27 Clinical Trials for Various Conditions
The goal of this clinical research study is to learn if the combination of atezolizumab and tiragolumab can help to control cancers of unknown primary. The safety and effects of this drug combination will also be studied
This phase II trial tests how well a combination of three immunotherapy drugs work for patients with Merkel cell carcinoma that has spread to lymph nodes and/or distant parts of the body and cannot be treated with surgery (advanced or metastatic MCC) and grew despite prior PD-(L)1 therapy. The three drugs INCMGA00012 (retifanlimab, anti-PD-1), INCAGN02385 (tuparstobart, anti-LAG-3), and INCAGN02390 (verzistobart, anti-TIM-3) are monoclonal antibodies given periodically via IV to reactivate the body's immune system to attack the cancer. This combination may stop tumor growth if tumors have grown despite anti-PD-(L)1 therapy alone.
This study will evaluate the safety and effectiveness of a combination of study drugs including zimberelimab, etrumadenant, and quemliclustat in combination with metastasis-directed irradiation in men with hormone sensitive oligometastatic prostate cancer. The study aims to test the hypothesis that targeted inhibition of the adenosine signaling axis (quemliclustat (CD73 antagonist) + etrumadenant (A2AR/A2BR antagonist)) and immune checkpoint inhibition (zimberelimab, α-PD-1) in combination with metastasis-directed stereotactic body radiation therapy (SBRT) will improve local control, progression-free survival (PFS), and hormone therapy-free survival and mitigate immunosuppressive changes to the tumor microenvironment (TME), compared to SBRT alone.
This is a phase I, open label study employing diphencyprone (DPCP) to characterize gene expression changes of various immune cell and tumor markers in cutaneous metastases treated with topical DPCP twice weekly for 12 weeks in combination with PD-1 or PD-L1 immune checkpoint inhibition (ICI), compared to pre-treatment cutaneous metastases and to describe the adverse events associated with DPCP when administered topically twice weekly for 12 weeks in combination with PD-1 or PD-L1 ICI.
Determine the feasibility of liver stereotactic body radiation therapy (SBRT) given in combination with systemic therapy (immune checkpoint inhibitors) in adult patients with metastatic NSCLC with liver metastases.
Background: Glioblastoma (GBM) is a type of malignant glioma. These cancers are nearly always fatal. People who develop these cancers get aggressive treatments. But the tumors almost always recur. Researchers want to study people with newly diagnosed disease to learn more. Objective: To study people with newly diagnosed GBM or gliosarcoma to look at the changes in immune cells in the blood of those who take ipilimumab and nivolumab, along with temozolomide. Eligibility: Adults ages 18 and older with newly diagnosed GBM or gliosarcoma, who have had surgical removal of their tumor and have completed standard initial chemotherapy and radiation therapy. Design: Participants will be screened with the following: Medical record review Medical history Physical exam Tests to assess their nervous system and their ability to do typical activities Blood tests Tumor assessment. For this, they will have magnetic resonance imaging (MRI). They may get a contrast dye through an intravenous (IV) catheter. The MRI scanner makes noise. They will get earplugs. Electrocardiogram. It measures heart rate and rhythm. They will lie still. Sticky pads will be placed on their chest, arms, and legs. Screening tests will be repeated during the study. Treatment will be given in cycles. Each cycle lasts 4 weeks. Participants will get nivolumab and ipilimumab via IV. They will take temozolomide by mouth. They will keep a pill diary. Participants will fill out surveys about their symptoms. Participants will have follow-up visits about 60 days and 100 days after treatment ends. Then they will be contacted every 6 months for the rest of their life.
This trial is a randomized, 2-arm, phase II study to determine the effect, if any, of the timing of stereotactic radiosurgery (SRS) relative to immune checkpoint inhibitor (IO) therapy in patients with non-small cell lung cancer (NSCLC) that has spread (metastasized) to the brain.
This is a pilot study of combination low dose rate brachytherapy (LDR) added to standard of care (SOC) immunotherapy in stage III and IV melanoma, stage IV renal call cancer, and stage IV urothelial cancer.
This is a single-arm, phase I/II trial to determine the Maximum Tolerated Dose (MTD), Recommended Phase II Dose (RP2D), and the safety and efficacy of the combination of nivolumab-ipilimumab plus lurbinectedin in patients with relapsed/recurrent small cell lung cancer after progression with first-line, platinum-based chemotherapy
This is a single-arm, non-randomized pilot study to evaluate the efficacy and tolerability of combination quad-shot palliative radiotherapy with immunotherapy for advanced/recurrent/metastatic head and neck cancer.
The purpose of this study is to determine the impact of pre-operative cryoablation, and immune checkpoint inhibition (ICI) on on 3-year Event Free Survival (EFS), in women with residual hormone receptor negative, HER2-negative ("triple negative") resectable breast cancer after taxane-based neoadjuvant chemotherapy.
This is a phase Ib study to evaluate safety and tolerability of dual checkpoint inhibition (DCI) of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) with SBRT in the treatment of oligometastatic NSCLC. This study will examine the sequential delivery of SBRT to all disease sites followed by combination of durvalumab and tremelimumab for patients for whom the goal is ablating all known sites of disease. The investigators anticipate that for many participants this will be the first line-therapy. Participants who have received prior-platinum-based chemotherapy and/or any line of prior chemotherapy are eligible. Prior immunotherapy treatment is not allowed.
Background: * Immune-based approaches in colorectal cancer have unfortunately with the notable exception of immune checkpoint inhibition in microsatellite instable (MSI-hi) disease been largely unsuccessful. The reasons for this are unclear but no doubt relate to the fact that in advanced disease colorectal cancer appears to be less immunogenic, as evidenced by the lack of infiltrating lymphocytes with advancing T stage * Pexa-Vec (JX-594) is a thymidine kinase gene-inactivated oncolytic vaccinia virus engineered for the expression of transgenes encoding human granulocyte- macrophage colony-stimulating factor (GM-CSF) and beta-galactosidase. Apart from the direct oncolytic activity, oncolytic viruses such as Pexa-Vec have been shown to mediate tumor cell death via the induction of innate and adaptive immune responses * Tremelimumab is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expressed on the surface of activated T lymphocytes and causes inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. Durvalumab is a human monoclonal antibody directed against programmed death-ligand 1 (PD-L1). * The aim of the study is to evaluate whether the anti-tumor immunity induced by Pexa-Vec oncolytic viral therapy can be enhanced by immune checkpoint inhibition. Objective: -To determine the safety, tolerability and feasibility of Pexa-Vec oncolytic virus in combination with immune checkpoint inhibition in patients with refractory metastatic colorectal cancer. Eligibility: * Histologically confirmed metastatic colorectal cancer. * Patients must have progressed on, been intolerant of or refused prior oxaliplatin- and irinotecan-containing, fluorouracil-based, chemotherapeutic regimen and have disease that is not amenable to potentially curative resection. Patients who have a known Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type tumor must have progressed, been intolerant of or refused cetuximab or panitumumab based chemotherapy. * Patients tumors must be documented to be microsatellite-stable (MSS) either by genetic analysis or immunohistochemistry OR microsatellite-high with documented disease progression following anti-programmed cell death protein 1 (PD1)/Programmed death-ligand 1 (PDL1) therapy. * Patients must have at least one focus of metastatic disease that is amenable to pre- and on-treatment biopsy. * Willingness to undergo mandatory tumor biopsy. Design: -The proposed study is Phase I/II study of Pexa-Vec oncolytic virus at two dose levels in combination with immune checkpoint inhibition in patients with metastatic colorectal cancer.
This is an open-label, three-cohort, phase Ib study to determine the safety, recommended phase 2 dose (RP2D), and efficacy of Stereotactic Body Radiation Therapy (SBRT) in combination with either (A) MEDI4736 alone, (B) tremelimumab alone, or (C) the combination of MEDI4736 and tremelimumab for patients with unresectable locally advanced adenocarcinoma of pancreas.
BACKGROUND: * Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response. The term ablative therapies applies to trans-arterial catheter chemoembolization (TACE), radiofrequency ablation (RFA) and cryoablation (CA). * The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE, CA and RFA in patients with advanced hepatocellular carcinoma (HCC) and biliary tract carcinomas (BTC). We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy. * Based on the concept of programmed death-ligand 1 (PDL1)-mediated adaptive resistance and the emerging role of programmed cell death protein 1 (PD1) therapy in HCC, we would like to evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in HCC and BTC. Objectives: - To preliminarily evaluate the 6-month progression free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced HCC (either alone or with cryoablation, TACE or RFA) and in patients with advanced biliary tract carcinoma (BTC) (either alone or with cryoablation or RFA). ELIGIBILITY: * Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma). * Childs-Pugh A/B7 cirrhosis only is allowed. If patient does not have cirrhosis, this limitation does not apply. * Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation. DESIGN: We will evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in cohorts A (HCC; N=40) and B (BTC; N=30). The first N=10 patients in both cohorts will receive tremelimumab and durvalumab only (i.e. No interventional radiologic procedures). * A: Advanced HCC, BCLC# Stage B/C * N= 1st 10 pts: No ablative procedure Cryoablation/RFA/TACE## * Tremelimumab 75mg flat dose every (q)28 days for 4 doses; Durvalumab 1500mg flat dose q28 days until end of study (EOS)### * 40 total: 10 trem+ dur alone; 10 trem+ dur + TACE; 10 trem + dur + RFA; 10 trem + dur + cryo * B: Intra/extra-hepatic cholangiocarcinoma * N= 1st 10 patients (pts): No ablative procedure; RFA/ cryoablation * Tremelimumab 75mg flat dose q28 days for 4 doses; Durvalumab 1500mg flat dose q28 days until EOS### * 30 total: 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem * BCLC = Barcelona clinic liver cancer staging system * For BCLC stage B patients TACE may be repeated as per standard of care * EOS = End of study treatment or meeting any of the off-treatment or off study criteria.
Background: - Stereotactic body radiation therapy (SBRT) is used to treat cancer. It is a way of giving very focused beams of radiation to tumors. Researchers think that the drugs being used in this study might work better when combined with SBRT in people with pancreatic cancer. Objective: - To study the safety and effectiveness of Durvalumab (MEDI4736) and/or tremelimumab with SBRT. Eligibility: - People 18 and older who have pancreatic cancer that has not responded or to chemotherapy. They must be candidates for radiation but not resection. Design: * Participants will be screened with medical history and physical exam. They will have blood tests. Their tumor will be measured using computerized tomography (CT) or magnetic resonance imaging (MRI). * Participants will have their tumor biopsied with a needle. They will have also have a biopsy after cycle 1. * Participants will get 1 or 2 drugs in combination with the SBRT. * For MEDI4736, the duration of each cycle will be 28-days. Participants will get the drug through an intravenous (IV) infusion twice in each cycle (Days 1 and 15). * For tremelimumab, the duration of the first 6 cycles will each last 28 days. Then the duration of the last 3 cycles will change to 12 weeks. Participants will get the drug through an IV once in each cycle. * All participants will have SBRT. Some will get 1 dose of radiation and some will get 5. CT scans will map their tumor. * Participants will have medical history, physical exam, and blood tests in each cycle. They will have a CT scan or MRI every 8 weeks. Cycles will continue for up to 12 months. * Participants will be contacted yearly for follow-up.
This is a Phase 1B study assessing the safety of immune checkpoint inhibition after SBRT in patients with recurrent or metastatic gastroesophageal cancer (limited metastatic disease).
This study is being done to see if patients with metastatic solid tumors (hematologic malignancies and lymphoma excluded) who have a specific genetic mutation in patients' tumor (the SF3B1, U2AF1 or SRSF2 mutation), are more likely to respond to immunotherapy agents that are now commercially available.
Background: Thymoma and thymic carcinoma are diseases of the thymus. Platinum-based chemotherapy is the standard treatment for these diseases. But in many cases, the disease returns after treatment. Researchers want to see if a new drug can help. Objective: To see if bintrafusp alfa (M7824) is an effective treatment for thymoma and thymic carcinoma. Eligibility: People age 18 and older who have thymoma or thymic cancer and their disease returned or progressed after treatment with at least one platinum-containing chemotherapy treatment plan. Design: Participants will be screened under a separate protocol. Their medical, medicine, and treatment history will be reviewed. They will have a tumor biopsy if they do not have a sample. Participants will get the study drug once every 2 weeks as an intravenous infusion. For this, a small plastic tube is put into an arm vein. During the study, participants will undergo the following: Medicine review Physical exam Review of their symptoms and their ability to perform their normal activities Blood and urine tests Thigh muscle scan (using MRI) Tumor assessment (using MRI or CT) Heart and lung function tests Thyroid gland test Skin assessment. Participants may have tumor biopsies. Some of their blood and biopsy samples will be used for gene testing. Participants may take the study drug until their disease worsens or they cannot tolerate treatment. Participants will have follow-up visits 2 and 6 weeks after stopping treatment. Then they will have long-term follow-up visits every 3 months. These may include imaging scans. Visits may be done by phone, with scans (if needed) done at their doctor s office.
Background: Gastrointestinal cancer is one of the most common cancers worldwide. Researchers think an unmet need exists to understand and improve treatment options. They want to see if a combination of drugs can help people with metastatic colorectal cancer. Objective: To see if using a combination of Vascular Biogenics (VB)-111 and nivolumab is safe and will cause colorectal tumors to shrink. Eligibility: People ages 18 and older with microsatellite stable colorectal cancer that has spread to the liver Design: Participants must consent to sample collection protocol 11C0112. Participants will be screened with: Blood tests Scans Tumor samples. If these are not available, participants will have a biopsy. Before they start treatment and with every treatment cycle, participants will have: Physical exams Blood tests Heart tests Before they start treatment and every 4 cycles, participants will have computed tomography (CT) or magnetic resonance imaging (MRI) scans. For these, they will lie in a machine that takes pictures of the body. For the MRI, a soft padding or coil will be placed around their head. Participants will have biopsies before they start therapy. They will have them again after 2 6 weeks on study. On day 1 of 14-day cycles, participants will get one or both study drugs by vein. After they finish treatment, participants will have monthly visits for 3 months. They will have a physical exam and blood tests. If participants stop treatment for reasons other than their disease getting worse, they will have scans about every 8 weeks. This will continue until their disease gets worse. Participants will be contacted by phone or email every 6 months. This will continue for life. ...
Patients with inoperable endometrial cancer have limited treatment options. PD-L1 expression is common in endometrial cancers and RT induces tumor and systemic changes that induce the immune system. The purpose of this trial is to evaluate anti-PD-1/PD-L1 axis therapy in conjunction of standard of care RT for patients with inoperable endometrial cancer in order to establish the safety and efficacy of inducing an anti-tumor immune response.
This trial will evaluate the use of immunotherapy and PARP inhibition in a population with incurable advanced breast cancer associated with a germline BRCA mutation or HDR-defect. The main objective is to examine overall response rate of pembrolizumab (immunotherapy) in combination with Olaparib (PARP inhibitor) in advanced BRCA-mutated or Homology-directed repair (HDR)-defect breast cancer.
This trial is to assess the efficacy of pembrolizumab (MK3475) added to concurrent radiation and gemcitabine in the management of patients with muscle-invasive urothelial cancer who are not candidates for or decline radical cystectomy.
This phase II trial studies how well pembrolizumab, ipilimumab, and aspirin work in treating patients with melanoma that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Aspirin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab, ipilimumab, and aspirin may work better in treating patients with melanoma.
Background: Glioblastoma (GBM) brain tumors almost always return after treatment. When that happens the tumor can never completely be removed by surgery, so most people also receive drugs. Researchers want to see if combining the drugs nivolumab and BMS-986016 may help. Objectives: To study how nivolumab affects the brain s immune system in people who have had glioblastoma brain tumors return. To study how nivolumab and BMS-986016 affect brain tumors. Eligibility: Adults age 18 and older who have had a return of GBM Design: Participants will be screened with: Medical history Physical exam Cheek swab Heart, blood and urine tests Chest x-ray Magnetic resonance imaging (MRI) brain scan. Participants will lie on a table that slides in and out of a cylinder in a strong magnetic field. A contrast agent will be injected in an arm vein. Participants will stay in the hospital. They will: Have surgery. A tube will be inserted into the back. Brain tumor and bone marrow samples will be taken. Tubes will be inserted into the brain. Have a computed tomography brain scan. Stay in Intensive Care (ICU) 7 days. Fluid from the brain and back will be collected every few hours. In the ICU, participants will get nivolumab by IV for 30 minutes. Have surgery to remove the tubes. Have standard surgery to remove as much of the GBM as possible. Bone marrow will be removed. After leaving the hospital, participants will have visits every 2 weeks to get the study drugs by IV and have physical exams and blood tests. Participants will have a brain MRI once a month. ...
Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Most people with advanced HCC survive an average of 6 to 9 months. Researchers are evaluating a combination of treatment drugs to delay the progression of HCC; aiming to help people with HCC live longer. Objective: To study the 6-month progression-free survival in people with advanced HCC treated with bevacizumab, durvalumab, and TACE. Eligibility: Adults ages 18 and older with intermediate or advanced HCC Design: Participants will be screened with a physical exam and medical history. They will have tests to evaluate their hearts as well as blood and urine. A CT and/or MRI scans will be done during the study. If a prior tumor sample is not available; participants may undergo a biopsy. They may undergo an endoscopy of their esophagus and stomach. Participants will get the study drugs in 21-day cycles: Two treatment drugs will be injected into a vein every 3 weeks. Patients will have an interventional treatment procedure done by interventional radiology under sedation; chemotherapy beads will be infused into artery branches in the liver. Participants may have to stay in the hospital for 24 hours for observation, after this procedure. This interventional procedure may be done more than once during the study. Participants may need to repeat some of the screening tests throughout the study. Participants may have to stop taking some of their cancer treatment drugs during the study. Participants will continue on the study until their cancer progresses or until the side effects of the treatment drugs are not tolerable.
The main purpose of this study is to compare the objective response rate (ORR) and overall survival (OS) of bempegaldesleukin (NKTR-214: BEMPEG) combined with nivolumab to that of tyrosine kinase inhibitor (TKI) monotherapy (sunitinib or cabozantinib) in IMDC intermediate- or poor-risk patients and IMDC all-risk patients with previously untreated advanced renal cell carcinoma (RCC).