View clinical trials related to Adrenocortical Carcinoma.
Filter by:This study is a national, multicenter, interventional, phase II clinical trial on the use of pembrolizumab in advanced adrenocortical carcinoma, with confirmed progression within 6 months, following EDP or EDP-M ( etoposide, doxorubicin, cisplatin- mitotan) chemotherapy. Adrenocortical carcinoma is a very rare entity with poor prognosis and limited therapeutic options. Only radical surgical treatment of the early stages gives a chance for complete cure, however the risk of recurrence still remains high. The results of clinical trials conducted outside Poland indicate a possible potential role of immunotherapy as a rescue treatment for adrenocortical carcinoma after standard therapeutic methods have been exhausted. This study will evaluate the efficacy and tolerability of treatment with the immune checkpoint inhibitor pembrolizumab in locally advanced, non-operable or metastatic adrenocortical carcinoma after first line chemotherapy failure. The study population will include adult patients (>18 years of age) with histopathologically confirmed adrenocortical carcinoma and confirmed progression according to RECIST 1.1 within 6 months, after first line chemotherapy with the EDP and EDP-M scheme. Patients must meet the inclusion criteria and must not meet the exclusion criteria described in the PEMBR-01 study protocol. The planned number of patients in the study is 24. The treatment regimen will be based on Pembrolizumab administered intravenously in 3 weeks cycles at a dose of 200mg. For hormonally active tumors producing cortisol, it is hypothesized that the use of pembrolizumab in combination with effective steroidogenesis inhibition may enhance the effect of immunotherapy. In the study, metyrapone or ketoconazole will be used for this purpose. The primary endpoint of the study will be the objective response rate to the treatment. The secondary endpoints will be progression-free survival, duration of response, overall survival, and treatment safety as well as the effect of therapy on patients' quality of life. Concurrently, the analysis of biomarkers in tumor tissue will be carried out, including tumour infiltrating lymphocytes, expression of programmed death ligand, microsatellite instability and tumour mutation burden.
Background: Neuroendocrine neoplasm (NENs)are rare cancers arising from the neuroendocrine cells and can affect almost any part of the body. They vary from low grade neuroendocrine tumors (NETs) to high grade neuroendocrine carcinomas (NECs). These tumors often occur in the gastrointestinal tract, pancreas, lungs, adrenal medulla (pheochromocytomas) or adrenal cortex (adrenocortical cancer) and other areas of the body mentioned below: - Gastroenteropancreatic neuroendocrine tumors (GEP-NET): stomach, duodenum, pancreas, colon, appendix, etc. - Liver and gallbladder - Adrenal tumors - Pituitary gland - Thyroid gland: medullary thyroid carcinoma - Parathyroid tumors - Pulmonary neuroendocrine tumors: typical and atypical carcinoid, small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC) - Extrapulmonary small cell cancer - Peripheral nervous system tumors: paraganglioma, neuroblastoma) - Breast and genitourinary tract Their rates are rising in the United States and worldwide. Researchers want to learn more about NENs through this natural history study. Objective: To study the natural history of people with NENs and obtain samples from them to learn more about the disease. The clinical management of all NETs is not standardized, with only a few FDA-approved therapies and we would like to learn which combination therapeutic approach should be used, how long treatment should be continued, and in what subgroup of NENs a particular treatment option should be used. Eligibility: People aged 18 and older who have or are suspected to have NENs or ACC. Design: Participants will be screened with a medical history. Participants will have a physical exam. Their symptoms and their ability to perform their normal activities will be reviewed. They will have blood and urine tests. Participants will receive recommendations for managing their disease and potential treatment options. They will be able to ask as many questions as they would like. Participants may provide saliva, blood, and stool samples for research. They will give tumor samples from a previous surgery or biopsy. Participants may have optional biopsies. During biopsies, cancer tissue will be obtained using a needle and syringe. Tissue will be taken from the liver, lung, or a lymph node. Participants may have an imaging scan or ultrasound to help locate the tumor or area to be biopsied. They will receive local anesthesia and may be sedated. Participants will complete a questionnaire about their family medical history. Participants will have follow-up visits every 6 months. They will have physical exams and give samples. If their health changes, they may have extra visits. If they cannot visit NIH, they (or their doctor) will be contacted by phone or email. Participants will take part in the study for all their life.
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
Metastasis is the main cause of death in cancer patients and often epithelial-to-mesenchymal transition (EMT) is advocated as the basic mechanism. Recently Fang and colleagues described an EMT-independent process of metastasis in hepatocellular carcinoma (HCC): endothelium covers small cluster of tumor cells allowing tumor dissemination. This process of angiogenesis, named VETC (vessels that encapsulate tumor clusters) in HCC literature, has been described under different names in other cancer types. Furthermore, the investigators confirmed the negative impact of VETC on patients' prognosis on a large multicenter cohort of HCCs. Moreover, Fang et al demonstrated that patients affected by VETC-positive HCC benefit more from sorafenib therapy. Interestingly, this type of angiogenesis was also found in renal cell carcinoma, adrenal gland pheochromocytoma, thyroid follicular carcinoma and alveolar soft part sarcoma (ASPS) and associated to prognosis. Moreover, the distinction between benign and malignant neoplasms of the adrenal gland is a complex matter, being the established criteria still lacking a strong reproducibility. Several tyrosine kinase inhibitors are available for different cancer types; among them, HCC, RCC, ASPS, and TC may benefit from the so-called antiangiogenic tyrosine kinase inhibitors (aTKI) (such as sunitinib, sorafenib, pazopanib). A general (histotype-independent) validation of the prognostic role of VETC is missing. Moreover, inhibitors of tyrosine-kinase vascular endothelial growth factor receptors (VEGFR-TKI), represent an effective treatment for different cancer types, but predictive markers are still needed. In addition, novel systemic immunotherapy agents are being approved in many cancer types, as alternative to angiogenesis inhibitors. A broader frame including metastatic mechanisms, tumor microenvironment (TME, i.e. angiogenesis and immune infiltrate) and treatment response could answer to several needs currently unmet. Bayesian networks and causal models can be employed to effectively draw conclusions from retrospective data. The aim of the present study is to investigate in patients with RCC and adrenal carcinoma (AC) the VETC-expression on tumor tissue, correlating the results with clinical data, patients characteristics, and outcome.
Adrenocortical carcinoma (ACC) is a rare aggressive malignant tumor. According to the literature, the 5-year survival rate of ACC is 12%-47%. For patients with advanced ACC, mitotane alone or combined with traditional chemotherapy was the first-line standard treatment, but its progression-free survival was only about 1 year. However, for patients who fail the first-line treatment, there is a lack of effective treatment. For ACC patients who had failed first-line chemotherapy, a phase II clinical trial found that the objective response rate and the disease control rate of PD-1 inhibitor Keytruda were 14% and 64% respectively, and no grade 3 or 4 adverse events were observed. Anti-tumor angiogenic drugs combined with PD-1 inhibitors have shown impressive clinical data in many solid tumors. This study is aimed to evaluate the efficacy and safety of PD-1 inhibitor camrelizumab combined with apatinib in patients with recurrent or metastatic ACC after standard treatment failure, and to seek new treatment for this population.
This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma. The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patients own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.
This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical study designed to investigate safety, tolerability, PK, and preliminary anti-tumour activity of [225Ac]-FPI-1434 (radioimmuno-therapeutic agent) in patients with solid tumours that demonstrate uptake of [111In]-FPI-1547 (radioimmuno-imaging agent), and to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of repeat doses of [225Ac]-FPI-1434 Injection in patients with solid tumours that demonstrate uptake of [111In]-FPI-1547 (radioimmuno-imaging agent).
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Despite complete resection of early-stage disease recurrence rates in ACC are very high (60%.70%). Patients with Ki67 ≥ 10% are considered at high risk for ACC recurrence, whereas patients with Ki67<10% are considered to have low/intermediate risk for recurrence. No study are ongoing on adjuvant systemic therapy in ACC patients that are at high risk of relapse. These patients represent 70-80% of all ACC radically operated. In this setting mitotane is widely prescribed. The efficacy of mitotane is known to be dependent on the attainment of serum drug levels in the so called therapeutic range that is above 14 mg/l. However, ACC patients with high relapse risk may develop disease recurrence before mitotane serum levels attain the target concentration. Chemotherapy with cisplatin containing regimen was shown to be efficacious in the management of ACC in few phase II trials. Based on the background, there is a strong rationale of administering chemotherapy in radically operated ACC patients with high risk of relapse defined as follows: stage I-III ACC (according to the ENSAT classification) with either microscopically complete resection (R0), microscopically positive margins (R1), or undetermined margins (RX) and Ki67≥10% (for a further definition of this condition, see the study population paragraph). In clinical practice, adjuvant mitotane alone or cisplatin-based chemotherapy or the combination of both are used worldwide in patients at high risk of relapse, but there is no prospective validation of these treatments. The investigators will test the efficacy of the combination of cisplatin plus etoposide (plus/minus mitotane according to the investigator preference) in comparison with the actual best routine practice consisting of mitotane or no therapy (according to the personal belief of clinical investigator). This study is parto of the international trial registry ADIUVO-2 coordinated by MD Anderson Center of Huston (Texas).
Adrenocortical carcinoma is an orphan malignant disease that has a dismal prognosis in advanced stages. Mitotane is the only approved treatment but is limited by severe toxicity. Efficacy of mitotane is unsatisfactory with an objective response rate of ≈20% in monotherapy in selected patients (Megerle et al., JCEM 2018). Cytotoxic chemotherapy with etoposide, doxorubin and cisplatin (EDP) or streptozotocin (Sz) in addition to mitotane (Fassnacht et al., N Engl J Med 2012) succeeded in a progression-free survival of 5.6 months and 2.2 months, respectively in patients with advanced ACC. Objective response rates were 23 and 9%. EDP plus mitotane is therefore considered as standard treatment of ACC. Results by Phan et al. (Cancer Research 2015) demonstrated expression of c-MET and its ligand HGF in ACC and provide a rationale to therapeutically target c-MET in ACC. In a case series of 16 patients with advanced ACC refractory to mitotane (with the exception of one case) and 3 (median, range 0-8)further lines of therapy, single agent treatment with cabozantinib off label resulted in three partial responses and five additional cases of disease stabilization for four months or longer (Kroiss et al., J Clin Endocrinol Metab 2020).
This phase III trial studies how well mitotane alone works compared to mitotane with cisplatin and etoposide when given after surgery in treating patients with adrenocortical cancer that has a high risk of coming back (recurrence). Cortisol can cause the growth of adrenocortical tumor cells. Antihormone therapy, such as mitotane, may lessen the amount of cortisol made by the body. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether mitotane alone or mitotane with cisplatin and etoposide after surgery works better in treating patients with adrenocortical carcinoma.