Clinical Research Directory

Study of HS-20093 Versus Gemcitabine in Combination With Docetaxel in Treatment of Osteosarcoma After Previous Second-line Treatment Failure

This is a randomized, controlled, open, multicenter phase III clinical study to evaluate the efficacy and safety of HS-20093 for injection versus gemcitabine in combination with docetaxel in patients with osteosarcoma who have at least second-line treatment failure.

Safety and Efficacy of DIT309 in Advanced Bone and Soft Tissue Sarcomas

This is a open-Label, dose-escalation study to evaluate the safety, tolerability and antitumor activity of DIT309 in subjects with advanced bone and soft tissue sarcomas.The study also plan to explore the Maximum Tolerated Dose (MTD) and determine the Recommended Phase II Dose (RP2D) of the CAR-T cell therapy.

Fight Osteosarcoma Through European Research Evolving Study Platform From Diagnosis to Relapse

This clinical study is the initiative of the FOSTER (Fight OsteoSarcoma Through European Research) consortium and Gustave Roussy, which is the sponsor. Its aim is to evaluate the biology of tumour in greater depth by collecting samples of the tumour during the biopsy at diagnosis, and blood samples. This study is a platform study that evolves over time. This means that it allows for the evaluation of several treatments or therapeutic strategies within a single clinical trial, which can be modified and adapted over time. The FOSTER evolving study platform aim to implement a comprehensive strategy of clinical, biological, radiological, therapeutic integrated research from diagnosis to relapse, with the aim to improve survival of osteosarcoma patients of all age, through randomised therapeutic questions at different phase of treatment from diagnosis to relapse. The platform study makes it possible to evaluate several treatments for the same disease, on an ongoing basis, using a main protocol with adaptable arms. The FOSTER-CabOS trial (part 2 of FOSTER study) is a European Phase III clinical study . It assesses the efficacy of cabozantinib, a tyrosine kinase inhibitor, as a maintenance therapy post-standard treatment in osteosarcoma patients. The trial is randomized against Best Supportive Care to determine the effectiveness of cabozantinib in improving event-free survival. This maintenance therapy aims to prevent relapse among patients who have already received standard treatment for osteosarcoma.

Trastuzumab Deruxtecan (DS-8201a) for the Treatment of Recurrent or Refractory Osteosarcoma, Wilms Tumor, and Desmoplastic Small Round Cell Tumor

This phase I/II trial studies the effects of trastuzumab deruxtecan (DS-8201a) in treating patients with osteosarcoma, Wilms tumor (WT) or desmoplastic small round cell tumor (DSRCT) that is newly diagnosed or has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them.

Agnostic Therapy in Rare Solid Tumors

The ANTARES study is a phase II basket trial designed to evaluate the tissue-agnostic efficacy of the monoclonal anti-PD1 antibody, nivolumab, in patients with advanced or metastatic rare tumors. The study aims to treat rare malignancies with PD-L1 expression (CPS ≥ 10), regardless of the tumor's tissue type or location. Patients who have not responded to standard treatments will be included, and treatment will last for up to 12 months. The study will assess objective response, progression-free survival, and biomarkers such as PD-L1, ctDNA, and microvesicles, in a multicenter collaborative effort to provide innovative therapeutic options for this underrepresented population

EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

This is a phase I, open-label, non-randomized study that will enroll pediatric and young adult research participants with relapsed or refractory non-CNS solid tumors to evaluate the safety, feasibility, and efficacy of administering T cell products derived from the research participant's blood that have been genetically modified to express a EGFR-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express EGFR and the selection-suicide marker EGFRt. EGFRt is a protein incorporated into the cell with our EGFR receptor which is used to identify the modified T cells and can be used as a tag that allows for elimination of the modified T cells if needed. On Arm A of the study, research participants will receive EGFR-specific CAR T cells only. On Arm B of the study, research participants will receive CAR T cells directed at EGFR and CD19, a marker on the surface of B lymphocytes, following the hypothesis that CD19+ B cells serving in their normal role as antigen presenting cells to T cells will promote the expansion and persistence of the CAR T cells. The CD19 receptor harbors a different selection-suicide marker, HERtG. The primary objectives of the study will be to determine the feasibility of manufacturing the cell products, the safety of the T cell product infusion, to determine the maximum tolerated dose of the CAR T cells products, to describe the full toxicity profile of each product, and determine the persistence of the modified cell in the subject's body on each arm. Subjects will receive a single dose of T cells comprised of two different subtypes of T cells (CD4 and CD8 T cells) felt to benefit one another once administered to the research participants for improved potential therapeutic effect. The secondary objectives of this protocol are to study the number of modified cells in the patients and the duration they continue to be at detectable levels. The investigators will also quantitate anti-tumor efficacy on each arm. Subjects who experience significant and potentially life-threatening toxicities (other than clinically manageable toxicities related to T cells working, called cytokine release syndrome) will receive infusions of cetuximab (an antibody commercially available that targets EGFRt) or trastuzumab (an antibody commercially available that targets HER2tG) to assess the ability of the EGFRt on the T cells to be an effective suicide mechanism for the elimination of the transferred T cell products.

A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-E2) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma

The purpose of this study is to see if a new treatment could help patients who have osteosarcoma that does not go away with treatment (is refractory) or comes back after treatment (is recurrent).This study is testing a combination of study therapies, UB-TT170 and genetically modified chimeric antigen receptor T lymphocyte (CAR T) cells, which work together in a way that is different from chemotherapy. In this study, researchers will take some of your blood and remove the T cells in a process called "apheresis". Then the T cells are taken to a lab and changed to CAR T cells that recognize the flags from UB-TT170. Once researchers think they have grown enough CAR T cells, called antiFL(FITC-E2) CAR T cells, to fight your cancer, you may get some chemotherapy to make room in your body for the new cells and then have those cells put back in your body. A few days after the you get your CAR T cell infusion you will start to get infusions of UB-TT170, with the dose slowly increasing for the first few infusions until you have reached a maximum dose that you will get on a regular schedule. The UB-TT170 will attach to your tumor cells and flag them so that they attract the CAR T cells. When the CAR T cells see the labeled tumor cells they can kill the tumor cells. The active part of the study lasts about 8 months, and if you get the CAR T cell infusion you will be in long-term follow-up for 15 years.

Evaluation of the Safety and Efficacy of Mifamurtide Versus Standard Treatment With Sorafenib in Patients With High-risk Osteosarcoma

Prospective, open, interventional, randomized, non-commercial trial

Regorafenib in Patients With Refractory Primary Bone Tumors

The aim of the project is to improve treatment outcomes in patients with primary malignant bone tumors, refractory to standard therapy, by increasing the availability of advanced therapy, as well as to develop treatment options using advanced molecular diagnostics for patients who have not responded to the standard therapeutic regimen, and to introduce modern diagnostics for risk stratification and for the use in molecularly targeted therapies.

Study to Assess Safety and Efficacy of Vactosertib in Adolescents and Adults With Recurrent, Refractory or Progressive Osteosarcoma

MP-VAC-209 is a Phase I/II, open label, single arm, multi-center study to assess safety, tolerability, and antitumor activity of vactosertib as a single agent in adolescents and adults with recurrent, refractory, or progressive osteosarcoma. Vactosertib is given orally, twice a day, to people 12 years of age and older who meet the criteria for study enrollment.

Eflornithine (DFMO) for Ewing Sarcoma and Osteosarcoma

Ewing sarcoma (EWS) and osteosarcoma primarily affect adolescents and young adults. Common treatments include chemotherapy, surgery and radiation, however, there have been few recent advancements in the standard of care. By incorporating eflornithine (DFMO) as an additional therapy and/or maintenance therapy we hope to safely observe improved event-free survival and overall survival. There are 5 cohorts covered under this master protocol.

Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors

The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs for solid tumors. An investigational drug is one that has not been approved by the U.S. Food \& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat. The goals of this part of the study are: * Establish a recommended dose of silmitasertib in combination with chemotherapy * Test the safety and tolerability of silmitasertib in combination with chemotherapy in subjects with cancer * To determine the activity of study treatments chosen based on: * How each subject responds to the study treatment * How long a subject lives without their disease returning/progressing

Dose Escalation Study of CLR 131 in Pediatric Relapsed/Refractory Malignant Tumors Including Neuroblastoma and Sarcomas

The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain tumors for which there are no standard treatment options with curative potential.

Anti-GD2 CAR T Cells in Pediatric Patients Affected by High Risk and/or Relapsed/Refractory Neuroblastoma or Other GD2-positive Solid Tumors

The purpose of this study is to test the safety and efficacy of GD2-CART01, a CAR T cell treatment targeting GD2 in paediatric or young adult patients with High Risk and/or relapsed/refractory Neuroblastoma. A small exploratory cohort of patients with GD2-positive tumors other than Neuroblastoma has also been included.

Atezolizumab in Combination With Stereotactic Body Radiation Therapy (SBRT) and Surgery for Relapsed Osteosarcoma

This study aims to determine the safety and tolerability of combined Atezolizumab, stereotactic body radiation therapy (SBRT), and surgical resection of pulmonary metastases in patients with pulmonary recurrence of osteosarcoma

Olaparib With Ceralasertib in Recurrent Osteosarcoma

This study is being done in order to evaluate the effectiveness of using two drugs (olaparib and ceralasertib) to treat patients with osteosarcoma that has not responded to treatment or has come back after treatment The names of the study drugs involved in this study are: * Olaparib * Ceralasertib

Domatinostat With Sirolimus for Relapsed, Refractory Sarcoma and Osteosarcoma

This is a multicenter, open-label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of domatinostat in combination with sirolimus in adolescents and adults with relapsed or refractory sarcoma and osteosarcoma.

Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas

The purpose of this study is to evaluate the investigational oral drug AMXT 1501 in combination with oral eflornithine (DFMO). An investigational drug is one that has not been approved by the U.S. Food \& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat. The goals of this part of the study are: * Establish a recommended dose of AMXT 1501 in combination with DFMO * Test the safety and tolerability of AMXT 1501 in combination with DFMO * To determine the activity of study treatments chosen based on: * How each subject responds to the study treatment * How long a subject lives without their disease returning/progressing

Cabozantinib With Ifosfamide in Relapsed/Refractory Sarcomas

The purpose of this study is to better understand how safe and effective the drug cabozantinib in combination with high-dose ifosfamide is in the treatment of children and adults with relapsed/refractory sarcomas.

Clinical Orthopaedic Data Bank (Acute and Chronic)

Data involving orthopaedic conditions and rehabilitation aspects of musculoskeletal and neuromuscular disorders will be collected and stored as part of the normal clinical care of patients seen in the University of Florida (UF) and Shands Orthopaedics and Sports Medicine Institute.

Losartan + Sunitinib in Treatment of Osteosarcoma

This study is a Phase 1/1b clinical trial that aims to determine the Maximally Tolerated Dose of Losartan and Sunitinib Combination Therapy. Patients will first be accrued to the Dose Escalation phase of the study, using a 3+3 design. Medication dosages will increase until a maximally tolerated dose is found. Patients will then be accrued to the Dose Expansion phase of the trial, where efficacy of pre-determined dose will be preliminarily assessed.

Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors

This phase II trial studies how well cabozantinib-s-malate works in treating younger patients with sarcomas, Wilms tumor, or other rare tumors that have come back, do not respond to therapy, or are newly diagnosed. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for tumor growth and tumor blood vessel growth.

Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma

This phase III trial compares the effect of open thoracic surgery (thoracotomy) to thoracoscopic surgery (video-assisted thoracoscopic surgery or VATS) in treating patients with osteosarcoma that has spread to the lung (pulmonary metastases). Open thoracic surgery is a type of surgery done through a single larger incision (like a large cut) that goes between the ribs, opens up the chest, and removes the cancer. Thoracoscopy is a type of chest surgery where the doctor makes several small incisions and uses a small camera to help with removing the cancer. This trial is being done evaluate the two different surgery methods for patients with osteosarcoma that has spread to the lung to find out which is better.

Integration of Adaptive Proton Therapy in Pediatric Solid Tumors and Hodgkin's Lymphoma

Pediatric patients receiving proton therapy for solid tumors or Hodgkin's lymphoma may experience anatomical changes during treatment that can affect proton therapy accuracy. This prospective single-arm study uses regular low-dose imaging to monitor these changes and adjust treatment plans as needed. Participants will receive weekly or every-other-week CT scans, with MRI when appropriate, to assess whether the original plan remains accurate. Treatment plans will be updated if tumor coverage decreases by more than 5% or if radiation dose to normal tissues increases by more than 10%; otherwise, the original plan will continue. The study aims to determine how often plan adjustments are needed and to identify which disease sites are most likely to experience significant anatomical changes during treatment. Primary Objective: * Define the frequency of replanning necessary to ensure tumor coverage never falls below 95% (or 5% drop) of the prescribed daily dose in participants with intact (gross) tumors to keep the tumor control optimal throughout the multi-week treatment regimen. * Define the frequency of replanning necessary to ensure organs-at-risk (critical organs) do not deviate by more than 10% of the initially approved dose constraints to keep the normal tissue complication minimal throughout the multi-week treatment regimen. Secondary Objectives * Establish a cone beam CT (CBCT)-based framework for quantifying body surface changes throughout the treatment course. This goal will be achieved by developing a novel algorithm that detects and tracks external anatomical variations longitudinally, without requiring CBCT image enhancement, enabling precise assessment of daily participant setup consistency and anatomical stability. * Overcome daily CBCT quality limitations by generating synthetic CT images that accurately represent daily anatomy and support proton dose recalculation or verification planning. This goal will be achieved by developing a hybrid pipeline that integrates deep learning models with the deformable image registration algorithm, trained and validated on disease site-specific data. This will enable precise dose mapping and tissue density estimation, directly supporting adaptive planning decisions without the need of diagnostic- quality CT images.