Preoperative chemotherapy for retroperitoneal sarcoma patients | Anticancerfund

Preoperative chemotherapy for retroperitoneal sarcoma patients

A randomised phase III study of neoadjuvant chemotherapy followed by surgery versus surgery alone for patients with High Risk Retroperitoneal Sarcoma (STRASS 2)  

Status
Recruiting
Cancer types
  • Sarcoma
Trial phase
3

Funding

€700,000.00
ACF donation
€2,894,650.00
EORTC Trial cost

Why this trial?

High grade dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS) originate from the retroperitoneum. Both diseases are characterised by a high risk of spreading and have a dismal prognosis with a risk of death above 70% at 5 years. 

Systemic chemotherapy has the potential to address the risk of cancer spreading, prolong time to relapse and improve overall survival. The neoadjuvant or preoperative setting is preferable for a study in these diseases as it allows to assess drug activity as well as drug effectiveness, study tumour biology and response to therapy, and to immediately address the systemic risk or spreading (which is the leading cause of death in this patient population). Another reason for giving chemotherapy preoperatively is that these patients undergo major abdominal surgery to remove the tumour en bloc, which is associated with a high chance of losing one kidney. It's therefore easier to perform chemotherapy in the preoperative setting, when patients have not yet undergone the procedure above and thus still have optimal kidney function, important for drug clearance. 

The aim of this study is to evaluate whether neoadjuvant chemotherapy reduces the development of distant metastases and increases cure rate in these well-defined histologic entities. It is the first time that a randomised controlled neoadjuvant trial includes only high risk retroperitoneal sarcoma and only two specific histological subtypes.

Why this drug?

Anthracycline-based chemotherapy agents like doxorubicin are the cornerstone of first-line treatment in localised soft tissue sarcoma. Combined with ifosfamide, anthracycline-based chemotherapy is standard of care as preoperative treatment in most sarcoma types. Therefore, this regimen was chosen for high grade LPS patients.  

There is growing retrospective evidence that ifosfamide should be substituted with dacarbazine in the treatment of LMS. Moreover, promising preliminary evidence of efficacy of neoadjuvant anthracycline-ifosfamide chemotherapy in high risk soft tissue sarcoma of the extremities has been published. Therefore, this regimen was chosen for patients with LMS.

Trial design

The EORTC-1809-STBSG STRASS 2 study is an international randomised multicentre open-label phase III trial. In total, 250 patients with high grade DDLPS and LMS will be included (maximum 125 patients per histologic type). Stratification factors are institution and tumour histology. 

Patients will be randomised in two arms:

  • Control arm: large en bloc curative intent surgery approximately 4 weeks after randomisation.
  • Experimental arm: preoperative chemotherapy starting 2 weeks from randomisation, followed by large en bloc curative intent surgery 3-6 weeks after day 1 of the last cycle of chemotherapy.
    • Neoadjuvant chemo for patients with DDLPS: Doxorubicin 75mg/m² (or the equivalent Epirubicin 120mg/m²) + Ifosfamide 9g/m² every 3 weeks.
    • Neoadjuvant chemo for patients with LMS: Doxorubicin 75mg/m² + Dacarbazine 1g/m² every 3 weeks.

Partners

Researchers:  

  • Dr. Alessandro Gronchi, Fondazione IRCCS Instituto Nazionale Dei Tumori, Milan, Italy (Study Chair)
  • Dr. Winan Van Houdt, Netherlands Cancer Institute – Antoni van Leeuwenhoek, Amsterdam, The Netherlands (Study Co-Chair) 

Sponsor: 

  • European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium 

International collaborative groups: 

  • Canadian Cancer Trials Group (CCTG)
  • Australia and New-Zealand Sarcoma Association (ANZSA)
  • Swiss Group for Clinical Cancer Research (SAKK) 

Our role

Financial support
Why we support this trial
Profit is a low priority in cancer treatment for the Anticancer Fund
Intervention has little or no commercial value
The Anticancer Fund wants to maximize the benefit for cancer patients
Expected survival benefit
The Anticancer Fund aims at no major hurdle for clinical implementation
No major hurdle for clinical implementation
The Anticancer Fund supports a trial that benefits a population with high unmet needs
Use in a population with high unmet needs

Funding

€2,894,650.00
EORTC Trial cost
€700,000.00
ACF donation
Questions about participation?
Questions about this trial?
The Anticancer Fund
The Anticancer Fund
studies [at] anticancerfund.org

References

More info: NCT04031677 

https://www.eortc.org/research_field/clinical-detail/1809/

Trans-Atlantic RPS Working Group. Management of Primary Retroperitoneal Sarcoma (RPS) in the Adult: A Consensus Approach From the Trans-Atlantic RPS Working Group. Ann Surg Oncol 2015;22:256–63. doi:10.1245/s10434-014-3965-2. 

Tan MCB, Brennan MF, Kuk D, Agaram NP, Antonescu CR, Qin L-X, et al. Histology-based Classification Predicts Pattern of Recurrence and Improves Risk Stratification in Primary Retroperitoneal Sarcoma. Ann Surg 2016;263:593–600. doi:10.1097/SLA.0000000000001149. 

Gronchi A, Strauss DC, Miceli R, Bonvalot S, Swallow CJ, Hohenberger P, et al. Variabilit y in Patterns of Recurrence After Resection of Primary Retroperitoneal Sarcoma (RPS): A Report on 1007 Patients From the Multi-institutional Collaborative RPS Working Group. Ann Surg 2016;263:1002–9. doi:10.1097/SLA.0000000000001447. 

Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, et al. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol 2017;18:812–22. doi:10.1016/S1470-2045(17)30334-0. 

MacNeill AJ, Gronchi A, Miceli R, Bonvalot S, Swallow CJ, Hohenberger P, et al. Postoperative Morbidity After Radical Resection of Primary Retroperitoneal Sarcoma. Ann Surg 2018;267:959–64. doi:10.1097/SLA.0000000000002250.

Author: Kristine Beckers (Trial Manager) 

Last updated: October 2020