Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Women at high risk for developing breast cancer

Carol J Fabian, MD

A study to examine the correlations between methylation of various genes associated with breast cancer and proliferation and cytomorphology in breast epithelial cells acquired by random periareolar fine needle aspiration of women at high risk for development of breast cancer.

A study to examine the correlation between gene promotor methylation and benign breast tissue proliferation and cytomorphology collected via random periareolar fine needle aspiration in postmenopausal women at increased risk for breast cancer.

Protocol to Examine Methylation of Tumor Suppression Genes in Women at High Risk of Developing Breast Cancer

QM-MSP, Ki-67, and Cytomorphology of RPFNA Specimens From High Risk Women

University of Alabama at Birmingham

Avon Foundation

National Cancer Institute (NCI)

Johns Hopkins University

Carol Fabian, MD

Professor, Director Breast Cancer Prevention Unit

Symptoms and General Pathology

Disease Susceptibility

Disease Attributes

All Drugs and Chemicals

Estrogens

Giuseppe Giaccone, M.D.

This study will explore whether different forms, or variants, of genes are related to a person s risk of developing breast cancer. The genes that are looked at have no clinical significance today, and thus will not impact your personal healthcare at this time. However, these results may help researchers better understand why some people develop breast cancer and others do not. The study will try to determine:

if people with breast cancer have different gene variants from people without the disease;

if these genetic differences influence a person s susceptibility to breast cancer when they are exposed to certain environmental substances, such as nicotine and estrogen; and

if breast cancer that occurs in families is related to a grouping of these variants.

The study will also look for certain proteins, cells, or other substances in fluid aspirated (by the use of gentle suction; no needles) from the nipple that might represent a pattern, or "fingerprint," indicating increased risk for breast cancer.

Study participants will complete questionnaires on cancer risk factors, diet, and family history. A small blood sample (3 tablespoons) will be drawn for study of genetic differences between people with breast cancer and people who are cancer-free. Nipple aspirations, a noninvasive method to obtain fluid from a women s breast, will be attempted 4 to 6 times, over a 4 6 week period. For this procedure, the subject places a warm moist towel over the breasts for about 20 minutes. The breasts are then cleansed with a rubbing alcohol pad. The subject compresses the breast with both hands and a small plastic cup is inverted over the breast. Suction is applied to a small syringe (no needles) attached to the cup for about 15 seconds. The procedure may be repeated up to 5 times on each breast. Any drops of fluid obtained from the nipple will be collected in a glass tube.

...

Cancer risk, even among those with similar environmental exposures is not uniformly distributed. Although we have been able to identify genetic factors whose variants appear to significantly alter an individual's risk of developing breast cancer (BRCA1 and BRCA2), these genes are likely involved with less than 10% of breast cancer cases. Perhaps more applicable to the general population are genes which, while not directly involved with the oncogenic process, may have variants (polymorphisms) which act indirectly by increasing the risk of an oncogenic change within a cell.

It is the goal of this proposal to look at genes, environment, clinical co-factors, and, if possible, any interactions in breast cancer. The ultimate objective of these studies is to establish an effective way of identifying individuals at greatest risk for cancer. We will evaluate the risk of breast cancer associated with polymorphisms in genes involved in estrogen metabolism and action. We will also evaluate the association of breast density and polymorphisms in genes associated with estrogen metabolism and action. In addition, we will also evaluate nipple aspirate fluid and breast duct lavage fluid as another potential source of promising biomarkers of risk.

Susceptibility to Breast Cancer

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

Amino Acids

Docetaxel

Erlotinib Hydrochloride

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Erlotinib 150 mg/day per os until disease progression or unacceptable toxicity develops

Erlotinib

Docetaxel 75 mg/mq on day 1, every 21 days (3-weekly schedule) or Docetaxel 35 mg/mq 0n day 1,8 and 15 every 28 days (weekly schedule). _Until disease progression or unacceptable toxicity develops

Marina C Garassino, MD

Serena Girelli, Biologist

Giuseppe Nastasi, MD

Vittorio Ferrari, MD

Emanuela Vattemi, MD

Bruno Massidda, MD

Antonio Nuzzo, MD

Gianmaria Fiorentini, MD

Francesco Ferrau, MD

Luciano Isa, MD

Giambattista Roda, MD

Gianbattista Roda, MD

Ornella Gottardi, MD

Daniele Fagnani, MD

Sergio Palmeri, MD

Giorgio Cruciani, MD

Alessandra Zoboli, MD

Franco Spremberg, MD

Giuseppe Grimaldi, MD

Sergio Crispino, MD

Fausto Roila, MD

Claudio Verusio, MD

Andrea Bonetti, MD

Bruno Daniele, MD

Roberto Labianca, MD

Efisio Defraia, MD

Ida Colantonio, MD

Andrea Decensi, MD

Liberato Di Lullo, MD

Antonio Ardizzoia, MD

Gabriella Farina, MD

Maurizio Tomirotti, MD

Paolo Foa, MD

Maria Cristina Locatelli, MD

Maria Cristina Locatelli Locatelli, MD

Elena Piazza, MD

Oscar Alabiso, MD

Luigi Cavanna, MD

Salvatore Tumolo, MD

Ida Pavese, MD

Cora N Sternberg, MD

Enrico Cortesi, MD

Flavia Longo, MD

Maria Mauri, MD

Antonio Contu, MD

Antonio Farris, MD

Giuseppe Valmadre, MD

Alessandro Bertolini, MD

Alberto Scanni, MD

The aim of this study is to assess the superiority of docetaxel in comparison to erlotinib in second line in wild-type EGFR tumour patients.

Erlotinib is registered in all patients affected with NSCLC in second and subsequent lines with a small benefit on Overall Survival. Recent evidence suggest that patients with EGFR mutations have a clear benefit when they are treated with EGFR tyrosine kinase inhibitors, while the role of these drugs in wild-type EGFR patients, that are representing the large majority (about 85-90%), is still unclear and no properly planned trials assessed before this issue. Recently, indirect evidence on subgroup analyses on randomized trial suggest that chemotherapy might be superior to erlotinib in wild-type EGFR patients.

Moreover, several authors do not recommend the use of EGFR determined with immunohistochemistry (IHC) or FISH because they do not reproducibly predict outcome.

For these reasons the protocol was amended in May 2011 in a superiority trial of docetaxel versus erlotinib, while the first version was aimed to assess the interaction with biomarkers.

Tarceva Italian Lung Optimization tRial

Optimization of Erlotinib for the Treatment of Patients With Advanced Non Small Cell Lung Cancer: an Italian Randomized Trial

Mario Negri Institute for Pharmacological Research

Niguarda Hospital

Fatebenefratelli and Ophthalmic Hospital

Alberto Scanni MD

Substance Related Disorders

Nervous System Diseases

Rare Diseases

Drug-Related Side Effects and Adverse Reactions

Neurotoxicity Syndromes

Chemically-Induced Disorders

Eribulin mesylate will be administered according to the European Medicines Agency (EMA) and Italian Medicines Agency (AIFA) approved indications and schedule consists in 1.23 mg/m2 on day 1 and on day 8 of each cycle. Cycles will be repeated every 21 days until progression of disease, unacceptable toxicity, patient refusal or medical decision.

The decision to treat patients with Eribulin is independent from the trial. Patients will be treated and managed according to clinical practice. The physician can choose any further line of treatment after disease progression with Eribulin.

ERIBULIN MESYLATE

Laboratory of Clinical Research Department of Oncology IRCCS

Giovanna Damia, PHD

On March 17th, 2011, the European Commission issued a marketing authorization valid throughout the European Union for Eribulin mesylate (Halaven; Eisai Limited), for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least two chemotherapic regimens for advanced disease.

As the use of Eribulin will be widespread in this tumor setting, a better knowledge of its safety profile outside clinical trials is warranted.

Indeed the possibility to select patients at risk for developing Eribulin-induced neuropathy, will allow the exclusion from these treatment of those patients harbouring the specific single nucleotide polymorphism (SNP). Given that Eribulin toxicity often results in treatment discontinuation, the ability to anticipate which patients will experience severe toxicity could allow for either early intervention or even possibly for prophylactic therapy, or for selection of the patients to be treated.

This study is primarily aimed at surveying the tolerability profile of Eribulin in an unselected population of patients with metastatic breast cancer in relation to toxicities already described in clinical trials, and neurotoxicity in particular.

The secondary objectives of this trial include:

* To study the relationship between specific genetic polymorphism and incidence and severity of peripheral neuropathy
* To describe treatment efficacy in terms of duration of treatment and impact on survival.

All toxicities will be collected and classified according to National Cancer Institute Common Terminology criteria for Adverse Events (NCI CTCAE) version 4.0 and monitored during all the treatment period and up to 30 days after therapy discontinuation.

In particular, evaluation of incidence and outcome of any grade AEs already recorded in previous clinical trials will be collected, as follows:

* asthenia/fatigue,
* neutropenia,
* alopecia,
* nausea,
* peripheral neuropathy
* constipation

Any other unexpected AEs shall be evaluated likewise.

Patients must be followed for AEs until every ongoing Eribulin-related/unrelated toxicity and AE have been resolved, or the Investigator assesses them as "chronic" or "stable" or until the end of the trial, whichever comes first. For patients who will begin a new anticancer therapy after the last study drug administration, the AEs reporting period will end at the time the new treatment starts.

For the determination of polymorphisms, a routine blood collection of two tubes with 3-5 ml of blood be performed. The sample can be collected at any time during the participant's first two treatment cycles. Blood will be collected in a Vacutainer containing ethylendiaminetetraacetic acid (EDTA). Immediately after blood collection, tubes have to be inverted (at least five times) and then stored at - 20° C.

PAINTER: Polymorphism And INcidence of Toxicity in ERibulin Treatment

Multicenter, Interventional, Single-arm, Phase IV Study Evaluating Tolerability of Eribulin and Its Relationship With a Set of Polymorphisms in an Unselected Population of Female Patients With Metastatic Breast Cancer

This is a kind of assessment to evaluate the quality of life of cancer patients during Eribulin treatment using unique measurements that share a common Unit of Measure

This is a kind of assessment to evaluate the quality of life during Eribulin treatment using unique measurements that share a common Unit of Measure

All toxicities and their grade will be reported according to Common Terminology criteria for Adverse Events (CTCAE) v4.0, especially the most common AEs reported in previous clinical studies (asthenia/fatigue, neutropenia, alopecia, nausea, peripheral neuropathy and constipation) but also other possible unexpected toxicities.

The association between a set of selected polymorphisms and the onset of all grades peripheral neuropathy will be investigated using blood samples collected at the time of treatment initiation.

Treatment tolerability will also be described in terms of dose intensity and dose schedule maintenance.

DOT will be calculated for each patient from the date of start of Eribulin treatment to the date of last Eribulin administration for any cause (i.e. progression of disease, unacceptable toxicity, patient refusal or physician decision).

OS will be calculated from the date of start of therapy to the date of death.

Oncologia Medica dell'Ospedale Fatebenefratelli

Digestive System Diseases

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Sorafenib

blood sample collection

Andrea Casadei-Gardini, MD

Sorafenib represents the standard care for advanced hepatocellular carcinoma (HCC). However, molecular predictors of sorafenib efficacy have not yet been identified.

The primary aim of the study is to validate the prognostic or predictive role of eNOS,Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to clinical outcome (progression-free survival, PFS) of HCC patients treated with sorafenib.

Sorafenib is a multikinase inhibitor acting on vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptor beta (PDGFRβ) involved in tumor cell proliferation and tumor angiogenesis.

Angiogenesis is a cascade of linked and sequential steps ultimately leading to tumour neovascularisation. Preclinical data suggested that significant HCC growth is dependent on angiogenesis, and an increase in tumour dimension may induce vascular endothelial cell proliferation.

Vascular endothelial growth factor (VEGF)-driven pathway has been demonstrated to play a major role in tumour angiogenesis. In fact, VEGF as a potent permeability factor promotes cell migration during invasion and as an endothelial growth factor stimulates endothelial cell proliferation, inducing the budding of new blood vessels around the growing tumour masses .

Single nucleotide polymorphisms (SNPs) in VEGF and VEGF receptor (VEGFR) genes have also been correlated to tumour neoangiogenesis through different biological mechanisms.

In the ALICE-1 study HCC patients receiving sorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 SNPs. At univariate analysis VEGF-A alleles C of rs25648, T of rs833061, C of rs699947, C of rs2010963, VEGF-C alleles T of rs4604006, G of rs664393, VEGFR-2 alleles C of rs2071559, C of rs2305948 were significant predictors of PFS and overall survival (OS). At multivariate analysis rs2010963, rs4604006 and Barcelona Clinic Liver Cancer (BCLC) stage resulted to be independent factors influencing PFS and OS.

In the ALICE-2 study SNPs of hypoxia inducible factor 1α (HIF-1α) were statistically significant for PFS and OS. The extended analysis of VEGF and VEGFR SNPs confirms the results of ALICE-1 study. The presence of GG genotype of rs12434438 (HIF-1α) select a population with a particularly poor outcome independently from the clinical effect of the two VEGF SNPs (PFS: 2.6 months, p\<0,0001; OS: 6.6 months, p\<0,0001).

In ePHAS study a training cohort of 41 HCC patients and a validation cohort of 87 patients receiving sorafenib was analyzed. At univariate analysis, patients homozygous for an endothelial nitric oxide synthase (eNOS) haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, p \<0.0001) and OS (3.2 vs.14.6 months, p = 0.024) than those with other haplotypes. These data were confirmed in the validation set in which patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, p \<0.0001) and OS (6.4 vs.18.0 months, p \< 0.0001).

On the basis of these premises this prospective study aims at validating the potential role of eNOS, VEGF, VEGFR, HIF-1 and Ang2 polymorphisms in patients with HCC treated with sorafenib.

Italian Study Of Validation Of Angiogenesis Polymorphisms In HCC Patients Treated With Sorafenib

Italian Multicentric Prospective Study Of Validation Of Angiogenesis Polymorphisms In HCC Patients Treated With Sorafenib

prognostic/predictive role of eNOS,Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to Progression Free Survival

prognostic/predictive role of eNOS,Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to Overall Survival

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Melanoma

Skin Neoplasms

Genetic Predisposition to Disease

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Neuroendocrine Tumor

Neuroepithelioma

The control group comprises patients with a first primary melanoma diagnosed in a twelve-month period.

Cases are patients diagnosed with a second or higher order primary in a six-year period.

Exposures of interest will be measured by a self-administered personal residence, occupation and vacation calendar, a telephone interview, and by testing DNA from buccal cells and blood, when available. Standardization of diagnosis will be undertaken by review of tissue slides. Questionnaire data will be completed by interviewers. DNA will be obtained from each individual in the form of 4-6 buccal swabs

Questionnaire

Exposures of interest will be measured by a self-administered personal residence, occupation and vacation calendar, a telephone interview, and by testing DNA from buccal cells and blood, when available. Standardization of diagnosis will be undertaken by review of tissue slides. Questionnaire data will be completed by interviewers. DNA will be obtained from each individual in the form of 4-6 buccal swabs.

Arlene Orlow, PhD

The goal of this study is to find out if some people are more likely to get melanoma, a form of skin cancer, than others are. To do this we will compare people who have had more than one melanoma to people who have had only one melanoma and to people who are similar but who have not developed melanoma.

People respond to the environment in different ways. Some may be born with genes that make them more likely to get this type of skin cancer. Each person has many ways to repair normal damage to their genes. Specific genes may affect the repair of sun damage. Other genes affect the way the skin itself reacts to the sun. We want to find out which genes have normal changes in them and lead to different responses to exposures, such as the sun. We also want to find out if sun habits are related to the way these genes work.

The purpose of this study is to better understand genetic susceptibility to melanoma and the interactions of specific polymorphisms with each other and with environmental factors.

To accomplish this, buccal swabs or blood specimens from patients with melanoma (either single primary or multiple primary) have been collected. Specimens will be prepared in the Epidemiology Laboratory at MSKCC. They will be analyzed at MSKCC for INK4A (and functional assays for DNA repair capacity when blood is available) and the melanocortin gene (MC1R), at the University of North Carolina for polymorphisms in DNA repair genes and immune function genes, at the University of Pennsylvania for polymorphisms in the melanocortin receptor gene (MC1R) and immune function genes, and at the University of California (Irvine) for polymorphisms in metabolizing genes (P450's and GST's). Samples will be banked at MSKCC and the University of New Mexico. In order to perform this study, subjects from population-based registries in the United States (New Jersey, North Carolina, Michigan, San Diego/Imperial Counties), Canada (Cancer Care Ontario, British Columbia), Italy (Turin), Australia (New South Wales, Tasmania), were interviewed, asked to provide blood or buccal swab samples and asked to provide permission to obtain and review slides of their primary melanoma. This study is now closed to accrual.

A Model for Genetic Susceptibility: Melanoma

University of New Mexico

University of North Carolina

University of Michigan

University of California, Irvine

New South Wales Cancer Control

University of Tasmania

Registro dei Tumori, Torino, Italy

British Columbia Cancer Agency

Cancer Care Ontario

University of Pennsylvania

Memorial Sloan Kettering Cancer Center

Glioma

Brain Neoplasms

Neoplasms, Neuroepithelial

Mitogens

This study will examine tissue from gliomas (a type of brain tumor) removed during surgery for gene mutations, or changes, thought to be involved in tumor formation and growth. One common gene mutation causes the receptor for a protein called epidermal growth factor (EGF) to be in an active state all of the time, allowing uncontrolled cell growth that can lead to tumor formation. This study will analyze blood and tumor tissue samples from patients with gliomas for:

* Changes in the EGF gene in the tumor
* Changes in other genes, such as that for the EGF receptor (EGFR)
* Changes in levels of EGF and EGFR, and in other proteins and genes that respond to changes in the levels of these proteins in the tumor
* Changes in the EGF gene and protein in the blood

The study will also determine if production of EGF and EGFR obtained from glioma and from blood cells derived from the tumor can be altered in the laboratory to grow indefinitely in culture.

Patients between 18 and 75 years of age with a brain tumor that requires surgical treatment may be eligible for this study.

Participants will be admitted to the NIH Clinical Center for about 3 to 10 days. They will have a physical and neurological examination, blood and urine tests, other tests, if medically necessary, and will be evaluated and prepared for surgery. During surgery, as much of the tumor as possible will be removed. A small amount of the tumor tissue will be collected for this study. No tissue will be removed for this study that would not otherwise have been removed. Some of the tissue will be used to culture glioma cells and the rest will be frozen and stored for examination, as described above. If any normal-appearing brain tissue is removed during surgery in order to enhance safety in removing the tumor, the normal tissue will be studied as well. Brain tissue that appears normal will not be removed strictly for research.

During surgery and the day after surgery, a blood sample will be drawn from a catheter (plastic tube) that was placed in an artery or vein for surgery. If catheters are no longer in place, blood will be drawn through a needle in a vein.

The epidermal growth factor (EGF) is an important biological mediator of normal growth and repair and is critical to epithelial tissue development and maturation of the central nervous system, among other functions. EGF is a natural focus of interest in cancer research because of its influence over mitogenesis, proliferation, and tumorigenesis. In addition, unregulated expression of its receptor, EGFR, has been identified as a common event in neoplastic transformation. In patients with the most malignant primary tumor of the brain, the glioblastoma multiforme (GBM), alterations in the EGFR or in its expression levels have been identified in approximately 50% of patients. We postulate that EGF-EGFR interactions may be important for the development, progression, and prognosis of human gliomas and that alterations of the EGF gene may predict the potential for glioma progression and the severity of disease.

Patients suspected of having, or with prior biopsy proof of, a WHO grade II-IV central nervous system (CNS) glial tumor(s) seen in the Surgical Neurology Branch, NINDS, will be considered for entry into this study. Tissue samples of tumor resected as part of standard care will be collected at surgery and preserved for research. Blood samples will also be collected. Blood will also be collected from anonymous normal volunteers who donate blood at the NIH Blood Bank; these anonymous donors will serve as controls.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Protocol to Examine Methylation of Tumor Suppression Genes in Women at High Risk of Developing Breast Cancer	NCT00323908	Breast Cancer		18 Years -	University of Kansas Medical Center
Susceptibility to Breast Cancer	NCT00004565	Breast Cancer Healthy		-	National Institutes of Health Clinical Center (CC)
Susceptibility to Breast Cancer	NCT00004565	Breast Cancer Healthy		-	National Institutes of Health Clinical Center (CC)
Tarceva Italian Lung Optimization tRial	NCT00637910	Non Small Cell ...	Erlotinib Docetaxel	18 Years -	Fatebenefratelli and Ophthalmic Hospital
PAINTER: Polymorphism And INcidence of Toxicity in ERibulin Treatment	NCT02864030	Metastatic Brea... Toxicity Neurotoxicity Drug Toxicity Adverse Drug Ev...	ERIBULIN MESYLA...	18 Years -	Oncologia Medica dell'Ospedale Fatebenefratelli
Italian Study Of Validation Of Angiogenesis Polymorphisms In HCC Patients Treated With Sorafenib	NCT02786342	Hepatocellular ...	blood sample co...	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Protocol to Examine Methylation of Tumor Suppression Genes in Women at High Risk of Developing Breast Cancer	NCT00323908	Breast Cancer		18 Years -	University of Kansas Medical Center
A Model for Genetic Susceptibility: Melanoma	NCT00591500	Melanoma Skin Cancer	Questionnaire Questionnaire	-	Memorial Sloan Kettering Cancer Center
The Role of Gene Changes in Brain Tumor Formation and Growth	NCT00059020	Glioma		-	National Institutes of Health Clinical Center (CC)
71A/G HSD17B5 SNP and Effects of Oral Contraceptive Pill in PCOS Women	NCT01372293	Polycystic Ovar...	oral contracept...	15 Years - 40 Years	Federal University of Rio Grande do Sul

Spots Global Cancer Trial Database for polymorphisms