126 Participants Needed

Pembrolizumab + Radiotherapy for Soft Tissue Sarcoma

(SU2C-SARC032 Trial)

Recruiting at 19 trial locations
ST
Overseen BySARC Trials
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: Sarcoma Alliance for Research through Collaboration
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.

What data supports the effectiveness of the drug pembrolizumab for soft tissue sarcoma?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, had a 17.5% response rate in patients with advanced sarcoma, particularly in certain types like undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. This suggests it may help some patients with these specific sarcoma types.12345

Is pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been used in various clinical trials and is generally considered safe for humans, though it can cause side effects like fatigue, cough, nausea, and immune-related issues such as thyroid problems and lung inflammation. It has been approved for use in conditions like melanoma, indicating that its benefits outweigh the risks in certain serious diseases.13456

How is the drug pembrolizumab combined with radiotherapy unique for treating soft tissue sarcoma?

Pembrolizumab is a drug that helps the immune system fight cancer by blocking a protein called PD-1, which can stop the immune system from attacking cancer cells. When combined with radiotherapy, which can also affect the immune system, this treatment may enhance the body's ability to fight soft tissue sarcoma, offering a novel approach compared to traditional chemotherapy.13578

Research Team

DK

David Kirsch, MD, PhD

Principal Investigator

Princess Margaret Cancer Center

Eligibility Criteria

This trial is for people aged 12 or older with high-risk soft tissue sarcoma of the extremity that's larger than 5 cm and hasn't spread. Participants must be in good health, have no other active cancers, not had major surgery recently, and agree to use birth control. Those with autoimmune diseases, infections needing treatment, HIV/Hepatitis B/C, or who are pregnant/nursing can't join.

Inclusion Criteria

My cancer is a specific type and grade, and it's larger than 5 cm.
My cancer has not spread and can be surgically removed.
My organs are functioning well, as tested within the last 10 days.
See 5 more

Exclusion Criteria

I have not received a live vaccine in the last 30 days.
I have had pneumonitis treated with steroids or have it now.
I am currently on medication for an infection.
See 22 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Neoadjuvant pembrolizumab with concurrent radiotherapy followed by surgical resection

Approximately 5 weeks
Multiple visits for radiotherapy sessions

Adjuvant Treatment

Up to fourteen cycles of adjuvant pembrolizumab after surgical resection

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

  • Pembrolizumab
Trial OverviewThe study compares two treatments: one group receives radiotherapy followed by surgery; the other gets a drug called Pembrolizumab with radiotherapy before surgery and continues Pembrolizumab for a year after. It aims to see if adding Pembrolizumab helps more than just radiotherapy and surgery alone.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: TreatmentExperimental Treatment1 Intervention
Neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab.
Group II: Standard of CareActive Control1 Intervention
Neoadjuvant radiotherapy followed by surgical resection.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

🇺🇸
Approved in United States as KEYTRUDA for:
  • Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
  • Melanoma
  • Non-small cell lung cancer (NSCLC)
  • Urothelial carcinoma
  • Colorectal cancer
  • Gastric cancer
  • Hepatocellular carcinoma
  • Renal cell carcinoma
  • Cervical cancer
  • Endometrial carcinoma
🇪🇺
Approved in European Union as KEYTRUDA for:
  • Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
  • Melanoma
  • Non-small cell lung cancer (NSCLC)
  • Urothelial carcinoma
  • Colorectal cancer
  • Gastric cancer
  • Hepatocellular carcinoma
  • Renal cell carcinoma
  • Cervical cancer
  • Endometrial carcinoma
🇬🇧
Approved in United Kingdom as KEYTRUDA for:
  • Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Find a Clinic Near You

Who Is Running the Clinical Trial?

Sarcoma Alliance for Research through Collaboration

Lead Sponsor

Trials
26
Recruited
2,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis profile image

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Stand Up To Cancer

Collaborator

Trials
53
Recruited
40,100+

Findings from Research

In a phase 2 study involving 86 patients with advanced soft-tissue or bone sarcoma, pembrolizumab demonstrated some efficacy, particularly in undifferentiated pleomorphic sarcoma (40% response rate) and dedifferentiated liposarcoma (20% response rate), although the overall response rate did not meet the primary endpoint.
The treatment was associated with some serious adverse events, including immune-related conditions like adrenal insufficiency and pneumonitis, highlighting the need for careful monitoring during therapy.
Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial.Tawbi, HA., Burgess, M., Bolejack, V., et al.[2022]
In a phase II study of pembrolizumab for advanced sarcoma, a 17.5% response rate was observed, particularly in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma, indicating its potential efficacy in these subtypes.
Higher densities of activated T cells and tumor-associated macrophages expressing PD-L1 in pre-treatment biopsies were associated with better responses to pembrolizumab, suggesting that specific immune features may predict treatment outcomes and progression-free survival.
Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab.Keung, EZ., Burgess, M., Salazar, R., et al.[2021]
Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.
Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions.Karim, S., Leighl, N.[2017]

References

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. [2022]
Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. [2021]
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]
Real-world experience with pembrolizumab in patients with advanced soft tissue sarcoma. [2022]
FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]
Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. [2022]
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]