EA7211 – A Randomized Phase III Study of Neoadjuvant Chemotherapy Followed by Surgery versus Surgery Alone for Patients with High Risk Retroperitoneal Sarcoma (STRASS 2)

By Kenneth Cardona, MD

@kencardonaMD

The EA7211 (STRASS 2) trial is a potentially practice-changing study that may redefine global standards of care for patients with high-risk retroperitoneal sarcoma (RPS), a type of soft tissue sarcoma. The current standard of care for these patients is surgical resection, with limited high-level evidence in support of neoadjuvant systemic therapy. Lacking a clear scientific consensus, clinical best practices for RPS can vary significantly between institutions and geographic regions.

EA7211 aims to address this critical knowledge gap. It is the first randomized phase 3 trial to evaluate whether the addition of neoadjuvant chemotherapy, administered prior to standard surgery, improves survival outcomes. Participants will be randomized to receive either three cycles of neoadjuvant chemotherapy (for up to 9 weeks) followed by surgery or surgery alone. The primary endpoint is disease-free survival.

With the recent activation of Addendum #6 (v.06/23/26) to the protocol’s United States Appendix for this international trial, an important change has been made for patient convenience and to ease the burden of participation: Patients randomized to the chemotherapy arm may choose to receive chemotherapy either at the site where they are enrolled in the trial or at an outside location.

• Patients may select one administering site in addition to the enrolling/registering site
• The chemotherapy regimens in this trial are standard-of-care (SOC)
• Care outside the enrollment/registration site extends only to SOC chemotherapy
• The alternative site must be approved by the study investigator at the site where the patient is enrolled and agree to adhere to study requirements as detailed in Section 7 of the parent protocol and Appendix II
  • Note: For visits with study-required assessments, these must be performed by the study investigator at the enrolling/registering site
  • The enrolling/registering site is responsible for notifying the NCI CIRB (via email) that study-specified SOC chemotherapy will be administered at an outside location
• See Appendix II for mandatory agreements, documentation, and adverse event (AE) reporting/compliance requirements

In addition, an important reminder has been added to the SAE reporting requirements:

• Severe adverse events (SAEs) must be reported in both Medidata Rave and in CTEP-AERS within the same timeframe so that the European Organisation for Research and Treatment of Cancer (EORTC) is made aware of them in a timely manner

The trial is open in Europe, Canada, Australia, New Zealand, Japan, and the United States through the ECOG-ACRIN Cancer Research Group. It will enroll a total of 250 patients across these countries. To be eligible for STRASS 2, patients must have high-risk retroperitoneal sarcoma that can be removed by surgery. This includes grade 2 or 3 leiomyosarcoma (LMS) and grade 3 dedifferentiated liposarcoma (DDLPS), with select grade 2 DDLPS cases eligible under specific conditions.

A key innovation of STRASS 2 is its use of histology-tailored chemotherapy regimens, with doxorubicin plus ifosfamide for DDLPS and doxorubicin plus dacarbazine for LMS. The use of tailored chemotherapy reflects a more personalized approach that accounts for the biological differences among soft tissue sarcoma subtypes.

If successful, the study could reshape the standard of care for high-risk retroperitoneal sarcoma by establishing a histology-specific, preoperative chemotherapy strategy that improves disease-free and overall survival in a patient population for whom therapeutic advances have historically been limited.

Please note that this is not a complete list of all updates. For full details, consult the US Appendix and parent protocol (EORTC-1809), posted at CTSU.cancer.gov.

Study resources have been updated to reflect Amendment #6 and are available for download at CTSU.cancer.gov.

Dr. Cardona (Emory University/Winship Cancer Institute) is the study chair for this international trial led in the United States by the ECOG-ACRIN Cancer Research Group, with sponsorship from the National Cancer Institute. Richard Riedel, MD (Duke University/Duke Cancer Institute) is the study co-chair in the US.

Alessandro Gronchi, MD is the study chair in Europe, where the trial sponsor is the European Organisation for Research and Treatment of Cancer (EORTC). Winan Van Houdt, MD, PhD is the study co-chair in Europe.