Clinical Research Directory

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.

Preoperative Immunonutrition in Patients With Bone and Soft Tissue Sarcomas

This study will evaluate whether a short nutritional intervention before surgery can improve recovery in patients with bone and soft tissue sarcomas. Patients with these tumors often have a higher risk of poor nutrition and loss of muscle mass. These problems may increase the risk of complications after major orthopedic surgery. Participants will be randomly assigned to one of two groups. One group will receive a special oral nutritional supplement twice daily before surgery, in addition to standard care. The other group will receive standard care without the preoperative nutritional supplement. The main aim of the study is to compare the rate of clinically relevant postoperative complications within 30 days after surgery. The study will also evaluate changes in muscle mass on CT scans, blood markers of nutrition and inflammation, nutritional risk, functional status, length of hospital stay, and tolerance of the nutritional supplement.

Novel RNA-lipid Particle (RNA-LP) Vaccine for Anti-PD-1 Antibody Therapy Sensitization

The goal of this phase I trial is to evaluate the toxicity and feasibility of a tumor-specific RNA-NP vaccine in patients with stage IIB-IV melanoma who have evidence of progressive disease by RECIST 1.1 criteria while receiving adjuvant aPD1 therapy, or those who progress within 6 months of completion of adjuvant treatment, or unresectable stage II soft tissue sarcoma or stage III-IV soft tissue sarcoma.

LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas

This phase II trial studies how well autologous tumor infiltrating lymphocytes LN-145 (LN-145) or LN-145-S1 works in treating patients with ovarian cancer, triple negative breast cancer (TNBC), anaplastic thyroid cancer, osteosarcoma, or other bone and soft tissue sarcomas that do not respond to treatment (refractory) or that has come back (relapsed). LN-145 is made by collecting and growing specialized white blood cells (called T-cells) that are collected from the patient's tumor. LN-145-S1 is made using a modified process that chooses a specific portion of the T-cells. The T cells may specifically recognize, target, and kill the tumor cells.

Gemcitabine Plus Ascorbate for Sarcoma in Adults (Pilot)

This study will enroll patients who have a diagnosis of locally advanced, unresectable or metastatic soft tissue or bone sarcoma (except gastrointestinal stromal tumors and Kaposi's sarcoma) from any site.

Phase II Trial of Ribociclib and Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS)

This is a two center, 2 arm, Phase II study evaluating the combination of Ribociclib and Everolimus in patients with advanced DDL and LMS who have had at least 1 prior systemic therapy. Patients will be enrolled by sarcoma histology into DDL (Arm A) and LMS (Arm B). The purpose of this study is to determine the anti-tumor activity of this doublet therapy in these patient cohorts. Ribociclib will be administered orally at 300 mg/day 3 weeks on/1 week off. Everolimus will be administered 2.5 mg orally on a continuous 28 day cycle. Clinical and laboratory assessments will be made on day 1, d15 of cycle 1 and 2, and day 1 of each subsequent cycle. Tumor response will be assessed by RECIST 1.1 at (CT or MRI) at week 8, 16, 24 and every 12 weeks thereafter. Study drug administration will continue until disease progression, unacceptable toxicity or withdrawal of consent. Patients will be followed until death or are lost to follow-up for analysis of secondary endpoints. There will be a 1 step registration process for dedifferentiated liposarcoma patients while patients with leiomyosarcoma will require a 2 step registration process. For step 1 of registration, patients must meet all the eligibility criteria necessary for step 1. For step 2 registration, patients must meet the inclusion criteria necessary for step 2 to be enrolled into the study.

Study to Assess TOPO2A as a Biomarker for Sensitivity to Doxorubicin/Doxil in Soft Tissue Sarcoma

The primary aim of this study is to determine the utility of TOPO2A as a biomarker for sensitivity to doxorubicin or its derivatives. Patients whose planned therapy is doxorucibin or doxil single agent may be enrolled into this trial. In light of its recent FDA approval and differing mechanism of action, patients receiving olaratumab along with doxorubicin will be eligible for this study. Doxorucibin will be administered at standard 21-day intervals. Doxil will be administered at standard 28-day intervals. Response to therapy will be assessed using standard RECIST criteria every 2 cycles. Patients will continue on study until disease progression, prohibitive toxicity or completion of cumulative dose of 450 mg/m2 of either agent. Overall survival will be assessed every 3 months for 1 year, every 6 months in year 2 and, annually until death.

SATURN-STS: Phase II Study of Neoadjuvant Atezolizumab With Doxorubicin, Concurrent Atezolizumab With Pre-operative Radiation Therapy and Adjuvant Atezolizumab in Patients With High-risk Surgically Resectable Extremity and Truncal Soft Tissue Sarcoma

The goal of this clinical research study is to look at the effectiveness of giving a combination of chemotherapy, immunotherapy, radiation therapy, and surgery to treat soft tissue sarcomas that can be removed by surgery. Researchers want to find out if this treatment combination can extend the time it takes for the disease to relapse (come back after treatment). The safety of this treatment combination will also be studied.

A Study of LVGN6051 Combined With Anlotinib in Patient With Soft Tissue Sarcoma

The purpose of this study is to asess the safety and tolerability and efficacy of LVGN6051 combined with anlotinib in patient with soft tissue sarcoma.

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

3CAR is being done to investigate an immunotherapy for patients with solid tumors. It is a Phase I clinical trial evaluating the use of autologous T cells genetically engineered to express B7-H3-CARs for patients ≤ 21 years old, with relapsed/refractory B7-H3+ solid tumors. This study will evaluate the safety and maximum tolerated dose of B7-H3-CAR T cells.The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give to patients with B7-H3-positive solid tumors. Primary objective To determine the safety of one intravenous infusion of autologous, B7-H3-CAR T cells in patients (≤ 21 years) with recurrent/refractory B7-H3+ solid tumors after lymphodepleting chemotherapy Secondary objective To evaluate the antitumor activity of B7-H3-CAR T cells Exploratory objectives * To evaluate the tumor environment after treatment with B7-H3-CAR T cells * To assess the immunophenotype, clonal structure and endogenous repertoire of B7-H3-CAR T cells and unmodified T cells * To characterize the cytokine profile in the peripheral blood after treatment with B7-H3-CAR T cells

A Study Evaluating the Safety, Pharmacokinetics and Early Efficacy of AVA6000 in Solid Tumours

This is a first-in-human (FIH), Phase 1 open-label, multicentre dose escalation study investigating AVA6000 monotherapy administered intravenously in patients with locally advanced (unresectable) or metastatic solid tumours that are likely to be FAP positive. The study consists of an initial Phase 1a dose escalation portion and a subsequent Phase 1b dose expansion portion upon completion of the dose escalation portion.

Study Assessing the Effects of Early Psychiatric Referral on Mental Health and Quality of Life in People With Sarcoma

The purpose of this study is to investigate the feasibility of early access to mental healthcare during sarcoma treatment as well as to assess the association between early access to psychiatric care and depression, anxiety, postoperative outcomes, and patient satisfaction in patients undergoing surgery for musculoskeletal sarcoma.

Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery

This phase II trial studies the side effects of talimogene laherparepvec and radiation therapy and to see how well they work in treating patients with newly diagnosed soft tissue sarcoma that can be removed by surgery (resectable). Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Radiation therapy uses high energy x-rays, photons. electrons, or protons to kill tumor cells and shrink tumors. Giving talimogene laherparepvec and radiation therapy may work better in treating patients with soft tissue sarcoma.

Hypofractionated Radiotherapy for Soft Tissue Sarcomas

One of the main challenges in treating sarcomas with radiation is the toxicity to normal structures around the sarcoma. Early reports suggest Hypofractionated Radiotherapy will be safe and effective for treatment of soft tissue sarcomas. However, given the rarity of this disease, the diversity of histological sub-types, and the variety of locations where these can occur (anywhere in the body), more data is needed to provide understanding of the safety and efficacy of hypofractionated radiotherapy for treatment of this disease. The hypothesis is that by using hypofractionated radiotherapy, highly conformal high dose radiation can be delivered to soft tissue sarcomas, while respecting established normal tissue constraints and that local control rates will be greater than historical rates reported with conventional fractionation. Eligible participants with biopsy proven soft tissue sarcoma will be on study for up to 60 months.

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.

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

To find a recommended dose of attIL2-T cell therapy that can be given to patients with soft tissue or bone sarcomas and to see if it can help to control the disease.

Molecular Profiling of Advanced Soft-tissue Sarcomas

MULTISARC is a randomized multicenter study assessing whether high throughput molecular analysis (next generation sequencing exome - NGS) is feasible in advanced/metastatic soft-tissue sarcoma patients, that is, whether NGS can be conducted for a large proportion of patients, with results available within reasonnable delays. In parallel, MULTISARC aims to assess efficacy of an innovative treatment strategy guided by high throughput molecular analysis (next generation sequencing exome, RNASeq \[NGS\]) in patients with Advanced/metastatic soft-tissue sarcomas. At the end of first-line treatment, participant's tumor profile of experimental Arm NGS (treatment strategy based on NGS results) will be discussed within a multidisciplinary tumor board which aims at discussing the genomic profiles and at providing a therapeutic decision for each participant. Participants for whom a targetable genomic alteration has been identified will be proposed to enter in one of the subsequent phase II single-arm sub-trial.

Phase I Study of [177Lu]Lu-DFC413 in Patients With Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[177Lu\]Lu-DFC413 and safety and imaging properties of \[68Ga\]Ga-NNS309 in patients aged ≥ 18 years with solid tumors

B7H3 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 B7H3-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express B7H3. On Arm A of the study, research participants will receive B7H3-specific CAR T cells only. On Arm B of the study, research participants will receive CAR T cells directed at B7H3 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. Arm A CAR T cells include the protein EGFRt and Arm B CAR T cells include the protein HER2tG. These proteins can be used to both track and destroy the CAR T cells in case of undue toxicity. 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 participant's body on each arm. Participants 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. Participants 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.

Efficacy and Safety of Envafolimab Plus Doxorubicin and Ifosfamide for Advanced Soft Tissue Sarcoma

Soft tissue sarcoma (STS) is a rare, highly heterogeneous malignancy with a poor prognosis. The standard first-line treatment for advanced patients is anthracyclines (doxorubicin, A) combined with ifosfamide (I, AI regimen), but the efficacy is limited, and some subtypes do not respond well. Immune checkpoint inhibitors (ICI) have shown potential in specific STS subtypes. Anthracyclines can induce immunogenic cell death and upregulate PD-L1, providing a theoretical basis for combined immunotherapy. Previous studies have shown that ICI combined with chemotherapy (such as pembrolizumab + doxorubicin) is more effective than chemotherapy alone. Envolizumab is the world's first subcutaneously injected PD-L1 single-domain antibody-Fc fusion protein, with significant advantages: (1) small molecular weight (\~80kDa) and strong tissue penetration; (2) high stability and can be stored at room temperature; (3) convenient subcutaneous injection and good tolerability (Phase II study of MSI-H/dMMR solid tumors ORR 42.7%, grade 3-4 TEAE 15.5%). In 2022, the FDA granted orphan drug designation for the treatment of STS. This study aims to evaluate the efficacy (ORR, PFS, OS, etc.) and safety of Envolizumab combined with an AI regimen (doxorubicin + ifosfamide) as a first-line treatment for advanced STS.

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.

Study of ADI-PEG 20 or Placebo Plus Gem and Doc in Previously Treated Subjects With Leiomyosarcoma (ARGSARC)

To compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.

Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma

In this study, patients with soft tissue sarcoma (STS) will receive ADI-PEG 20 and ifosfamide in combination with radiation as neoadjuvant therapy. In phase I of the study, up to 5 dose levels will be tested to find the recommended phase II dose (RP2D), after which patients enrolling to phase II will be treated at that dose level to assess efficacy.

Pre-operative Hypofractionated Proton Therapy

This study is being done to examine whether proton therapy for certain kinds of sarcomas (extremity and trunk soft tissue) is safe and effective. As part of the study, patients will have five fractions of proton therapy before the participants have surgery for the sarcoma. The study will measure wound complications and functional outcomes / quality of life after the procedures. Patients will be asked to complete questionnaires about the treatment and quality of life from the time of enrollment until about two years after surgery. Otherwise, the participants will have standard of care follow ups with the treatment team.