Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05684874
Other study ID # ET22-301
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date April 21, 2023
Est. completion date January 2024

Study information

Verified date October 2023
Source Centre Leon Berard
Contact Benoît ALLIGNET, MD
Phone +33 4 78 78 59 06
Email benoit.allignet@lyon.unicancer.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This trial is a prospective, monocentric, with minimal risks and constraints study, conducted in patients with Soft Tissue Sarcoma (STS) of the limbs and trunk with indication for neoadjuvant radiotherapy (RT). Patients will be treated by neoadjuvant RT and will have a pre-RT and a post-RT multiparametric quantitative Magnetic Resonance Imaging (MRI). A tumor resection will be performed 6 to 8 weeks post-RT and an anatomopathological observation of the surgical specimen will be performed. This study will allow to describe the initial remnographic characteristics and their evolution after neoadjuvant RT using quantitative multiparametric MRI (mpMRI).


Description:

This study is prospective, monocentric and with minimal risks and constraints. Patients with STS of the limbs and trunk will be accrued during the initial radiotherapy consultation radiotherapy (prior to receiving radiotherapy). Two quantitative multiparametric MRI will be performed. The first one will be acquired less than 14 days before the dosimetric scan, the second one 4 to 6 weeks after the end of the radiotherapy. This study will allow to describe the initial remnographic characteristics and their evolution after neoadjuvant RT using quantitative multiparametric MRI. STATISTICAL ANALYSIS Patients will be systematically recruited from December 2022 to August 2023, i.e. a potential of approximately 20-30 patients. Analysis conventions: Categorical variables will be expressed as numbers and percentages, and continuous variables as median (minimum-maximum). The normality of the distributions of the quantitative MRI data will be assessed by a Shapiro-Wilk test. A p-value <0.05 will be considered significant with two-tailed tests. No imputation will be performed in case of missing data. Statistical analyses will be performed using R software (R Foundation for Statistical Computing, Vienna, Austria). Analysis of the primary endpoint: The remnographic parameters observed pre- and post-radiotherapy will be described, both qualitatively in T1 weighting, T2 with and without fat saturation, T1 with gadolinium injection, and quantitatively in Chemical Shift-Encoded (CSE) MRI sequence, T2 mapping and multi-echo gradient diffusion. Analysis of secondary endpoints: The clinico-remnographic data of the groups with and without complete pathological response will be compared using Student's t test, Wilcoxon test, Chi2 test or Fisher's exact test when appropriate. ROC curves will be generated to assess the performance of the remnographic parameters in predicting pathological complete response as well as in predicting per-treatment progression via the use of the area under the Receiver Operator Characteristic (ROC) curve (AUC). The Youden index will be used to identify the optimal threshold. Univariate and multivariate logistic regressions will be performed to assess the clinico-remnographic parameters predictive of complete pathological response as well as those predictive of per-treatment progression. A Student's t test or a Wilcoxon test will be performed to evaluate the correlation between pre-radiotherapy remnographic parameters and the percentage of variation in tumour volume during treatment, as well as between pre-operative remnographic parameters and the percentage of necrosis on anatomopathological examination of the surgical specimen. DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING Data generated within the framework of the study will be entered, for each patient, by the investigator of the centre (or a person designated by delegation) on an Excel file in a secure location on the internal network of the Centre Léon Bérard. Only New Safety Issues occurring in the course of the study will be reported. A New Safety Issue is defined as any new data that could lead to reevaluate the ratio between the benefits and the risks of the research, or that could be sufficiently important to consider modifications of the research documents, the research management or, to suspend, to interrupt or to modify the protocol of the research or of similar researches. The Sponsor should report without delay any New Safety Issue, as well as any safety measures to be proposed, discussed with the principal investigator, to the Ethics Committee and the principal investigators. Relevant follow-up information will be provided within a further 8 days. The sponsor will assist the investigator in the conduct of the study in accordance with the study protocol, Good Clinical Practice and the regulations in force. At regular intervals during the study, a representative of the coordinating centre may contact the investigating team in order to control the progress of the project, investigator and patient compliance with the protocol and to identify any potential problem in the study.


Recruitment information / eligibility

Status Recruiting
Enrollment 25
Est. completion date January 2024
Est. primary completion date July 5, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility INCLUSION CRITERIA : - Patients 18 years of age or older; - Documented histologic diagnosis of soft tissue sarcoma of the limbs or trunk; - Validated indication for neoadjuvant radiotherapy, planned in the radiotherapy department of the Centre Léon Bérard; - No contraindication to Magnetic Resonance Imaging, - Signed informed consent; - Affiliation with a social security system or beneficiary of such a system. EXCLUSION CRITERIA : - Tumor considered as unresectable or patient considered as non-operable; - Desmoid tumor or dermatofibrosarcoma protuberans due to intermediate malignancy; - Rhabdomyosarcoma due to a different therapeutic management; - Multi-metastatic disease; - Pregnant or lactating woman, - Patient under guardianship, curatorship or deprived of liberty.

Study Design


Intervention

Radiation:
Neoadjuvant RT
Dosimetric CT scan with contrast injection for treatment planning. Radiation therapy at a dose of 50Gy in 25 fractions, 5 fractions per week. Daily pre-treatment positioning tomographic imaging (either high energy (MVCT) or cone beam computed tomography (CBCT)). Delineation of the tumor volume and evaluation of its evolution. In case of change of volume and if medically relevant, new dosimetric scan and collection of the tumor volume.
Other:
Pre-radiotherapy mpMRI
Performed less than 14 days before the dosimetric scan. Conventional morphological T1-weighted, T2-weighted, and T1-weighted imaging sequences after injection of contrast agent. Quantitative imaging sequences including multiple b-value diffusion imaging. Chemical shift sensitized sequences.
Post-radiotherapy mpMRI
Performed 4 to 6 weeks after the end of the radiotherapy. Conventional morphological T1-weighted, T2-weighted, and T1-weighted imaging sequences after injection of contrast agent. Quantitative imaging sequences including multiple b-value diffusion imaging. Chemical shift sensitized sequences.
Procedure:
Tumor resection
Performed 6 to 8 weeks after the end of radiotherapy. An anatomopathological observation of the surgical specimen will be performed.

Locations

Country Name City State
France Centre Léon Bérard Lyon Rhône

Sponsors (1)

Lead Sponsor Collaborator
Centre Leon Berard

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Other Predictive biomarkers of risk factors for tumor progression in pre-radiotherapy mpMRI ROC curves will be generated to evaluate the performance of remnographic parameters for the prediction of per-treatment progression using the area under the ROC curve (AUC). Pre-radiotherapy mpMRI performed within 14 days before the dosimetric scan. 5 weeks of daily image guided radiotherapy.
Other Remnographic data and anatomopathological specimen results Qualitative geographic correlation between post-radiotherapy remnographic data and pathological observation of necrosis, fibrosis and perennial cell areas. 4 to 6 weeks after radiation therapy completion (remnographic data), and 6 to 8 weeks after radiation therapy completion (anatomopathological specimen results).
Primary Maximum axial dimension Evolution of the maximum axial dimension (mm) after neoadjuvant radiotherapy, obtained with quantitative multiparametric MRI Pre-radiotherapy mpMRI performed within 14 days before the dosimetric scan. Post-radiotherapy mpMRI performed 4 to 6 weeks after radiation therapy completion.
Primary Volume of the region of interest (ROI) Evolution of the volume of the region of interest (ROI) (mm3) after neoadjuvant radiotherapy, obtained with quantitative multiparametric MRI Pre-radiotherapy mpMRI performed within 14 days before the dosimetric scan. Post-radiotherapy mpMRI performed 4 to 6 weeks after radiation therapy completion.
Primary Minimum, maximum, mean, median, 10th, 25th, 75th and 90th percentile values of free diffusion (D) and microperfusion-related diffusion (D*). Evolution of the minimum, maximum, mean, median, 10th, 25th, 75th and 90th percentile values of free diffusion (D) and microperfusion-related diffusion (D*) (mm2/s) after neoadjuvant radiotherapy, obtained with quantitative multiparametric MRI Pre-radiotherapy mpMRI performed within 14 days before the dosimetric scan. Post-radiotherapy mpMRI performed 4 to 6 weeks after radiation therapy completion.
Primary Fraction of perfusion (f) Evolution of the fraction of perfusion (f) after neoadjuvant radiotherapy, obtained with quantitative multiparametric MRI Pre-radiotherapy mpMRI performed within 14 days before the dosimetric scan. Post-radiotherapy mpMRI performed 4 to 6 weeks after radiation therapy completion.
Secondary Predictive biomarker of complete pathological response in pre-radiotherapy mpMRI ROC curves will be generated to evaluate the performance of remnographic parameters for the prediction of complete pathological response using the area under the ROC curve (AUC). Pre-radiotherapy mpMRI performed within 14 days before the dosimetric scan. Surgery performed 6 to 8 weeks after radiation therapy completion.
See also
  Status Clinical Trial Phase
Recruiting NCT02910895 - A Platform of Patient Derived Xenografts (PDX) and 2D/3D Cell Cultures of Soft Tissue Sarcomas (STS) N/A
Recruiting NCT05621668 - A First-In-Human Phase 1 Trial of T-Cell Membrane-Anchored Tumor Targeted Il12 (Attil12)- T-Cell Therapy in Subjects With Advanced/Metastatic Soft Tissue and Bone Sarcoma Phase 1
Active, not recruiting NCT04032964 - Dose Finding Study of L19TNF and Doxorubicin in Patients With STS Phase 1
Active, not recruiting NCT04577014 - Retifanlimab (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma Phase 1/Phase 2
Completed NCT01650077 - Therapeutic Response of Patients With Soft Tissue Sarcoma According to CHOI Criteria
Withdrawn NCT04906876 - A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas Phase 2
Terminated NCT02890368 - Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides Phase 1
Terminated NCT02628535 - Safety Study of MGD009 in B7-H3-expressing Tumors Phase 1
Completed NCT02204111 - Patient Directed Intervention to Improve the Quality of Life for Patients With Soft Tissue Sarcoma
Withdrawn NCT01663090 - Ferumoxytol-Enhanced MRI in Adult/Pedi Sarcomas N/A
Completed NCT01440088 - A Trial of TH-302 in Combination With Doxorubicin Versus Doxorubicin Alone to Treat Patients With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma Phase 3
Completed NCT01259375 - Amrubicin Chemotherapy as First Line in Metastatic or Unresectable Soft Tissue Sarcoma Phase 2
Completed NCT01106872 - Bevacizumab, Chemotherapy and Valproic Acid in Advanced Sarcomas Phase 1
Recruiting NCT00753727 - Sunitinib and Radiation in Patients With Resectable Soft-tissue Sarcoma Phase 1/Phase 2
Terminated NCT00755261 - Phase II Study of Doxorubicin and Avastin® in Sarcoma. Phase 2
Completed NCT00611078 - Environmental Pollutants and the Risk of Soft Tissue Sarcoma: A Pilot Study N/A
Completed NCT00580320 - Safety Study of Dacarbazine and Bortezomib in Melanoma and Soft Tissue Sarcoma Phase 1
Completed NCT03452644 - US-Guided Biopsy in the Diagnosis of Musculoskeletal Soft-Tissue Tumors
Recruiting NCT05539677 - Biobank and Register of Patients With Agresive Tumors for Translational and Analytical Research
Terminated NCT03520959 - A Phase 3, Randomized, Double-blind, Placebo-controlled Study For Subjects With Locally-advanced Unresectable or Metastatic Synovial Sarcoma (V943-003, IMDZ-04-1702) Phase 3