Functional Imaging to Identify Radiosensitive Esophageal Cancer - a Biomarker Validation Study (FIRASE)

This trial on biomarker validation investigates the use of innovative re-staging FDG-PET parameters to detect highly chemoradiation (CRT) sensitive squamous cell carcinomas of the esophagus (SCEC) at the end of preoperative or definitive CRT.

Study Overview

• Status: Recruiting
• Conditions: Esophagus Cancer
• Intervention / Treatment: Diagnostic test: Re Staging FDG-PET

Detailed Description

This trial on biomarker validation investigates the use of innovative re-staging FDG-PET parameters to detect highly chemoradiation (CRT) sensitive squamous cell carcinomas of the esophagus (SCEC) at the end of preoperative or definitive CRT. Successful validation of this biomarker could lead to a more individualized approach for patients, i.e. organ preservation in highly chemoradiosensitive patients. Since favorable response to CRT is associated with better outcome of patients, the primary endpoint of the study is an improved event-free-survival (EFS) in responders receiving definitive CRT compared to non-responders. Additional quality of life and other important endpoints (side effects, overall survival, local control, occurrence of distant metastases) will be assessed in both treatment groups.

The investigated PET parameters are Maximum standardized uptake ratio (SURmax) of the primary tumor at week four of chemoradiation and change of maximum standardized uptake value of the non tumor affected esophagus (DeltaNTO).

To improve the treatment in non-responders in future trials, the study has two additional scientific support programmes included: Genetic sequencing of tumor tissue to identify targetable mutations and correlate these with novel imaging biomarkers of none-response on the one hand (biology based treatment optimization). On the other hand the study will include an additional observational study arm. In this arm patients with adenocarcinoma of the esophagus can be included. Our biomarker has only been established in squamous cell carcinomas, therefore it is an interesting exploratory question, if the parameter can also be applied to patients with adenocarcinomas of the esophagus. An additional scientific support program will establish primary tumor cells for better mechanistical understanding of the imaging biomarkers and testing of treatment according to targetable mutations.

• Study Type: Observational
• Enrollment (Estimated): 48

Contacts and Locations

• Study Contact: Name: Sebastian Zschaeck, MD; Phone Number: ++4930450650764; Email: sebastian.zschaeck@charite.de

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité Universitätsmedizin Berlin
    • Contact: Sebastian Zschaeck, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

For the primary endpoint only patients with squamous cell histology will be evaluated. Patients with adenocarcinomas will be used as exploratory cohort.

Description

Inclusion Criteria:

• patients with squamous cell, undifferentiated or adenocarcinoma of the esophagus, UICC stage II-IVA (maximum T4a)
• ECOG performace status 0-2
• Complete clinical staging, including, esophagogastroscopy, EUS, CT neck/thorax/abdomen and adequate pulmonary function.
• Adequate hematological, renal, hepatic and pulmonary functions defined as:

granulocytes ≥ 1.5 x 109/l platelets ≥ 100 x 109/l total bilirubin ≤ 1.5 x upper normal limit creatinine ≤ 120 μmol/L FEV1 ≥ 1.5 L

• Written, voluntary informed consent
• Willingness to perform effective contraceptive practices during treatment for patients with childbearing potential

Exclusion Criteria:

• Evidence of distant metastases (cM1)
• Prior high-dose radiotherapy to the thorax or abdomen
• Primary tumor cT4b
• history or concurrent malignancy as judged by the treating physician. This is only an exclusion criterion if the other malignancy is considered the oncological potentially leading cause of death compared to the esophageal cancer.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	progression free survival is defined as any tumor recurrence (local, regional and or distant) or death	continiously with two year follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	death of patients	continiously with two year follow up
loco-regional recurrence free survival	time without local or regional tumor recurrence	continiously with two year follow up

Collaborators and Investigators

• Sponsor: Sebastian Zschaeck
• Collaborators: Helmholtz Zentrum Dresden Rossendorf, Dresden, Germany
• Investigators: Principal Investigator: Sebastian Zschaeck, MD, Charite University, Berlin, Germany

Publications and helpful links

General Publications

• Zschaeck S, Li Y, Butof R, Lili C, Hua W, Troost ECG, Beck M, Amthauer H, Kaul D, Kotzerke J, Baur ADJ, Ghadjar P, Baumann M, Krause M, Hofheinz F. Combined tumor plus nontumor interim FDG-PET parameters are prognostic for response to chemoradiation in squamous cell esophageal cancer. Int J Cancer. 2020 Sep 1;147(5):1427-1436. doi: 10.1002/ijc.32897. Epub 2020 Feb 19.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2029

Study Registration Dates

• First Submitted: December 19, 2023
• First Submitted That Met QC Criteria: December 19, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: FIRASE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No