Clinical Research Directory

Atezolizumab Plus Tivozanib in Immunologically Cold Tumor Types

Checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance, and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not currently thought to be an effective intervention in the treatment of several immunologically "cold" tumors such as prostate cancer, biliary tract cancers, soft tissue sarcomas, well-differentiated neuroendocrine tumors, microsatellite stable colorectal cancer, pancreatic cancer, and non-triple negative breast cancer. Vascular endothelial growth factor (VEGF) is thought to play a key role in modulating the anti-tumor immune response. Vascular endothelial growth factor (VEGF) is secreted by tumors and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This in turn leads to the development of an abnormal vasculature with excessive permeability and poor blood flow, limiting immune surveillance. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Vascular endothelial growth factor (VEGF). VEGF tyrosine kinase inhibitors (TKIs) VEGF-TKIs are currently utilized in the treatment of a variety of malignancies and are widely utilized in combination with checkpoint blockade in the treatment of clear cell kidney cancer. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade even in tumors which have traditionally been thought to be unresponsive to immunotherapy. This study aims to evaluate the combination of the immune checkpoint inhibitor atezolizumab and the VEGF-TKI tivozanib in a variety of tumors which have a low response rate to checkpoint inhibitor therapy alone.

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.

Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions

This randomized prospective open-label phase 2 trial testes the safety and feasibility of a hypofractionated accelerated neoadjuvant proton or carbon ion radiotherapy based on the rate of wound healing disorders from beginning of radiotherapy to maximum 120 days after the planned tumor resection or discontinuation of treatment due to any reason. The treatment is of shorter duration (2-3 weeks vs. 5 weeks standard treatment), which should please most patients and thus enhance quality of life. The treatment regimen furthermore promises a reduced rate of late side effects and significant optimization of the current treatment standards. A phase II trial is mandatory not only for obtaining the safety and feasibility data, but also in order to prepare a concurrent phase III trial. Due to the low incidence of soft tissue sarcoma, only a well prepared multicenter study has a chance to be successfully completed based on previous experiences in trials for seldom tumor entities.

Hypofractionated vs Conventional Fractionated RT in Soft Tissue Sarcomas

This research study is designed to find out if radiation therapy treatment prior to surgery is safe and effective to treat soft tissue sarcomas. 30 participants with soft tissue sarcoma will be enrolled and can expect to be on study for up to 5 years.

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.

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.

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.

Circulating Tumor DNA in Soft Tissue Sarcoma

This research study will collect blood and tumor tissue samples from patients with soft tissue sarcoma to look at circulating tumor deoxyribonucleic acid (DNA). When tumor cells are damaged or die, DNA from the tumor cells are released into the blood stream as the cells break down. This is called circulating tumor DNA. Circulating tumor DNA is an important biomarker that may be used in cancer detection, prediction of treatment response, and disease monitoring.

Individualized Prehabilitation for Enhancing Recovery and Surgical Outcomes in Patients Undergoing Radiotherapy and Surgery for Soft Tissue Sarcoma

This clinical trial evaluates whether patients with deep soft tissue sarcomas who receive a tailored prehabilitation exercise regimen during standard radiotherapy and prior to standard of care surgery have better recovery and surgical outcomes than those who do not. Patients undergoing surgery to soft tissue sarcomas are at high risk for post-operative disability, which is associated with high rates of depression and poor health-related quality of life. Prehabilitation is the practice of exercising before surgery to ensure that the patient is in the best possible condition. It allows patients to prepare their bodies for recovery after surgery, which may result in better surgical outcomes, recovery, and quality of life after surgery.

In Situ Immunomodulation With CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients w/ Unresectable and Metastatic Solid Tumors

This phase I trial evaluates the safety and effectiveness of in situ immunomodulation with CDX-301, radiotherapy, CDX-1140 and Poly-ICLC (Cohort A) and these with intravenous (IV) pembrolizumab and subcutaneous (SC) tocilizumab (Cohort B) in treating patients with unresectable and measurable metastatic melanoma, cutaneous squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or HER2/neu(-) breast cancer. CDX-301 may induce cross-presenting dendritic cells, master regulators in the immune system. Radiation therapy uses high energy to kill tumor cells and release antigens that may be picked up, processed and presented by cross-presenting dendritic cells. CDX-1140 and Poly-ICLC may activate tumor antigen-loaded,cross-presenting dendritic cells, and generate tumor-specific T lymphocytes, a type of immune cells, that can search out and attack cancers. Giving immune modulators and radiation therapy may stimulate tumor cell death and activate the immune system.

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.

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

Phase II Study of TAEST16001 in Soft Tissue Sarcoma

The main purpose of this trial is to evaluate the efficacy and safety of TAEST16001 cells in the treatment of advanced soft tissue sarcoma patients with HLA-A\*02:01 tissue genotype and positive tumor antigen NY-ESO-1 expression.

Anlotinib Maintenance Treatment for Advanced Soft Tissue Sarcoma

Anlotinib is a multi-target receptor tyrosine kinase inhibitor. It can inhibit the angiogenesis related kinase, such as Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor(FGFR), Platelet-Derived Growth Factor Receptor(PDGFR), and tumor cell proliferation related kinase c-Kit kinase. Anlotinib is an efficient second line therapeutic agent in treatment for metastatic soft tissue sarcoma which has been approved in clinical trials (ALTER-0203). Therefore, this study evaluates the safety and efficacy of anlotinib as maintenance treatment of disease control in advanced soft tissue sarcoma.

Toripalimab Combined With CAV/IE Regimen

The aim of this study was to investigate the efficacy and safety of CAV/IE chemotherapy combined with toripalimab versus CAV/IE chemotherapy alone in the treatment of patients with advanced or unresectable bone and soft tissue sarcomas who failed in standard treatment.

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.

APX005M and Doxorubicin in Advanced Sarcoma

This phase II clinical trial will evaluate the safety and efficacy of adding APX005M (a CD40 agonistic monoclonal antibody) to doxorubicin for the treatment of patients with advanced soft tissue sarcoma. The investigators believe that doxorubicin, which is currently the standard of care for most advanced sarcomas, could work better when combined with APX005M, which is a type of immunotherapy.

5-Day Preoperative Radiation for Soft Tissue Sarcoma

The purpose of this study is to examine the safety and efficacy of an abbreviated course of preoperative radiation, given over five days, for patients with soft tissue sarcoma of the extremity, trunk or retroperitoneum. This is in contrast to standard preoperative radiation, which is given over 25 days.

Feasibility Study on the Effect of a Methionine-Reduced Diet on Serum Levels in Pts w/ Solid Tumors

This is a pilot clinical trial determining the effect of a Methionine-reduced diet on serum levels in subjects with solid tumors. These are subjects who will receive systemic standard of care cancer therapy.

A Study to Evaluate Pre-operative HYPOfractionated Radiation Therapy in Aged (≥ 70 Years Old) or "Fragile" (≥ 65 Years) Patients With Limb or Trunk Soft Tissue SARComa.

This is a phase II, multicenter, non-randomized study. The main objective is to evaluate the treatment with hypofractionated radiation therapy in neo-adjuvant situations on wound healing in a population of aged patients (≥ 70 years old) or ≥ 65 years of age defined as "fragile" and treated for soft tissue sarcoma. A maximum of 48 evaluable patients will be included in this study. The patients will receive an hypofractionated radiation therapy prior to conservative surgery. Each patient will be followed for up to 3 years after the end of complete treatment (radiotherapy + surgery).

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.

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.

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.

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.