Active clinical trials for "Adrenocortical Carcinoma"

The study is designed as a Phase II, prospective, non randomized, open-label, single arm, multicenter trial, in which patients with locally advanced or metastatic ACC not amenable to complete surgical resection and progressing to cytotoxic chemotherapy will receive Sorafenib plus metronomic chemotherapy as treatment.The aim of this phase II trial is to evaluate the clinical benefit and toxicity of the combination of Sorafenib plus metronomic chemotherapy in patients with locally advanced or metastatic ACC who progressed after first or second line chemotherapy.

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 cancer (ACC) is a rare aggressive tumor. The treatment of metastatic ACC is challenging and the current available treatments are mitotane, chemotherapy or the combination of both. Prognosis in locally advanced inoperable and metastatic ACC patients still remains poor, the 5-year overall survival being <15%. New treatment strategies are therefore needed. The taxanes are a class of drugs targeting the microtubules that have shown to be effective in the treatment of several malignancies but have not been fully developed in patients with ACC. Cabazitaxel is a new taxoid which promotes the tubulin assembly in vitro and stabilizes microtubules against cold-induced depolymerization as efficiently as docetaxel. Cabazitaxel was selected for development based on a better antiproliferative activity on resistant cell lines than docetaxel. The activity of the drug against several malignancies is currently tested in ongoing prospective studies, but to our knowledge neither preclinical nor clinical studies are currently testing cabaztaxel in ACC. This study is aimed to demonstrate that cabazitaxel is active in ACC, but the drug was never tested before in this clinical setting. A prospective, non-randomized, multicentre, open label, single arm, phase II study will be conducted in patients with advanced ACC. The phase II study will be conducted in 2 different Italian Institutions that are reference centers for ACC.

The improvement of conventional imaging techniques has led to an increased detection rate of different adrenal tumors. Since those tumors can belong to a variety of entities the therapeutic consequences also show considerable variation. In order to definitely determine the type of tumor, invasive procedures like CT guided biopsies are often required, which could be avoided by a tumor specific imaging method. The presently available scintigraphic procedures are either time consuming and lead to high radiation exposure or are technically demanding. The steroidogenic enzymes CYP11B1 (11ß-hydroxylase)and CYP11B2 (aldosterone synthase)are expressed exclusively in the adrenal cortex and therefore represent suitable targets for a specific imaging technique. In our project we evaluate 123I-Iodometomidate which binds to both CYP11B enzymes as radiotracer for adrenal scintigraphy.

RATIONALE: Studying samples of blood and tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. PURPOSE: This research trial studies genes in samples from younger patients with adrenocortical tumor.

This work will evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare them to patients with an adrenal neoplasm and pregnant cohort. All of the individuals were treated at King's Hospital between April 2019 and June 2020. Proteins which will be evaluated during this study, include CBG and TBG.

Background: Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of 1.5 to 2 per million people per year. It has a very poor prognosis with an overall 5-year mortality rate of 75 - 90% and an average survival from the time of diagnosis of 14.5 months. The treatment of choice for a localized primary or recurrent tumor is surgical resection. Patients with recurrent or metastatic disease are infrequently curable by surgery alone. As with most solid tumors, chemotherapy options have limited benefit, although platinumbased therapies have response rates of 25 to 30%. To date no targeted therapy has been shown to be of any value in this disease. The natural history of ACC can vary greatly with some patients surviving only months while others can live with disease for years. The basis for these differing clinical presentations is not known. While one cannot exclude an immune or other host component as responsible for the diverse clinical courses, it is also possible that there may be a genetic basis for this phenomenon. A bio-specimen repository will be a major step towards more comprehensive studies of this very rare and unusual tumor, and allow us to begin to characterize subgroups within the disease. Patients with rare tumors seek expert advice in the management of their care. Dr. Fojo has such expertise and is frequently asked to consult in the care of ACC patients throughout the world. A natural history study would establish a more formal mechanism for such referrals, while allowing the systematic collection of epidemiologic data as well as much needed tumor samples. Objective: -To characterize the natural history of adrenocortical cancer, and in the process, collect blood, and tissue samples to study genetic/biochemical pathways involved in the development and progression of adrenocortical cancer (ACC). Eligibility: Patients greater than or equal to 12 years of age with biopsy-proven ACC Patients greater than or equal to 12 years of age suspected of having ACC Design/Schema: Patients will be offered clinical consultation with treatment recommendations, including standard of care and clinical trial options. Computed tomography scans of the thorax, abdomen and pelvis will be performed for staging purposes as indicated; occasionally, magnetic resonance imaging will be performed for the visualization of lesions in the liver, spine, or other anatomic sites. Medical histories will be documented and patients followed throughout the course of their illnesses, with particular attention to patterns of disease recurrence and progression, response to therapies, duration of responses and hormone production in patients with hormone production as a manifestation of their disease. Tumor growth rates will also be calculated throughout the course of the disease. Blood and tumor samples will be obtained at baseline and at follow-up intervals when surgery is indicated. Tumor samples may include samples harvested at other facilities during or prior to enrollment on this trial. Genetic and epigenetic analysis of tumors and in selected cases expression array analysis will be performed.

This natural history study is collecting health information about infants with adrenal masses found on prenatal and/or neonatal imaging. Gathering information over time from imaging and laboratory tests of infants with adrenal masses may help doctors learn more about the disease and plan the best treatment.

Standard diagnostic work-up for adrenal incidentalomas (AI) consists of periodical biochemical analysis and CT-scanning in case the initial work-up does not demonstrate the presence of hormonal hypersecretion or adrenocortical carcinoma (ACC), respectively. The overall aim of this study is to improve the cost-effectiveness of the diagnostic strategy for AI. Cost-effectiveness of urine steroid profiling (USP) will be compared to the standard diagnostic strategy of repeated CT-imaging.

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.