Blood and Tissue Extraction for Immunological Examinations During Neoadjuvant Therapy of Soft Tissue Sarcomas

"Blood and Tissue Extraction for Immunological Examinations During Neoadjuvant Therapy of Soft Tissue Sarcoma" is a prospective study with additional translational research using preoperative and postoperative tissue, blood sampling and advanced imaging.

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcoma Adult
• Intervention / Treatment: Other: Blood and tissue collection for immunological studies, advanced imaging.; Other: neoadjuvant Therapy

Detailed Description

All patients (> 18 Years) with histologically confirmed high-risk soft tissue sarcoma eligible for neoadjuvant multimodal therapy (including radiotherapy +/- concomitant and sequential chemotherapy +/- hyperthermia as well as surgery) are screened for the study. Neoadjuvant therapy consists of 50-50.4 Gy in 25-28 fractions. Additional concomitant or sequential chemotherapy may be applied in selected cases (young patients, high-grade tumors). Additional hyperthermia concomitant to neoadjuvant radiotherapy is applied in selected cases if not contraindicated.

Preoperative tissue sampling to generate primary tumor cell lines in additional translational research is performed in each patient with a lesion suspect for soft tissue sarcoma and eligible for multimodal therapy. Primary cell lines are analyzed biologically (growth pattern, radioresistance, migration, molecular markers RT-PCR, immunological properties such as immunogenic cell death, lysis by cellular immunotherapies such as CAR-NK cells. Postoperative tumor tissues are additionally analyzed for immune cell mapping using complex immunohistochemistry. Biopsy and resection should include proteome analysis and DNA sequencing (only of the tumor tissue, not normal tissue).

Additional immunological monitoring (including cellular immune status, serum marker e.g. cell free DNA, HMGB1) is performed using blood sampling with in total 4 blood controls (25 ml each, before neoadjuvant radiotherapy, during the second and last week of radiotherapy as well as before surgery). In patients treated with concomitant MR-guided hyperthermia, weekly MR-imagine is performed.

Follow-up is carried out as part of the oncological controls over 5 years. The overall study is planned over a period of 5 years (interventional part), additional 5 years follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Franziska Eckert, MD, Prof.; Phone Number: 82165 +49 7071 29; Email: franziska.eckert@med.uni-tuebingen.de
• Study Contact Backup: Name: Vlatko Potkrajcic, MD; Phone Number: 82165 +49 7071 29; Email: Vlatko.potkrajcic@med.uni-tuebingen.de

Study Locations

• Germany
  • Baden-Württemberg
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Recruiting
      • University Hospital Tuebingen
      • Contact: Vlatko Potkrajcic, MD; Phone Number: 82165 +49 7071 29; Email: Vlatko.potkrajcic@med.uni-tuebingen.de
      • Contact: Cihan Gani, MD; Phone Number: 82165 +49 7071 29; Email: cihan.gani@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Planned histological confirmation for especially high-risk soft tissue sarcoma via open Sampling
• Indication for neoadjuvant multimodal therapy (radiation and locoregional Hyperthermia, optionally with simultaneous chemotherapy)
• Planned resection of a department of the CWS
• Age > 18 years
• Ability to consent
• Additionally for imaging study: Treatment on the combined MR hyperthermia device

Exclusion Criteria:

• Age < 18 years
• Poor understanding (language etc.)
• Lack of reconnaissance ability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single-arm trial; Blood and tissue collection for immunological studies under neoadjuvant Therapy of soft tissue sarcomas. Prospective data collection and translational accompanying research on standard therapy. Use of tissue, blood samples and advanced imaging.	Other: Blood and tissue collection for immunological studies, advanced imaging.; Blood and tissue collection for immunological studies under neoadjuvant Therapy of soft tissue sarcomas. Prospective data collection and translational accompanying research on standard therapy. Use of tissue, blood samples and advanced imaging.; Other: neoadjuvant Therapy; neoadjuvant Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the cellular immune status via flow-cytometrie from collected blood samples	Blood samples are taken on the days of simulation-CT, first and third week of the radiation therapy, as well as before surgery.	5 years of recruitment, 5 years follow-up
Description of the cellular immune status on tissue samples ussing komplex immunohistochemie	Tissue samples are taken as incisional biopsie as well as in the tumor tissue after the surgery	5 years of recruitment, 5 years follow-up
Measurement of the cellular free DNA from collected blood samples	Blood samples are taken on the days of simulation-CT, first and third week of the radiation therapy, as well as before surgery.	5 years of recruitment, 5 years follow-up
Measurement of HMGB1 from collected blood samples	Blood samples are taken on the days of simulation-CT, first and third week of the radiation therapy, as well as before surgery.	5 years of recruitment, 5 years follow-up
Evaluation of morphological tumor characteristics (size, diffusion) with weekly MRIs	Weekly MRIs during neoadjuvant radiation therapy	5 years of recruitment, 5 years follow-up

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Estimated): July 21, 2026
• Study Completion (Estimated): July 21, 2031

Study Registration Dates

• First Submitted: November 23, 2023
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Estimated): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: radiotherapy; neoadjuvant therapy; Soft tissue sarcomas; immunological examinations
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma
• Other Study ID Numbers: 268/2021BO2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No