Neoplasms

Gland and Hormone Related Diseases

All Conditions

Adrenal Gland Neoplasms

Adrenal Gland Diseases

Endocrine Gland Neoplasms

Endocrine System Diseases

Vasoconstrictor Agents

Respiratory System Agents

All Drugs and Chemicals

Micronutrients

Anti-Infective Agents

Epinephrine

Racepinephrine

Epinephryl borate

Iodine

Cadexomer iodine

I-131 Iodocholesterol

Donald A. Podoloff, MD

This is a clinical research study using I-131 Iodocholesterol which is an experimental radioactive chemical that when injected into the vein, is picked up in the adrenal glands and permits visualization with gamma imaging devices. These images are used in diagnosing a variety of adrenal abnormalities.Prior to the injection of I-131 Iodocholesterol, the patient will receive perchlorate capsules to block any uptake of I-131 by the thyroid gland if this is deemed important. The patient will continue to take these capsules throughout the period of imaging, which may last up to 1 week. The injection of I-131 Iodocholesterol will be given into a vein and the patient will return for images on at least 1 and possibly 2 occasions between 3-7 days after injection. If the case requires it, the patient may also be given a steroid in tablet form, dexamethasone, to take orally prior to and after the injection to suppress normal adrenal function so that the abnormal tissues can be more easily detected.

Iodine I-131 Iodocholesterol, Its Use in Adrenal Screening

University of Michigan

M.D. Anderson Cancer Center

Rare Diseases

Carcinoma

Pheochromocytoma

Paraganglioma

Adrenocortical Carcinoma

Paragangliomas 1

Adrenal Cancer

omics identity card

Anne-Paule GIMENEZ-ROQUEPLO

Malignant pheochromocytoma/paraganglioma (MPP) and adrenocortical carcinoma (ACC) are two rare cancer entities with a very unfavorable prognosis. The knowledge on these rare cancers improved thanks to the French COMETE network originally based on two clinical centers (HEGP and Cochin) well organized for clinical and biological samples collection. Over the last 10 years, the COMETE key partners deciphered molecular mechanisms of tumorigenesis and oncogenesis of these tumors and identified molecular signatures discriminating between benign and malignant cancers by integrated genomic approaches. This strategy was highly successful in delivering new diagnostic applications of genomics technologies that now appear as potentially suitable for rapid implementation in routine clinical care.

The main objective of COMETE-TACTIC is to provide an easy-to-use "identity card" of the adrenal tumors that will allow a personalized "à la carte" management of the patient and, when indicated, to the indication of the most accurate molecular targeted therapy.

We hypothesize that the improvement of MPP and ACC diagnosis and of the therapeutic options proposed to affected patients will require,

1. the transfer to routine practice and the prospective validation of the novel diagnostic and predictive biomarkers issued from recent discoveries (genetics, genomics, histological biomarkers);
2. the implementation of the translational research projects based on the COMETE collection to identify circulating diagnostic, prognostic and therapeutic genetic and metabolic biomarkers that could be used as non-invasive "liquid biopsies".

Malignant pheochromocytoma/paraganglioma (MPP) and adrenocortical carcinoma (ACC) are two rare cancer entities with a very unfavorable prognosis. The knowledge on these rare cancers improved thanks to the French COMETE ('COrtex, MEdulla Tumors Endocrines') network originally based on two clinical centers (HEGP and Cochin) well organized for clinical and biological samples collection. Over the last 10 years, the COMETE key partners deciphered molecular mechanisms of tumorigenesis and oncogenesis of these tumors and identified molecular signatures discriminating between benign and malignant cancers by integrated genomic approaches. COMETE has published more than 200 papers and performed seminal work on the pathophysiology and the genetics of MPP and ACC published in high-impact journals.

This strategy was highly successful in delivering new diagnostic applications of genomics technologies that now appear as potentially suitable for rapid implementation in routine clinical care.

The main objective of COMETE-TACTIC program is to design and validate an easy-to-use "identity card" classifying MPP and ACC in clinical routine, using molecular genomic and metabolomic tools combined with histopathological-based tests, to provide a real help for early diagnosis, prognostic as well as a personalized "à la carte" management and treatment to patients with malignant adrenal tumors. Seven teams, with an expertise in genomics of adrenal tumors, or in metabolomics approaches, or in clinical research and statistical analyses collaborate in COMETE-TACTIC. COMETE-TACTIC will be based on an already constituted large cohort of 850 patients that will be enlarged by the prospective enrolment of new cases and biological samples (300 to 450 new cases during the 3 years of the project) via 21 French expert and/or competence centers of COMETE-Cancer Reference center.

Previous COMETE basic studies provided important new insight for the understanding of molecular mechanisms responsible for MPP or ACC. With the transfer of "Omics"-based tests from research laboratories to clinical practice, COMETE-TACTIC is the next step toward a personalized medicine for patients with MPP and ACC. COMETE-TACTIC should speed the transfer in routine clinical care of new biomarkers based on cutting-edge technologies combining advanced pathology assessment and targeted genomics and metabolomics to diagnose malignancy and predict outcome, and thereby facilitating a more accurate, rapid and reliable diagnostic work-up for patients. This personalized management will help to avoid delayed diagnosis and to direct clinical decisions resulting in a better health outcome for the patients. COMETE-TACTIC will offer the access to a precise molecular classification of MPP and ACC that should guide targeted therapies. Finally, COMETE-TACTIC will investigate for the first time the impact of circulating biomarkers for the diagnosis and prognostic of adrenal cancers that will be further tested as biomarkers of response to targeted therapies.

Towards an Easy-to-use Adrenal Cancer/Tumor Identity Card

The COMETE Network, Towards an Easy-to-use Adrenal Cancer/Tumor Identity Card

Number of participants with evidence of metastases

Ministry of Health, France

Institut National de la Santé Et de la Recherche Médicale, France

National Cancer Institute, France

Assistance Publique - Hôpitaux de Paris

Central Nervous System Depressants

Fluorodeoxyglucose F18

Etomidate

Hypnotics and Sedatives

Anesthetics

Anesthetics, Intravenous

Anesthetics, General

Combined FDG PET and Iodometomidate imaging prior adrenal surgery of uncertain adrenal neoplasms

2 consecutive imaging studies (diagnostic study) within 1-2 weeks: FDG-PET and 123I-Iodometomidate imaging in patients with an indeterminate adrenal neoplasm

FDG positron emission tomography

Iodometomidate imaging

Bruno Allolio, Professor

Hahner Stefanie, MD, PhD

Andreas Buck, Professor

Stefanie Hahner, MD, PhD

Stefanie Hahner, PD Dr.

Adrenal masses are highly prevalent and detected with high frequency by conventional imaging. Conventional imaging often fails to rule out a malignant lesion. Accordingly, most hormonally inactive adrenal masses removed by surgery are benign adenomas for which surgical removal is unnecessary and poses an avoidable risk to the patients. We hypothesize that the combination of FDG-PET and 123I-Iodometomidate imaging has the potential to noninvasively identify benign adrenocortical adenomas with high accuracy, thereby avoiding unnecessary surgery. Uptake of 123I-Iodometomidate by the adrenal mass demonstrates the presence of CYP 11B enzymes which specifically bind metomidate with high avidity establishing the adrenocortical origin of the lesion, while low uptake of FDG-PET in an adrenocortical lesion establishes its benign nature and excludes the presence of adrenocortical cancer (ACC). The proposed trial will assess the sensitivity, specificity, positive and negative predictive value of the combined imaging for the diagnosis of adrenocortical adenoma. A secondary focus is on the performance of the combined test for differentiating ACC from non-ACC lesions. We expect that the results of our trial will help to greatly reduce the need for surgery in hormonally inactive adrenal masses.

Histopathology of a surgically removed adrenal mass by an expert surgeon is considered to be the gold standard for the differential diagnosis of an adrenal neoplasia. Thus we will only recruit patients scheduled for surgery for an adrenal mass of uncertain origin. Patients will be eligible for the trial when an adrenal mass has been discovered and standard imaging (CT and/or MRI) has not led to a clear characterization of the malignant potential of the lesion (Hounsfield units in unenhanced CT ≥10). In addition, patients with adrenal neoplasia will be only recruited when a hormonally active lesion has been excluded and surgery is planned because of a perceived risk of malignancy. Patients will be evaluated by both \[123I\]Iodometomidate SPECT/CT and \[18F\]fluorodeoxyglucose PET/CT. Computed tomography will be performed as low dose CT of the adrenal region. Imaging can be started with either \[123I\]Iodometomidate SPECT/CT or \[18F\]fluoro- deoxyglucose PET/CT and can be performed at two consecutive days. The time interval between \[123I\]Iodometomidate SPECT/CT and \[18F\]fluorodeoxyglucose PET/CT should not exceed 6 weeks. Patients will have a follow up visit 2-4 weeks after \[123I\]Iodometomidate SPECT/CT and \[18F\]fluorodeoxyglucose PET/CT (or immediately before surgery, if earlier than 2 weeks post imaging). Thirty days after surgery patients will be contacted by phone for assessment of adverse events related to surgery.

Combined FDG-PET and 123I-Iodometomidate Imaging for Adrenal Neoplasia

￼Combined 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) and 123I-Iodometomidate (123I-IMTO) Imaging for Adrenal Neoplasia

Adverse events as well as standard routine parameter changes from before imaging to prior surgery will be assessed (plus follow up analysis until 30 days after surgery)

Diagnostic study with combined FDG-PET and 123I-IMTO imaging in which an indeterminate adrenal mass with negative FDG-PET test (FDG-) and positive 123I-IMTO test (IMTO+) is diagnosed as a benign adrenocortical adenoma (AA+). Primary efficacy endpoint: Specificity (rate estimation) of the diagnostic AA test and likelihood ratio of a positive diagnostic test (using rate estimation of the sensitivity). The outcome measure does not assess a change but the diagnostic accuracy of both FDG-PET and IMTO imaging.

Sensitivity of the diagnostic adrenocortical adenoma (AA) test and likelihood ratio of a negative diagnostic AA test, a priori rates of AA, adrenocortical cancer (ACC) and other benign as well as malignant indeterminate adrenal neoplasias. Detection rates similar to sensitivity and specificity for ACC and indeterminate adrenal neoplasias other than AA and ACC of combined 18F-FDG-PET imaging and 123I-Iodometomidate imaging in identifying ACC. Predictive values will be determined and economic analysis of cost effectiveness of diagnostic evaluation versus surgery for all indeterminate lesions will be performed. The outcome measure does not assess a change but the diagnostic accuracy of both FDG-PET and IMTO imaging.

Charite University, Berlin, Germany

Heinrich-Heine University, Duesseldorf

University Hospital, Essen

Johannes Gutenberg University Mainz

Ludwig-Maximilians - University of Munich

Hannover Medical School

University of Leipzig

University of Florence

University of Padova

Cambridge University Hospitals NHS Foundation Trust

University Medical Center Nijmegen

Uppsala University Hospital

University of Vienna

Wuerzburg University Hospital

Hormones

To collect adrenal tumor tissue biopsy samples in order to study and evaluate new methods that may help identify cancerous or precancerous cells. Participants who have a large tumor or one that secretes hormones will have standard surgery to remove the tumor.

Participants whose tumor does not secrete hormones will have a tumor biopsy to collect tissue for the study.

Tumor tissue biopsy

Participants who have a large tumor or one that secretes hormones will have standard surgery to remove the tumor. Tissue will be collected for study.

Surgery

Naris Nilubol, M.D.

Background:

- Tumors of the adrenal gland are common. Most of them are not cancerous. However, there are no tests that can accurately tell which adrenal tumors are cancerous and which are not. The only way to tell is to remove the tumor with surgery and then examine it. Researchers have been using new methods to study samples of adrenal tissue. These methods may help identify whether the cells are or may become cancerous without an operation. This information will help doctors determine which tumors will need to be removed.

Objectives:

- To collect adrenal tumor tissue biopsy samples in order to study and evaluate new methods that may help identify cancerous or precancerous cells.

Eligibility:

- Individuals at least 18 years of age who have an adrenal tumor that may or may not be cancerous.

Design:

* Participants will be screened with a physical examination, medical history, blood and urine tests, and imaging studies.
* Participants will be examined to determine whether they have a specific type of adrenal tumor

(pheochromocytoma).

* Participants whose tumor does not secrete hormones will have a tumor biopsy to collect tissue for study.
* Participants who have a large tumor or one that secretes hormones will have standard surgery to remove the tumor. Tissue will be collected for study.
* Researchers will examine the collected tissue. They will try to determine whether the cells are cancerous or may become cancerous.
* Participants will be asked to return to the National Institutes of Health Clinical Center every year for about 5 years. During these visits they will have imaging studies, lab tests, and a physical examination.

Background:

* Adrenal neoplasms are common and are incidentally discovered in 4-10% of abdominal imaging studies.
* The majority of adrenal incidentalomas are cortical adenoma.
* Many patients with nonfunctioning adrenal incidentalomas undergo adrenalectomy to exclude a cancer diagnosis.
* There are no reliable clinical, radiographic or laboratory studies that accurately distinguish between localized benign and malignant adrenal neoplasm.
* This protocol is designed to determine the feasibility and accuracy of using novel molecular markers of malignant adrenal neoplasm in fine needle aspiration (FNA) biopsy and surgically resected samples.

Objectives:

* Primary Objectives:

  * To evaluate the feasibility of molecular testing in adrenal neoplasm FNA biopsy samples.
  * To determine the accuracy of novel diagnostic molecular markers in clinical adrenal FNA biopsy and surgically resected samples.
* Secondary Objectives:

  * To analyze the gene expression level relative to disease-free survival and overall survival in patients with adrenocortical carcinoma

Eligibility:

* An individual with an adrenal neoplasm greater than 2cm in size
* Age greater than or equal to 18 years
* Adults must be able to understand and sign the informed consent document

Design:

* Prospective observational study.
* Demographic, clinical, laboratory and pathologic data will be collected for each patient participant. Data will be securely stored in a computerized database.
* Patients will have biochemical testing to determine if their adrenal neoplasm is functioning or nonfunctioning.
* After their initial on-study evaluation, patients who are found to have a nonfunctioning adrenal tumor with a low risk of malignancy will be re-screened every year for 5 years with non-invasive imaging studies.
* Treatment of patients with an adrenal neoplasm will be performed based on standard clinical practice.
* Projected accrual will be 50 patients per year for a total of 10 years. Thus, we anticipate accruing 500 patients on this protocol.

Evaluation of Molecular Markers in Adrenal Tumors

Evaluation of Diagnostic and Prognostic Molecular Markers in Adrenal Neoplasm

Feasibility of molecular testing in adrenal neoplasm fine needle aspiration (FNA) samples was determined by immunohistochemistry. Ribonucleic acid and deoxyribonucleic acid was extracted from fine needle aspiration and tumor tissue samples to differentiate between normal and abnormal tissue.

Tumor tissue obtained via FNA and surgical resection were to be analyzed for molecular markers to help determine if cells were cancerous or may become cancerous.

Gene expression levels were to be analyzed relative to disease free and overall survival in patients with adrenocortical carcinoma.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

National Cancer Institute (NCI)

Principal Investigator

Adrenal neoplasms are common and are incidentally discovered in 4-10% of abdominal imaging studies. Most adrenal tumors are not cancerous. The majority of adrenal incidentalomas are cortical adenoma. Many patients with nonfunctioning adrenal incidentalomas undergo adrenalectomy to exclude a cancer diagnosis. There are no reliable clinical, radiographic or laboratory studies that accurately distinguish between localized benign and malignant adrenal neoplasm.

Adrenal Gland Neoplasm

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Naris Nilubol

Because the study was terminated due to poor accrual and all fine needle aspiration (FNA) samples were benign, molecular testing cannot be performed in the absence of cancerous tumors. Molecular testing was not done in any samples collected.

Feasibility of Molecular Testing in Adrenal Neoplasm Fine Needle Aspiration (FNA) Samples

Determine the Accuracy of Novel Diagnostic Molecular Markers in Clinical Adrenal Fine Needle Aspiration (FNA) Biopsy and Surgically Resected Samples

To Analyze the Gene Expression Level Relative to Disease-free Survival and Overall Survival in Patients With Adrenocortical Carcinoma

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

Overall Study

Digestive System Diseases

Heart and Blood Diseases

Blood and Lymph Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Pancreatic Neoplasms

Aneurysm

Aortic Aneurysm

Aortic Aneurysm, Abdominal

Liver Neoplasms

Lymphadenopathy

Multiple Pulmonary Nodules

Solitary Pulmonary Nodule

Kidney Neoplasms

Neoplasms, Adnexal and Skin Appendage

Vascular Diseases

Aortic Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Liver Diseases

Lymphatic Diseases

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

The Case Group will target consenting 141 participants from the cases with indeterminate but potentially significant findings (E3/E4s) other than pulmonary nodules.

The Pulmonary Nodules Case Group will comprise 119 cases with E3/E4 ECFs characterized as pulmonary nodules.

The E1 Control Group will be drawn from the 866 E1 ECF cases from ACRIN 6664 to create a cohort of 260 E1 ECF cases. The Control Group for comparison with the Case Group and the Pulmonary Nodules Case Group will be selected at the Biostatistics and Data Management Center (BDMC). The BDMC will match E1 141 controls to the 141 case-group participants with indeterminate but potentially significant findings (E3/E4s). The BDMC will also match 119 E1 controls to the 119 E3/E4 pulmonary nodules cases. Controls will be matched by site, age caliper (5 years), and sex where possible.

Hanna M. Zafar, MD, MHS

The ACRIN 7151 trial will use medical records abstraction data from participants with extracolonic findings (ECFs) reported from the ACRIN 6664 National CT Colonography Trial to: 1) measure incidence of diagnostic imaging, hospitalization, and interventional procedures associated with ECFs reported on computed tomography colonography (CTC), delineated by type of ECF; 2) determine potential predictors of follow-up diagnostic imaging, hospitalization, and interventional procedures, delineated by type of ECF; and 3) evaluate the clinical/pathologic diagnoses associated with indeterminate but potentially significant ECFs. These data can be used to incorporate ECFs into existing models on the cost-effectiveness of CTC in colorectal cancer screening and can potentially be used to develop guidelines for the reporting and management of ECFs.

The original ACRIN 6664 National CT Colonography Trial included 15 participating sites and a total study data set of 2531 participants. The target study data set for the ACRIN 7151 trial is 520 participants, assigned to one of three cohorts: an E3/E4 Case Group (n = 141) excluding pulmonary nodules, an E3/E4 Pulmonary Nodules Case Group (n = 119), and an E1 Control Group (n = 260) (see Section 8.6). Medical records will be collected by the site from their institutions and from the primary care provider identified by the participant during the ACRIN 6664 trial. Initial record collection will comprise the six months following CTC for all cohorts. Additional medical record collection (from other primary care providers, specialists, and hospitals, and for extended time periods) may be necessary for primary endpoint determination. ECFs are categorized according to the original radiology read of the CTC during the ACRIN 6664 trial.

Extracolonic Findings on Computed Tomography (CT) Colonography

Incidence and Significance of Extracolonic Findings on CT Colonography: Retrospective Analysis of "National CT Colonography Trial" Data

Estimate the rates of follow-up diagnostic imaging, hospitalization, and interventional procedures commonly associated with ECFs within six months of receiving CTC for all three cohorts (E3/E4, pulmonary nodules, and E1). Compare the rates of medical utilization among participants with indeterminate but potentially significant ECFs (E3/E4s) and participants with pulmonary nodules, to participants with no ECFs (E1s).

Categorize the outcome of potentially clinically significant findings detected by CTC into resolved and unresolved, significant and insignificant at six-months post-examination based on medical record abstraction among participants with indeterminate but potentially clinically significant ECFs (E3/E4s) and participants with pulmonary nodules. Estimate the relationship between participant characteristics and clinically significant findings for participants with E3/E4 ECFs and participants with pulmonary nodules.

Estimate the relative risk of confirmed clinically significant findings within six months of receiving CTC among participants with indeterminate but potentially significant ECFs (E3/E4s) and participants with pulmonary nodules, compared with participants with no ECFs (E1s).

Determine potential predictors associated with increased likelihood of receiving follow-up diagnostic imaging, hospitalization, and interventional procedures within six months of receiving CTC among participants with indeterminate but potentially significant ECFs (E3/E4s), including participants with pulmonary nodules.

Estimate differences in cost associated with common expected follow-up diagnostic imaging, hospitalizations, and interventional procedures within six months of receiving CTC among participants with indeterminate but potentially significant ECFs (E3/E4s) and participants with pulmonary nodules, compared with participants with no ECFs (E1s).

American College of Radiology Imaging Network

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Iodine I-131 Iodocholesterol, Its Use in Adrenal Screening	NCT00037843	Adrenal Gland D... Adrenal Gland N...	I-131 Iodochole...	18 Years -	M.D. Anderson Cancer Center
Towards an Easy-to-use Adrenal Cancer/Tumor Identity Card	NCT02672020	Adrenal Gland N...	omics identity ...	15 Years -	Assistance Publique - Hôpitaux de Paris
Combined FDG-PET and 123I-Iodometomidate Imaging for Adrenal Neoplasia	NCT02010957	Adrenal Gland N...	FDG positron em... Iodometomidate ...	30 Years -	Wuerzburg University Hospital
Evaluation of Molecular Markers in Adrenal Tumors	NCT01348698	Adrenal Gland N...	Tumor tissue bi... Surgery	18 Years - 90 Years	National Institutes of Health Clinical Center (CC)
Combined FDG-PET and 123I-Iodometomidate Imaging for Adrenal Neoplasia	NCT02010957	Adrenal Gland N...	FDG positron em... Iodometomidate ...	30 Years -	Wuerzburg University Hospital
Extracolonic Findings on Computed Tomography (CT) Colonography	NCT01465425	Solitary Pulmon... Multiple Pulmon... Renal Neoplasms Adrenal Gland N... Aortic Aneurysm... Liver Neoplasms Adnexal and Ski... Lymphadenopathy Pancreatic Neop...		50 Years -	American College of Radiology Imaging Network
Extracolonic Findings on Computed Tomography (CT) Colonography	NCT01465425	Solitary Pulmon... Multiple Pulmon... Renal Neoplasms Adrenal Gland N... Aortic Aneurysm... Liver Neoplasms Adnexal and Ski... Lymphadenopathy Pancreatic Neop...		50 Years -	American College of Radiology Imaging Network
Towards an Easy-to-use Adrenal Cancer/Tumor Identity Card	NCT02672020	Adrenal Gland N...	omics identity ...	15 Years -	Assistance Publique - Hôpitaux de Paris

Spots Global Cancer Trial Database for adrenal gland neoplasms