Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Those who will receive targeted therapy based on their genetic profiling

Genetic profiling

Brian Leyland-Jones, MD

The primary objective is to examine the impact on progression-free survival of targeted therapy for breast cancer suggested by proteomic and genomic profiling.

To explore the impact of targeted therapy for breast cancer suggested by proteomic and genomic profiling using RPMA, targeted resequencing, IHC analysis, WGS, RNA-seq, and Exome sequencing on progression-free survival. When a molecular target cannot be identified, the patient will be treated with a therapy selected on an empirical basis by the investigator/treating physician at the individual site and will be followed for survival status. Only available, FDA-approved agents will be used.

Genomic and Proteomic Profiling Targets Influenced Treatment in Metastatic Breast Cancer

A Two Arm Pilot Study Utilizing Molecular Profiling to Find Potential Targets and Influence Treatments for Patients With Metastatic Breast Cancer or Advanced Gynecological Malignancies

Progression-free survival will be defined as the interval between the first dose of therapy and the occurrence of disease progression (fatal or non-fatal). Disease status will be assessed every 7 +/- 1 week until progression or time of treatment discontinuation, whichever is later. If progression is not observed at the end of therapy, patients will be assessed every 3 months until progression or further anti-cancer therapy.

Radiographic response will be evaluated according to RECIST 1.1 criteria in all patients with measurable disease. All sites of disease must be evaluated using the baseline assessment methods. Confirmatory assessment of complete response or partial response must be performed no less than 4 weeks after the initial documentation of response.

Avera McKennan Hospital & University Health Center

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Pancreatic Neoplasms

Genetic Predisposition to Disease

Disease Susceptibility

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Familial Pancreatic Cancer

Subjects with familiarity with pancreatic cancer enrolled into the IRFARPC registry (NCT04095195) will be submitted to buccal swab for saliva-based genetic testing

41 pancreatic cancer predisposition genes will be tested through a saliva-based swab

Saliva swab testing

Erica Secchettin, PharmD

AISP Association

Salvatore Paiella, MD, PhD

The goal of the PROPH-ITA Study is to perform genetic testing in family members of pancreatic cancer patients who may have a genetic predisposition. The subjects belong to the Italian Registry of Families At Risk of Pancreatic Cancer (IRFARPC, #NCT04095195). This investigational study will assess the genetic background of subjects with familiarity with pancreatic cancer only.

Participants may accept to undergo genetic testing as part of the IRFARPC registry, through a saliva-swab-based 41-gene panel test.

Up to 3,000 participants will be enrolled in this study.

Familial Pancreatic Cancer PROPHilation Program in Italy

Standardised Genetic Profiling of Subjects Belonging to the Italian Multicenter Registry of Prospective Surveillance of Subjects at Genetic Risk of Pancreatic Cancer

Prevalence of genetic mutations over the total tested

Correlation between presence of predisposing mutation and prevalence of cancers

Correlation between presence of predisposing mutation and prevalence of cancers in the family

General and Pancreatic Surgery Unit, University of Verona

Fondazione Valsecchi

Associazione Oltre La Ricerca

Genomica srl

Associazione Italiana per lo Studio del Pancreas

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Colorectal Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Patients with Advanced colorectal cancer will be managed by initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up combining standard imaging and ctDNA analysis (subsequent MTBs at each radiological assessment)

Patients with Advanced colorectal cancer will be managedby initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up based on standard imaging.

Patients with Advanced non-small cell lung cancer will be managed by initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up combining standard imaging and ctDNA analysis (subsequent MTBs at each radiological assessment)

Patients with Advanced non-small cell lung cancer will be managed by initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up based on standard imaging.

Liquid biopsy will be performed at cycle 1 day 1 and cycle 2 day of each line of systemic treatment, at each tumor evaluation by Imaging and at confirmation of progression

Liquid biopsy

Antoine ITALIANO, MD, PhD

Simone MATHOULIN-PELISSIER, MD, PhD

Thomas GRELLETY, MD

Valérie COCHIN, MD

Cédric LECAILLE, MD

Jean-Philippe METGES, MD,PhD

Sylvestre LE MOULEC, MD

COPE is a biology driven protocol with 2 independent, multicentric, two-arm non-comparative randomized (2:1) phase II trials in 2 distinct populations: colorectal cancer patients and non-small-lung cancer patients.

For each phase II trial, patient will be randomized between two arms with two patients randomized in arm A for one patient randomized in arm B:

* Arm A (Experimental - initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up combining standard imaging and ctDNA analysis)
* Arm B (Standard - initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up based on standard imaging).

Primary tumor tissue, if accessible at all, does not always provide enough information to stratify individual patients to the most promising therapy. Re-analysis of metastatic lesions by needle biopsy is possible but invasive, and limited by the known intra-patient heterogeneity of individual lesions. These hurdles might be overcome by analyzing circulating tumor DNA (liquid biopsy), which in principle might reflect all subclones present at that specific time point and allow sequential monitoring of disease evolution.

Once tumor's genetic profiling is available, patients will be discussed within a multidisciplinary tumor board (MTB) which aims at discussing the genomic profiles and at providing a therapeutic decision for each patient. This MTB involves clinical oncologists, molecular biologists and clinical or biological project manager.

All the patients carrying an actionnable alteration will be proposed to receive a matched drug or to enter in a matched clinical trial depending on the possibility of inclusion at the time of molecular report.

the investigators hypothesize that implementing sequential circulating tumor DNA analysis can improve management of patients with advanced cancer and therefore their survival.

For each distinct population of patients with Advanced solid tumor (colorectal cancer and non-small-cell lung cancer), patients will be randomized between two arms:

Experimental procedure: initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up combining standard imaging and ctDNA analysis (subsequent MTBs at each radiological assessment).

Standard procedure: initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up based on standard imaging.

Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study

Circulating DNA to Improve Outcome of Oncology PatiEnt: A Randomized Study - COPE Study

Overall Survival (OS) is defined as the time interval between the date of randomization and the date of death (of any cause).

An actionable alteration is determined according to the molecular tumor board.

A profiling-based targeted therapy corresponds to a therapy targeting an actionable alteration

Institut Bergonié

Adenocarcinoma

Neoplasm Metastasis

Carcinoid Tumor

Appendiceal Neoplasms

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Cecal Neoplasms

Cecal Diseases

Adenocarcinoma of the Appendix

Neuroendocrine Tumor

Neuroepithelioma

Anti-Infective Agents

All Drugs and Chemicals

Formaldehyde

Individuals ages 18+ years with an appendix cancer diagnosis in the United States.

Individuals ages 18+ years with an appendix cancer diagnosis seen at Vanderbilt.

Biological parents of active GAP (Social and Vanderbilt) Study participants.

Collection of archived fixed-formalin, paraffin-embedded (FFPE) primary appendix tumor tissues that were previously removed

Retrospective tissue procurement

GAP Study Coordinator (Rebecca B.)

Andreana N Holowatyj, PhD, MSCI

The GAP Study is a prospective cohort study designed to comprehensively investigate genetic variations that may contribute to cancer development among individuals diagnosed with appendix/appendiceal cancer who are ages 18+ years.

The Genetics of Appendix Cancer (GAP) Study aims to analyze hereditary factors, tumor characteristics and clinical features/outcomes among adults diagnosed with appendix cancer and their biological parents. Patients are recruited at any time after a diagnosis of appendix cancer and followed for up to 6 years after study enrollment. This cohort is enriched by robust biospecimens and data collections.

Genetics of Appendix Cancer Study

Genetics of Appendix Cancer: The GAP Study

Andreana Holowatyj, PhD, MSCI

Sponsor Investigator

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Analgesics

Central Nervous System Depressants

Hematinics

Antineoplastic Agents

Amino Acids

Morphine

Liver Extracts

3-Iodobenzylguanidine

Ceritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

All participants with relapsed or refractory neuroblastoma will have a tumor biopsy to identify genetic mutations. There is no drug given in this arm of the trial.

Qualified participants whose tumors show certain mutations in the anaplastic lymphoma kinase (ALK) pathway (based on genetic sequencing results) will receive a combination therapy of ceritinib and ribociclib, to be administered orally in 28-day cycles.

Two different doses of ceritinib and three different doses of ribociclib will be evaluated. Once the investigators have identified the highest safe dose of both drugs that can be given at the same time, additional participants will be enrolled in the study at this dose level.

It is possible that if starting at a lower dose, participants may take a higher dose once that dose has been deemed safe.

Biopsy

Tumor tissue will be sent to Foundation Medicine laboratory for molecular profiling.

Next Generation Sequencing

Participants will undergo different types of scans to look at your tumor. These scans include CT (computerized tomography), MIBG (meta-iodobenzylguanidine) PET (positron emission tomography), and MRI (magnetic resonance imaging). Participants may have more than one type of scan.

Tumor Scans

Participants will have needles inserted through their hip bone to remove fluid from inside the bone marrow. This test determines if participants have tumor in the bone marrow.

Bone marrow Tests

The exam includes taking participant weight, height, blood pressure, heart rate and respiratory rate and performing a examination of the participants body. The investigators may also check the participants vision with an eye chart.

Physical Exam

Participants will have their eyes will be evaluated using different instruments. Participants will also be asked to read an eye chart. The exams will take about 15 minutes.

Eye Exam

Standard blood tests will be done to measure different types of blood cells, to measure the amount of certain substances, and tests to check how well liver and kidneys are working. When possible, the investigators will take blood from the participants central line. If this is not possible, the investigators will take blood from a vein in the participants arm. First, the investigators will put some cream on the skin so that drawing blood will not be painful. Then the investigators will put a thin needle into the vein to draw the blood.

Labs

If the participant is 11 years old or older or has already started having periods, the participant will be asked to take a pregnancy test before starting this study. The results will be shared with the participant but not with the participants' parent(s). We strongly encourage the participant to share the results with the parents. If the participant is found to be pregnant, the participant will not be able to continue participation in the study. About 1 teaspoon of blood (or urine if a urine test) will be needed.

Pregnancy Test

A team member will take the participant's medical history, along with a listing of any medications that are being taken. Throughout the study, participants will be asked to report if they think that anything bad has happened as a result of the study.

Interviews

This is a test of electrical activity of the heart. The investigators will put electrodes (sticky pads attached to wires) on the participant's chest, arms and legs. The electrocardiogram (ECG) will not be uncomfortable, but the participant will have to lie still. It does not hurt and takes about 15 minutes.

The participant will have an ultrasound of the heart taken to assess heart function. The investigators will put some gel on the skin and use a machine to take pictures of the heart.

Echocardiogram

Participants will take ribociclib once per day orally for Days 1-21 of a 28-day cycle.

Ribociclib

Participants will take ceritinib once per day orally for 28 days of a 28-day cycle.

Yael P Mossé, MD

John M Maris, MD

The purpose of this research study is to match genomic aberrations in tumor cells at time of relapse to rationally designed combinations of molecularly targeted agents. This study will be done in two parts:

Part I: Tumor will be accessed at study entry via a biopsy and subjected to deep sequencing to identify protocol-specified biomarkers for therapy assignment.

Part II: If the tumor contains a genetic change defined by the study as being actionable, and other criteria are met, participants will be assigned to therapy based upon the genetic changes identified in the tumor biopsy.

Next Generation Personalized Neuroblastoma Therapy

Next Generation Personalized Neuroblastoma Therapy (The NEPENTHE Trial)

The primary variable is the incidence of dose limiting toxicities (DLTs) during the first 28 days of therapy

Area under the plasma concentration time-curve from zero to the last measured concentration

To describe whether the assigned targeted therapy can mediate anti-tumor effects in subjects with relapsed or refractory high-risk neuroblastoma within the context of a phase 1/phase1b biomarker-driven trial. Percentage of patients with objective response will be according to the International Neuroblastoma Response Criteria.

Neuroblastomas undergo substantial mutational evolution during therapy, and relapsed disease is more likely to be driven by a targetable oncogenic pathway. Genomic alterations measured by next-generation sequencing at time of disease progression will be characterized and reported in a descriptive manner.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Genomic and Proteomic Profiling Targets Influenced Treatment in Metastatic Breast Cancer	NCT02470819	Metastatic Brea... Breast Tumor Advanced Gyneco...	Genetic profili...	18 Years -	Avera McKennan Hospital & University Health Center
Familial Pancreatic Cancer PROPHilation Program in Italy	NCT05724992	Candidates for ...	Saliva swab tes...	18 Years - 80 Years	Associazione Italiana per lo Studio del Pancreas
Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study	NCT04258137	Colorectal Canc... Non Small Cell ...	Liquid biopsy	18 Years -	Institut Bergonié
Genetics of Appendix Cancer Study	NCT05734430	Appendix Cancer Appendiceal Can... Appendiceal Neo... Appendiceal Muc... Appendiceal Ade... Appendiceal Car... Appendiceal Neo... Appendix Adenoc... Appendix Mucino... Appendix Tumor Appendix Cancer... Appendix NET Low-Grade Appen... High Grade Appe... High Grade Appe...	Genetic profili... Retrospective t...	18 Years -	Vanderbilt-Ingram Cancer Center
Next Generation Personalized Neuroblastoma Therapy	NCT02780128	Neuroblastoma Cancer	Biopsy Next Generation... Tumor Scans Bone marrow Tes... Physical Exam Eye Exam Labs Pregnancy Test Interviews ECG Echocardiogram Ribociclib Ceritinib	1 Year - 21 Years	Children's Hospital of Philadelphia
Genetics of Appendix Cancer Study	NCT05734430	Appendix Cancer Appendiceal Can... Appendiceal Neo... Appendiceal Muc... Appendiceal Ade... Appendiceal Car... Appendiceal Neo... Appendix Adenoc... Appendix Mucino... Appendix Tumor Appendix Cancer... Appendix NET Low-Grade Appen... High Grade Appe... High Grade Appe...	Genetic profili... Retrospective t...	18 Years -	Vanderbilt-Ingram Cancer Center
Familial Pancreatic Cancer PROPHilation Program in Italy	NCT05724992	Candidates for ...	Saliva swab tes...	18 Years - 80 Years	Associazione Italiana per lo Studio del Pancreas
Next Generation Personalized Neuroblastoma Therapy	NCT02780128	Neuroblastoma Cancer	Biopsy Next Generation... Tumor Scans Bone marrow Tes... Physical Exam Eye Exam Labs Pregnancy Test Interviews ECG Echocardiogram Ribociclib Ceritinib	1 Year - 21 Years	Children's Hospital of Philadelphia

Spots Global Cancer Trial Database for genetic profiling