43 Clinical Trials for Various Conditions
The purpose of this study is to learn if intismeran autogene which is an individualized neoantigen therapy (INT; formerly, called messenger ribonucleic acid \[mRNA\]-4157) with pembrolizumab (MK-3475) is safe and prevents cancer from returning in people with high-risk melanoma. Researchers want to know if intismeran autogene with pembrolizumab is better than receiving pembrolizumab alone at preventing the cancer from returning.
The primary purpose of this study is to compare pembrolizumab/vibostolimab to pembrolizumab with respect to recurrence-free survival (RFS). The primary hypothesis is that pembrolizumab/vibostolimab is superior to pembrolizumab with respect to RFS as assessed by the investigator in participants with high-risk resected Stage IIB, IIC, III and IV melanoma.
To generate meaningful data regarding ctDNA that would infer risk of recurrence in stage III melanoma patients.
The purpose of this study is to evaluate the role of neoadjuvant immunotherapy and to demonstrate high pathologic complete response (pCR) and near pCR rates in melanoma participants with clinically detectable nodal disease and a high risk of recurrence. Neoadjuvant immunotherapy aims to enhance the systemic T-cell response to tumor antigens while detectable tumor is still present, inducing a stronger and broader tumor-specific immune response. Of the neoadjuvant approaches studied within melanoma, the neoadjuvant combination of nivolumab and ipilimumab has demonstrated high pCR and near pCR rates that may translate to prolonged clinical benefit.
The purpose of this study is to assess whether postoperative adjuvant therapy with mRNA-4157 and pembrolizumab improves recurrence free survival (RFS) compared to pembrolizumab alone in participants with complete resection of cutaneous melanoma and a high risk of recurrence.
This randomized phase III trial studies how well pembrolizumab works compared with the current standard of care, physician/patient choice of either high-dose recombinant interferon alfa-2B or ipilimumab, in treating patients with stage III-IV melanoma that has been removed by surgery but is likely to come back or spread. High-dose recombinant interferon alfa-2B may help shrink or slow the growth of melanoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether pembrolizumab is more effective than the current standard of care in treating patients with melanoma.
This study is an open-label, pilot study of an autologous tumor cell vaccine.
Background: * Melanoma antigen recognized by T cells (MART-1) is a gene that is present in melanoma cells. * This study tests an experimental treatment that uses the patient's own lymphocytes (type of white blood cell), which are specially selected and genetically modified with a gene called anti-MART-1 transduced cells (F5) to target and destroy their tumor. Some of the cells are given as an infusion and others are given as a vaccine. * The anti-MART-1 F5 cells are currently being studied in other patients in combination with chemotherapy and IL-2 (aldesleukin) therapy. Objectives: -To determine if the anti-MART-1 F5 treatment can improve the immune system's ability to shrink tumors and to prevent melanoma from recurring. Eligibility: * Patients 18 years of age and older whose melanoma has been removed and are currently disease-free, but who are at risk for recurrence. * Patients who do not have ocular or mucosal melanoma. * Patients with tissue type human leukocyte antigens (HLA-A)\*0201). Design: * Workup: Patients have scans, x-rays, laboratory tests, other tests as needed and leukapheresis, a procedure for collecting white cells to modify in the laboratory and later reinfuse into the patient. * Patients are assigned to one of four study groups: * Group 1 receives anti-MART-1 F5 cells by 30-minute infusion through a vein on day 0. * Group 2 receives anti-MART-1 F5 cells on day 0 followed by injections of MART-1 vaccine, which contains MART-1 and an oil-based liquid called Montanide ISA-51 VG. The vaccine is repeated on day 30. * Group 3 receives anti-MART-1 F5 cells on day 0 followed by injections of low-dose IL-2 for 5 days (days 0-4). * Group 4 receives anti-MART-1 F5 cells on day 0 followed by MART-1 vaccine and low-dose IL-2 for 5 days. The vaccine is repeated on day 30. * Recovery: Patients are monitored closely and given medicines to prevent or treat any side effects of therapy. * Leukapheresis: Patients undergo leukapheresis at 1 and 3 months after therapy to collect cells to examine the effects of the treatment on the immune system. * Follow-up: Patients return to National Institutes of Health (NIH) 35 days after completing treatment and then at 3 months and every 6 months thereafter for evaluation with a physical examination, review of side effects, laboratory tests and scans. They have blood tests at 3, 6 and 12 months after treatment and then once a year after that. A biopsy may be requested after treatment ends to examine the effects of treatment on the immune system. All patients return to NIH for a physical examination once a year for 5 years and then complete a follow-up questionnaire for another 10 years.
The purpose of this study is to see if the combination of the two cancer drugs, Dacarbazine (DTIC) and a low-dose of Proleukin (IL2), would provide a less toxic and more effective treatment for melanoma than currently available treatments for people with high-risk melanoma. Dacarbazine (DTIC) and Proleukin (IL2) are both FDA-approved drugs for the treatment of melanoma.
The main goal of this study is to estimate the tumor response rate of temozolomide administered in combination with peginterferon alfa-2b to pediatric patients with unresectable Stage III, metastatic, or recurrent cutaneous melanoma.
This study will evaluate the immunization effects of a vaccine for patients who are at risk for recurrence of their skin cancer. That is, the risk of cancer is higher if melanoma has invaded deep into the skin or lymph nodes. Currently, the only therapy that the U.S. Food and Drug Administration (FDA) has approved for preventing recurrence of melanoma is alpha-interferon. But the research data are controversial. In this study, the vaccine to be used, called gp100, contains a piece of a protein called a peptide, which melanoma cancer cells produce. Patients 16 and older who have had confirmed melanoma surgically removed and whose tissue type is tested as being human leukocyte antigen serotype within HLA-A serotype group (HLA-A2), through a specific blood test, may be eligible for this study. Up to 132 participants will be enrolled. There will be a physical examination and collection of blood samples for tests, and making sure that x-rays and scans are current. Patients will be randomly assigned to four groups. Group 1 will receive the peptide with an adjuvant (assistant) oil-based liquid called Montanide ISA-51, as an injection in the thigh. Group 2 will receive gp100, Montanide, and a cream called imiquimod, which the FDA has approved for treating genital warts and herpes but that may help immune cells in the skin to recognize the vaccine. Imiquimod will be applied to the skin for 5 days. Group 3 will receive gp100 mixed in salt water given as several mini-doses under the skin of the thigh. Group 4 will also receive several mini-doses of gp100 mixed in saline, as well as imiquimod cream applied to the skin for 5 days. All patients will receive the gp100 every 3 weeks for 12 weeks. Every dose is a cycle, with four cycles considered a course of therapy. If the melanoma does not return or patients do not experience side effects from this therapy, then the courses of vaccine will repeated for up to 12 cycles of therapy (3 courses over 33 weeks). Side effects of the peptide vaccination include local swelling, swelling of local lymph nodes, bruising, and pain and redness at the injection sites. There may be chills or fever. Patients will be watched closely for such side effects. To study how the vaccine changes the action of cells in the immune system, patients' white blood cells (lymphocytes) will be obtained, involving a separate informed consent. The procedure, called leukaphersis, requires inserting a needle into the arm, to obtain blood going into a machine, which divides the blood into red cells, plasma (or the serum part), and lymphocytes. The lymphocytes are removed, and the plasma and red cells returned to the patient through a second needle in the other arm. Risks associated with the procedure include fainting, which can be prevented by patients' eating before coming to the lab, and bleeding and infection at the needle site. Patients will undergo leukapheresis will be done about four times: before receiving the vaccine, 3 weeks after the first four doses, and then after 8 cycles and 12 cycles. Patients assigned to the groups receiving imiquimod will be asked to record every time they apply that cream and describe any symptoms developed during the study. All patients will be watched closely for any sign that their melanoma has returned. Before and throughout the study, multiple blood tests will be conducted. The vaccine, Montanide, and imiquimod may increase patients' immune system in fighting off new tumors, but that is not known now. However, the study may provide information that will be useful in treating melanoma patients in the future.
This is a pilot study assessing the safety of the combination of ipilimumab administered concurrently with radiotherapy for patients with locally advanced or unresectable melanoma and patients at high risk for recurrence after resection.
This study is researching an experimental drug called REGN3767, also known as fianlimab (R3767), when combined with another medication called cemiplimab (each individually called a "study drug" or called "study drugs" when combined) compared with an approved medication called pembrolizumab. The objective of this study is to see if the combination of fianlimab and cemiplimab is an effective treatment compared to pembrolizumab in patients that have had melanoma removal surgery but are still at high risk for the recurrence of the disease. Pembrolizumab is an approved treatment in some countries in this clinical setting. The study is looking at several other research questions, including: * What side effects may happen from receiving the study drugs. * How much study drug is in the blood at different times. * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects). Antibodies are proteins that are naturally found in the blood stream that fight infections. * How administering the study drugs might improve quality of life.
This pilot clinical trial studies recombinant interferon alfa-2b in treating patients with melanoma. Recombinant interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of melanoma
The purpose of this study is to see if giving participants quisinostat will prevent participants' uveal melanoma tumor from spreading. The researchers want to find out the effects that quisinostat has on participants' condition.
The goal of this clinical trial is to study the impact of Neoadjuvant ipilimumab and nivolumab for melanoma patients that had recurrence during or after adjuvant anti-PD-1 therapy. Participants will receive 2 cycles of treatment prior to their standard of care surgery. After surgery participants will receive standard of care adjuvant therapy and be followed for response.
Despite the recent notable advances in the treatment of advanced melanoma with application of growing immunotherapies, patterns of response and factors resulting in treatment failure are poorly understood. Moreover, the application of these therapeutics has been limited in the neoadjuvant setting, particularly in earlier stage disease, even though this strategy has improved tolerance and efficacy with other modalities of therapy in other cancer types. Survival remains significantly poorer for thicker and ulcerated lesions with T3b and T4 lesions demonstrating less than 50% survival at 5 years independent of other prognostic indicators. Oncolytic viral therapies (OVT) stimulate or suppress the immune system in different ways to stop cancer cells from growing and intra-lesional OVT has demonstrated comparable efficacy and durability with greater tolerability than most effective systemic therapy. Talimogene laherparepvec (T-VEC) is the only phase III approved intra-lesional therapy in melanoma and has demonstrated significantly improved overall response rate (64%) and bystander effect (34% in uninjected lesions) in the therapeutic setting for advanced disease. The investigators propose an open-label, Phase 2 study of talimogene laherparepvec (T-VEC), in the neoadjuvant setting for patients with high-risk, resectable primary and cutaneous melanoma prior to definitive excision. The central hypothesis of this proposal is that neoadjuvant intra-lesional therapy with T-VEC in high risk early stage melanoma will effectively treat local and subclinical distant disease by enhanced immune recognition, immunomodulation of the nodal basin, and still allow for standard of care surgery. The primary aim of this study will be to evaluate for histologic response of melanoma with secondary aim to determine changes in immune response and draining sentinel nodes as well as relationship of immune phenotype to response rate, stage and nodal burden. The investigators plan for thorough exploratory analysis of genetic and microenvironmental changes to identify actionable targets in incomplete as well as evaluation of changes in sentinel burden and subsequent rates of locoregional disease control, recurrence-free survival and overall survival in long term follow up. The investigators predict that histologic clearance of the primary tumor in the surgical specimen will be associated with improved RFS.
This is an open-label, multi-site, single-arm Phase 2 study of adjuvant nivolumab combined with ipilimumab for the treatment of adult subjects with completely treated high-risk ocular melanoma, as defined in eligibility criteria, without evidence of metastatic disease. All patients enrolled to the study will be treated with nivolumab 240 mg IV every 2 weeks plus ipilimumab 1mg/kg IV every 6 weeks. 1 cycle = 6 weeks. Treatment will continue until disease progression, unacceptable toxicity, patient request to discontinue or completion of treatment. Subjects may receive up to 25 doses of nivolumab and 8 doses of ipilimumab
Vaccine adjuvants are compounds used to increase specific immune responses to antigens, but have minimal toxicity or lasting immune effects on their own. This study investigates the use of dendritic cells as an adjuvant for NY-ESO-1 and Melan-A/MART-1 peptides compared to Montanide® in study subjects with melanoma in complete clinical remission.
The study is designed to determine the 32 month rate of distant relapse in patients with uveal melanoma who are at high risk of recurrence following definitive therapy with surgery or radiation who receive adjuvant crizotinib; and secondarily, the overall survival and disease specific survival in this patient population.
This randomized phase II trial studies how well sunitinib malate or valproic acid works in preventing high-risk uveal (eye) melanoma from spreading to other parts of the body. Sunitinib malate may stop the transmission of growth signals into tumor cells and prevents these cells from growing. Valproic acid may change the expression of some genes in uveal melanoma and suppress tumor growth.
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as tamoxifen and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib together with tamoxifen and cisplatin may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects and how well giving sunitinib together with tamoxifen and cisplatin works in treating patients with high-risk ocular melanoma.
The use of lovastatin may slow disease progression in patients at high risk of melanoma. It is not yet known whether lovastatin is more effective than a placebo in treating patients at high risk of melanoma. This randomized phase II trial studies how well giving lovastatin or placebo works in treating patients at high risk of melanoma.
This study will investigate how genetic and environmental factors contribute to the development of melanoma, a type of skin cancer, and related conditions. Individuals \>=4 weeks with a personal or family history of melanoma or atypical spitzoid/Spitz tumor may be eligible for this study. Participants will: * Fill out one or two questionnaires about their personal and family medical history. * Provide written consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with melanomas, tumors, cancer, or other related illnesses for whom they are the next-of-kin or legally authorized representative. * Donate a blood or cheek cell sample to be used for genetic studies. (The blood sample is collected through a needle in an arm vein. The cheek cell sample is obtained either by gently brushing the inside of the mouth with a soft brush or by swishing a tablespoon of mouthwash and then spitting it into a container.) * Undergo a skin biopsy (removal of a small piece of skin tissue) for genetic study. For this procedure, the area of skin to be removed is numbed with a local anesthetic and a 1/4-inch piece of skin is excised with a cookie cutter-like instrument. The wound is then covered with a band-aid. Participants may be asked to travel to the NIH Clinical Center for evaluation, including a medical history, physical examination, and some of the following procedures: * Full body skin examination to evaluate the type and number of moles and document any evidence of sun damage to the skin. The examination involves all the skin from the scalp to the bottoms of the feet. After the examination, a medical photographer will photograph the skin, with close-ups of skin lesions marked by the examiner. If there are parts of the skin the participant does not want examined or photographed, he or she can tell the examiner. * Blood draw of about 120 milliliters (4 ounces) or less * Skin biopsy * Cheek cell sample * X-rays, ultrasound and magnetic resonance imaging (MRI) studies to detect tumors or changes in tumors or other types of changes in specific tissues. MRI is a diagnostic test that uses strong magnetic fields and radiowaves to examine body tissues. The subject lies on a table that is moved into a large tunnel-like machine (the scanner) for about 45 minutes to 1 hour. When the tests are finished, a doctor will discuss the results with the participant and the need, if any, for clinical follow-up.
Effective communication between physician and patient is fundamental to effective care. The recent introduction of electronic patient on-line portals has the potential to change the communication landscape. The investigators surveyed patients to assess their preferred modality for biopsy notification at 3 institutions with differing patient access to on-line portals, to ascertain what patient preferences are currently and if it has changed from historical preferences. Our hypothesis is that as patients become more familiar with ln-line portals, their preferences will likely reflect familiarity with this modality.
This trial studies how well vemurafenib, cobimetinib, and atezolizumab work in treating patients with high-risk stage III melanoma. Vemurafenib and cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving vemurafenib, cobimetinib, and atezolizumab may work better in treating high-risk stage III melanoma. Giving atezolizumab and tiragolumab together may also work better in treating high-risk stage III melanoma.
This 2-part study will evaluate the safety and efficacy of pembrolizumab (MK-3475) compared to placebo in participants with surgically resected high-risk Stage II melanoma. Participants in Part 1 will receive either pembrolizumab or placebo in a double-blind design every 3 weeks (Q3W) for up to 17 cycles/\~1 year (each cycle = 21 days). Participants who complete the initial treatment of 17 cycles of pembrolizumab in Part 1 and experience disease recurrence may be eligible for re-challenge with pembrolizumab at the same dose and schedule of 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2 in an open label design. Participants who complete the initial treatment of placebo and experience disease recurrence may be eligible to switch over to pembrolizumab 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2 in an open label design. The primary hypothesis of this study is that pembrolizumab increases recurrence-free survival (RFS) compared to placebo. Per protocol, response/ progression or adverse events (AEs) during re-challenge/switch-over in Part 2 will not be counted towards the RFS outcome measure or safety outcome measures respectively.
This is a randomized, double-blind, placebo-controlled biomarker study in renal transplant recipients with actinic damage and a history of basal cell carcinomas and/or cutaneous squamous cell carcinomas. There will be two arms to the study: 1) daily oral UAB30 for 28 days; and 2) daily oral placebo for 28 days. The total duration of the study is anticipated to be 5 years. The hypothesis being tested is that a significantly greater percentage of subjects randomized to oral UAB30 over a period of 28 days will achieve ≥30% reduction in biomarkers of proliferation and ≥30% increase in apoptosis biomarkers than those who receive placebo. Cyclin D1 will serve as the primary biomarker. This investigation will determine whether subjects randomized to UAB30 have an increase in all trans-retinoic acid responsive genes in the skin compared to those receiving placebo. This will include an examination of target effects of UAB30 by evaluating its effects in vivo in humans on the DNA damage response and Src signaling pathways.
The purpose of the study is to determine if ipilimumab is effective in preventing or delaying recurrence and prolongs survival after complete resection of high risk stage III melanoma
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as tamoxifen and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with tamoxifen and cisplatin after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying the side effects and how well giving sorafenib together with tamoxifen and cisplatin works in treating patients with high-risk stage III melanoma.