collaboration

Stand Up To Cancer

Merck Sharp & Dohme Corp.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03092323
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

Sarcoma

Pembrolizumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on September 03, 2020