Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Endometrial Neoplasms

Neoplasm Metastasis

Neoplastic Processes

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Tumor specimens from endometrial cancer patients, collected preoperatively and during primary hysterectomy, are investigated.

Tumor biopsy study

Britt Edvardsen, AVD ING

Ingjerd Bergo, Tech

Frederic Amant, MD, PhD

Tjugum Jostein, MD, PhD

Klaus Oddenes, MD

Marie E Engh, Prof

Annetine Staff, MD PhD

Solveig Tingulstad, Prof

Jan A. Rokne, MD

Margareth S. Lode, MD

Janusz Marcickiewicz, MD, PhD

Helga B. Salvesen, Prof., MD, PhD

The purpose of this prospective multicenter trial is to investigate the value of molecular markers in endometrial cancer for predicting lymph node metastasis and prognosis in relation to treatment.

This is a prospective multicenter study to investigate the predictive value of molecular markers in endometrial cancer for lymph node metastasis, prognosis and treatment. For the previously studied tumor markers p53, p16, ER, PR and HER2neu, we want to investigate the expression in curettage material in relation to lymph node metastasis and prognosis among endometrial carcinoma patients. We also want to investigate the distribution of genetic alterations in fresh frozen tumor tissue in order to design prospective randomized treatment trials of metastatic endometrial cancer based on molecular profile. There will be a special emphasis on disturbances in the pathways influenced by new targeted therapy, such as inhibitors of Her2/NEU, EGFR, receptor tyrosine kinase, mTOR, PTEN and hormone receptor pathways.

Tumor specimens from endometrial carcinoma, from curettage and hysterectomy specimens, formalin-fixed and paraffin-embedded and fresh frozen, stored at minus 80 °C, corresponding blood samples with normal DNA

Molecular Markers in Treatment in Endometrial Cancer

Prospective Study of Endometrial Cancer Treatment in Relation to Molecular Markers in Curettage Specimens.

Helse-Bergen HF

Norwegian Cancer Society

University of Bergen

Professor, MD, PhD

Uterine Cervical Neoplasms

Uterine Cervical Diseases

women attending the University of Oklahoma Colposcopy Clinic

Nicolas Wentzensen, M.D.

This study, conducted by the National Cancer Institute and the University of Oklahoma, will look for changes in cervix cells and other samples that may be signs of cervical disease. Human papilloma virus, or HPV, is a common infection of the genitalia in women that usually goes away by itself. If HPV infection does not go away, it might turn into cancer of the cervix, although this is rare. This study will examine why many HPV infections go away and why a few persist and lead to cervical cancer.

Women 18 years of age and older who are referred for colposcopy (examination of the vagina and cervix using an instrument with a magnifying lens) at the University of Oklahoma following Pap smear diagnosis may be eligible for this study. Women will be in one of the following diagnostic categories:

* Cancer: Stage 1-2 only.
* Precancer: Cervical intraepithelial neoplasia (CIN3).
* HPV-infected: Positive for any of the 13 known cancer-causing HPV types, but not diagnosed with cancer or CIN3.
* Normal: Negative for cancer-causing HPV and normal tissue laboratory results.

Participants will undergo the following procedures:

* Questionnaire: Covers demographic information (such as age, race, ethnicity, marital status, etc.), pregnancy history, menstrual and sexual history, contraceptive history, hormone medication history, medical history, smoking history, physical development, family history, and health care access.
* Blood test: 2 tablespoons of blood drawn.
* Colposcopy.
* Procedure to collect a sample of cervical cells and fluids for HPV testing and research.

For the past twenty years, large epidemiologic natural history studies have played a crucial role in achieving our current understanding of cervical neoplasia. We now know that human papillomavirus (HPV) infection is necessary but not sufficient cause of cervical cancer. Cervical pathogenesis evolves as follows: normal 'yields' oncogenic HPV infection 'yields' precancer 'yields' invasive cancer. The majority of women with oncogenic HPV infections will not develop cancer, and most HPV infections, even those with associated cellular changes, regress in 1-2 years, probably eradicated or controlled by cellular immune response. Morevoer, while invasive cancer and precancer are histologically welldefined, the histological classification of low-grade lesions, now better defined as HPV infection, is very heterogeneous and poorly reproducible. Identifying women at highest risk for cancer prior to neoplastic progression is therefore a challenge. At present, we are unable to predict with any accuracy which HPV infections will progress and which are among the majority that regress. Currently, cytologic, histologic, and to some extent, HPV DNA assays are the basis for triage, treatment, and follow-up. While this approach has permitted successful cervical cancer prevention efforts, millions of women are diagnosed each year with HPV infections, and because of the inability to distinguish those who will progress from those who will regress, many women are over-treated as a result. It is therefore of etiologic interest and of public health benefit to develop a method for identifying the HPV-infected women at risk for progressing to precancer and invasion. To develop an accurate and reproducible division of precursor lesions (HPV infection and precancer) will require gaining knowledge about the molecular distinctions at each progressive disease state. Our goal is to therefore comprehensively assess biomarkers of risk for progressive cervical neoplasia, and thus develop a new set of biomarkers that can distinguish those at highest risk of cervical cancer from those with benign infection. Specifically, we will initially implement a cross-sectional study to develop a comprehensive list of potential risk biomarkers by examining cervical tissues of women with normal, HPV infection, precancer, and cancer. They will measure gene expression profiles to gain an accurate and comprehensive in vivo picture of cervical neoplasia carcinogenesis. We propose to then validate the most promising identified candidate biomarkers in a prospective design by assessing their predictive values for key outcomes related to progression (HPV persistence, diagnosis of precancer) or non-progression (HPV clearance).

Cervical Cancer Early Endpoints and Determinants

A Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED)

National Cancer Institute (NCI)

Prostatic Neoplasms

Genital Neoplasms, Male

Genital Diseases, Male

Prostatic Diseases

Male Urogenital Diseases

* PSA testing
* Multiparametric MRI (mp-MRI)
* Radiomics
* MR-guided biopsy (MR-guided and systematic US-guided)
* Molecular Markers (Histological analysis of biopsy cores)

Multiparametric MRI

Radiomics analyses will consist of image intensity normalization, image coregistration and resampling, radiomic feature extraction, combination with clinical and molecular parameters, feature extraction and machine learning, model testing on validation and test cohorts and comparison to existing clinical risk models.

Radiomics

MR-guided targeted prostate biopsies as well as systematic TRUS-guided biopsies (at least 12 cores) will be performed on a fusion-guided biopsy system. The biopsy cores can either be obtained transrectal or transperineal.

MR-guided Biopsy

Molecular markers will be analyzed on the initial and final targeted and systematic biopsy cores. The molecular panel consists of a methylation-specific PCR and a set of highly selected markers that can be detected by immunohistochemistry. The resulting data will be prospectively recorded to enable a retrospective analysis of the prognostic value.

Molecular Markers

Lars Schimmöller, MD

Christian Arsov, MD

Almut Diem

Active Surveillance (AS) is a treatment option in patients with favorable risk prostate cancer. According to the current guidelines patients are monitored by prostate specific antigen (PSA) testing (every 3 months) and regular re-biopsies. Due to histological reclassification and/or patient noncompliance a high number of patients discontinue AS. Nonetheless, because of an increasing number of diagnosed early stage tumors overdiagnosis and overtreatment of patients has become a major clinical problem. Therefore AS is a promising and important tool for patients with low and intermediate risk prostate cancer.

Multiparametric MRI (mp-MRI) in combination with radiomics analysis, MR-guided biopsies, and molecular markers are promising tools to optimize patient selection and observation during AS.

This prospective, single arm, multicenter phase II study evaluates mp-MRI, radiomics, MR-guided biopsies and molecular markers for AS with the primary endpoint of reducing discontinuation based on histologic reclassification.

At the end of this study the results may allow defining a MRI-based pathway to identify and monitor patients suitable for AS supported by radiomics. Thus, the high rate of discontinuation due to misclassification at initial diagnosis will be reduced.

Additionally, this strategy will allow reducing over-treatment of clinically insignificant PCA, and on the other hand, increasing early treatment of higher-risk disease. Monitoring by mp-MRI will reduce the number of prostate biopsies and cores per patient during AS, and thus increase the patient compliance. Finally, such a strategy will reduce the economic burden of treating insignificant prostate cancer.

This prospective multicenter phase II study evaluates multiparametric MRI (mp-MRI), radiomics and MR-guided biopsies for Active Surveillance (AS) of men with low- and intermediate-risk prostate cancer (PCA) with the primary endpoint of reducing the rate of discontinuation of AS based on histologic reclassification in an observation period of 24 months.

Men with low- or intermediate-risk PCA diagnosed by mp-MRI followed by an MR/ultrasound fusion-guided biopsy (FUS-GB) plus systematic ultrasound-guided biopsy (SB) will be included in this study.

During the study observation period PSA values will be obtained every 3 months. After having obtained three values PSA doubling times (PSA-DT) will be calculated at every visit. In case of PSA-DT \<3 years patients will get a repeat mp-MRI and in case of MRI progression a repeat targeted FUS-GB plus SB will be performed. In case of a Gleason score upgrading by the targeted biopsy the patient will discontinue AS and get treatment. In cases of stable MRI or stable Gleason score the patient will continue with PSA controls every 3 months.

In addition all patients with stable PSA values will undergo a mp-MRI after 12 months. If this MRI demonstrates progression the protocol proceeds as mentioned above for patients with PSA-increase. At the end of study (24 months after enrollment), all patients will receive another mp-MRI and FUS-GB+SB.

Prospective Evaluation of Mp-MRI, MR-guided Biopsy, and Molecular Markers for Active Surveillance of Prostate Cancer

Prospective Phase II Trial Evaluating Multiparametric MRI, Radiomics, MR-guided Biopsy, and Molecular Markers for Active Surveillance of Patients With Low- and Intermediate-Risk Prostate Cancer

Reduction of the discontinuation of AS from 25% to 15% of patients after 24 months based on re-biopsy Gleason score upgrading

Comparison of Gleason score upgrades (in %) (Gleason score in units 6-10 )

Improvement of SNR (signal-to-noise ratio)

Subjective Image Quality (5-point scale; evaluated by 2 blinded radiologists; total score from 1=non diagnostic, 2=poor, 3=acceptable, 4=good, to 5=excellent)

Improvement of tumor detection rate (in %)

Heinrich-Heine University, Duesseldorf

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Cholangiocarcinoma

Liver Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Bile Duct Cancer

Primary Liver Cancer

All Drugs and Chemicals

Hematinics

Immunomodulating Agents

Liver Extracts

Subjects with a diagnosis or suspicion of PLC

Anuradha Budhu, M.D.

Tim F Greten, M.D.

Adam Burgoyne, MD, PhD

Robin Kelley

Ruth He

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Ghassan Abou-Alfa

Hien Dang, PhD

Yujin Hoshida

Background:

Primary Liver Cancer is the second most common cause of cancer-related death worldwide. It is the cancer with the fastest rising incidence and mortality in the United States. Researchers want to learn more about liver cancer to help them design better treatments.

Objective:

To better understand liver cancer.

Eligibility:

People ages 18 and older who have liver cancer and had or are planning to have immune therapy

Design:

Participants will be screened with a review of their medical records. They will be asked about their medical history and test results.

Participants will come to the NIH Clinical Center. During this visit, their medical records, test results, imaging studies, and tissue samples (if available) will be gathered. Participants will learn the results of a test to see if they have any mutations known to be connected to cancer. They will learn if there are treatment options for them. Participants will give blood, urine, and stool samples or rectal swabs.

Participants will not have follow-up visits just for this study. If they join another NIH research study and have visits for this other study, their medical records; test results; and blood, urine, and stool samples may be collected. This will occur about every 3 months. If they have a biopsy or surgery on another study or as part of treatment and there is leftover tissue, researchers would like to collect some of that tissue.

Participants will be contacted every 6 months by phone or e-mail. They will be asked about their health. They will provide any medical records, test results, and imaging studies.

Participants will be followed on this study for life.

Background:

Primary liver cancer (PLC) is the 2nd most common cause of cancer-related death worldwide and the one cancer with the fastest rising incidence and mortality in the U.S. PLC consists of two main histological subtypes, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), in which diagnoses and treatment decisions are solely based on their baseline clinical features. However, whether these subtypes are truly distinct or share some fundamental features which can be pursued to improve clinical management is currently unclear. In addition, chronic liver diseases, due to complex etiologies such as viral hepatitis, alcohol consumption, chemicals, parasites or dietary factors, underlie and contribute to liver damage, increasing the risk of HCC and CCA development and progression. Consequently, PLC is clinically and biologically heterogeneous which has impeded biological assessment and clinical treatment.

Despite considerable efforts towards improving diagnosis and development of new treatment modalities, the improvement of PLC patient survival is minimal. For certain patients at early or intermediate disease stages, resection and percutaneous local ablation or Transarterial chemoembolization are available. However, the majority of patients present at advanced stages of disease, where the current gold standard of treatment is sorafenib, providing only a minimal improvement in survival time. PLC therefore remains among the most difficult-to-treat malignancies, with a 5-year survival rate of less than 15% in the United States. Thus, it is imperative that new treatment modalities are developed to limit cancer development and treat advanced PLC.

Immunotherapy (IO) is a promising new approach in PLC treatment. Alterations of the immune system, a component of the revised hallmarks of cancer, is recognized as a central player in carcinogenesis and cancer progression. Thus, strategies to inhibit or re-direct the immune response to the presence of tumors are currently being employed or developed. Immune-checkpoint inhibitors have shown promise in clinical trials of several solid tumors. Of particular note are monoclonal antibody-based therapy to block immune-inhibitory molecules, including programmed cell death protein-1 (PD-1), programmed cell death 1 ligand 1 (PDL-1) and cytotoxic T lymphocyte antigen 4 (CTLA4), which block anti-tumor T cell activity. However, the capacity of these therapies to reduce incidence and progression of PLC are still relatively unknown. Currently, several trials are underway to study the impact of immune checkpoint inhibitors as single agents or in combination with targeted therapy, on PLC development and outcome. Initial findings from Phase I/II clinical trials of PLC are promising but suggest that only certain patients respond to such treatment regimens while others do not or suffer from resistance/relapse. At the moment, it is difficult to determine which patient may benefit from immune therapy, due in large part to the lack of large comprehensive studies, biobank resources of specimens and biospecimen collection in clinical trial protocols, which deter our ability to understand and define critical genomic or genetic factors that contribute to patient response. Hence, we plan to collect PLC patient specimens and clinical data from those undergoing immunotherapies at NIH Clinical Center and a few extramural clinical sites to develop predictors for (a) response or resistance to immunotherapy and (b) acquired resistance to immunotherapy.

Objective:

To establish a biospecimen repository for genomic, genetic and epigenetic analysis to study the biology of PLC development and progression.

Eligibility:

Patients with histologically/ultrasound/imaging confirmed or suspicious lesions of HCC or CCA.

Patients with planned or a history of at least 1 dose of immunotherapy for HCC or CCA.

Age \>= 18 years old at date of study consent

Design:

This will be a long-term multi-center study to comprehensively study patients with primary liver cancer (PLC).

Participants will provide clinical information (including medical history, clinical tests, imaging studies and reports, surgical pathology reports, genetic test results).

Tissue samples, blood, urine and fecal samples will be obtained from participants during this study.

Broad spectrum of scientific experiments, including genomics, metabolome, microbiome and immune monitoring will be performed.

Local physicians will be provided with test results of genomics panel evaluation (TruSight Oncology 500 (TSO-500).

Since long-term follow-up of individuals with PLC is a major feature of the study, local sites intend to maintain active contact with study subjects for as long as possible. Patients will be followed throughout the course of their illnesses, with particular attention to patterns of disease recurrence and progression, response to therapies and duration of responses. National death index data can also be utilized to obtain patient outcome information.

National Translational Science Network of Precision-based Immunotherapy for Primary Liver Cancer

A National Translational Science Network of Precision-based Immunotherapy for Primary Liver Cancer (PLC)

.All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP

Established biospecimen repository for genomic, genetic and epigenetic analysis to study the biology of PLC development and progression

Median amount of time subject survives from the beginning of immunotherapy.

Proportion of patients that have progressive disease after 3 years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Molecular Markers in Treatment in Endometrial Cancer	NCT00598845	Endometrial Neo... Neoplasm Metast...	Tumor biopsy st...	-	University of Bergen
Cervical Cancer Early Endpoints and Determinants	NCT00339989	Cervical Cancer Cervical Intrae... Neoplasia CIN		18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Cervical Cancer Early Endpoints and Determinants	NCT00339989	Cervical Cancer Cervical Intrae... Neoplasia CIN		18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Prospective Evaluation of Mp-MRI, MR-guided Biopsy, and Molecular Markers for Active Surveillance of Prostate Cancer	NCT03979573	Prostate Cancer	Multiparametric... Radiomics MR-guided Biops... Molecular Marke...	-	Heinrich-Heine University, Duesseldorf
National Translational Science Network of Precision-based Immunotherapy for Primary Liver Cancer	NCT04145141	Hepatocellular ... Liver Cancer Cholangiocarcin...		18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for molecular markers