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

• ClinicalTrials.gov Identifier: NCT06385288
• Recruitment Status: Recruiting
• First Posted: April 26, 2024
• Last Update Posted: April 26, 2024
• Sponsor: University Hospital Tuebingen
• Information provided by (Responsible Party): University Hospital Tuebingen

Tracking Information

• First Submitted Date: November 23, 2023
• First Posted Date: April 26, 2024
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: July 21, 2021
• Estimated Primary Completion Date: July 21, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 22, 2024)

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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Blood and Tissue Extraction for Immunological Examinations During Neoadjuvant Therapy of Soft Tissue Sarcomas
• Official Title: Blood and Tissue Extraction for Immunological Examinations During Neoadjuvant Therapy of Soft Tissue Sarcomas
• Brief Summary: "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.

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
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:

Open Label

Primary Purpose: Other

• Condition: Soft Tissue Sarcoma Adult

Intervention

• 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

Study Arms

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.

Interventions:

• Other: Blood and tissue collection for immunological studies, advanced imaging.
• Other: neoadjuvant Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 22, 2024): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 21, 2031
• Estimated Primary Completion Date: July 21, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Franziska Eckert, MD, Prof.; +49 7071 29 ext 82165; franziska.eckert@med.uni-tuebingen.de

Contact: Vlatko Potkrajcic, MD; +49 7071 29 ext 82165; Vlatko.potkrajcic@med.uni-tuebingen.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT06385288
• Other Study ID Numbers: 268/2021BO2
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University Hospital Tuebingen
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital Tuebingen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University Hospital Tuebingen
• Verification Date: July 2023