Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma

Adenocarcinoma

Adenocarcinoma in Situ

Adenocarcinoma, Bronchiolo-Alveolar

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Multifocal Tissue Banking

Marie Christine Aubry, MD

The investigators are doing this research to see if they can use small tissue samples or fluid to develop a test that will determine if the tissue samples are related or not related to each other. The test will use the patient's DNA, which is part of their unique genetic material that carries the instructions for the body's development and function. Cancer can result from changes in a person's genetic material that causes cells to divide in an uncontrolled way and, sometimes, to travel to other organs. Currently, researchers and doctors know some of the genetic changes that can cause cancer, but they do not know all of the genetic changes that can cause cancer.

A frequent clinical dilemma in lung cancer care is the management of multifocal lung cancers. The management decision is based on determining if multiple cancers represent true independent primary cancers or related metastasis. This determination is critical to the appropriate staging of the cancers and treatment. Indeed, this distinction represents the difference between aggressive local therapy with either surgery or radiation therapy for primary early stage lesions, or palliative chemotherapy or best supportive care with appropriate symptom management for advanced stage metastatic disease.

No existing pathologic or molecular test is currently capable of making the distinction between multiple independent lung primaries from metastatic disease with accuracy. The recent release of preliminary data from the NLST screening trial, suggesting survival benefit for screening high risk patients with CT scanning, will only increase the number of patients facing these treatment dilemmas. The research team has recently developed a test that allows this distinction with great accuracy. This test allows determination of lineage between two tumors using the identification of large genomic rearrangements using mate pair next generation sequencing (MP). The test has been developed using fresh frozen tissue from resected lung tumors and is currently being validated for a clinical test.

The investigators' goal is to develop the test using cytology and small biopsy specimens.

The patient will have some or all of the samples taken listed below:

* Blood sample of 10 ml (2 teaspoons).
* Up to two lung bronchoscopic or transbronchoscopic needle aspiration biopsies will be given to the research study during an already scheduled bronchoscopy. In addition at the time of the bronchoscopy a brushing or washing specimen could be collected for research.
* A piece of lung or lymph node tissue taken at the time of the CT guided lung or lymph node biopsy will be given to the research study.
* A piece of lung tumor tissue removed during surgery will be given to the research study.
* If pleural fluid is removed as part of the procedure(s) and there is any fluid left after what is needed for your clinical care, it will be given to the research study.
* DNA genome sequencing will be performed on the collected tissues, blood and fluid.

A Clinical Test for the Treatment of Multifocal Lung Cancers Using Genome Sequencing

A Clinical Test for the Treatment of Multifocal Lung Cancers Using Genome

Performance of the mate pair next generation sequencing lineage test on cytology and small biopsy specimens obtained as part of routine clinical practice, through either a bronchoscopic, CT-guided needle procedure, or lung resection as evidenced in receiving results from the sequencing.

Mayo Clinic

MD, Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Infections

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Uterine Cervical Neoplasms

Communicable Diseases

Papillomavirus Infections

Vaginal Neoplasms

Vulvar Neoplasms

Condylomata Acuminata

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Genital Diseases

Urogenital Diseases

Disease Attributes

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Vulvar Diseases

Carcinoma in Situ

Vaginal Diseases

Vaginal Cancer

Vulvar Cancer

All Drugs and Chemicals

Vaccines

Participants will receive a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6

9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine in a 0.5-mL intramuscular injection

9vHPV vaccine

Medical Director

This study will evaluate the safety and immunogenicity of V503 (GARDASIL™9, 9vHPV vaccine) administered to 9- to 26-year-old females and males in Vietnam. The study hypothesis states that V503 induces acceptable anti-human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion at 4 weeks postdose 3.

Safety and Immunogenicity Study of V503 (GARDASIL™9, 9vHPV Vaccine) Administered to 9- to 26-Year-Old Females and Males in Vietnam (V503-017)

A Phase III Open-label Safety and Immunogenicity Study of GARDASIL™9 Administered to 9- to 26-Year-Old Females and Males in Vietnam

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Seroconversion was defined as a participant who was anti-HPV seronegative at Day 1 and became seropositive at 4 weeks postdose 3 (Month 7). Anti-HPV antibodies were measured using a Competitive Luminex Immunoassay.

An adverse event (AE) was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study vaccine. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study vaccine or protocol-specified procedure was also an AE. The participant or the parent/guardian of the participant were to record the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 5 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, and swelling) was summarized.

An AE was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study vaccine. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study vaccine or protocol-specified procedure was also an AE. The only solicited systemic AE was in response to results of daily oral temperature assessments. The participant or the parent/guardian of the participant will be asked to record the participant's oral temperature in the evening after each study vaccination and daily for 4 days after each study vaccination on VRC. The percentage of participants that had an AE due to an elevated oral temperature \[(≥ 37.8 °C (100.0 °F)\] was summarized.

A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants that experience at least one SAE that was reported as at least possibly related to the study vaccine was summarized.

Anti-HPV Type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibodies are measured using a Competitive Luminex Immunoassay. Titers are reported in milli Merck units/mL (mMU/mL).

Anti-HPV Type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibodies are measured using a Competitive Luminex Immunoassay. Titers are reported in mMU/mL.

Merck Sharp & Dohme LLC

Population for All-cause mortality included all enrolled participants. Population for Non-serious adverse events and serious adverse events included all participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.

Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6

9vHPV Vaccine

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Clinical Trials Disclosure

Anti-HPV 6

Anti-HPV 11

Anti-HPV 16

Anti-HPV 18

Anti-HPV 31

Anti-HPV 33

Anti-HPV 45

Anti-HPV 52

Anti-HPV 58

All allocated participants who were seronegative to the appropriate HPV type at Day 1, received all 3 vaccinations with the correct dose within acceptable day ranges, provided a serum sample within 21 to 49 days postdose 3, and had no protocol deviations that could interfere with the evaluation of participant's immune response to 9vHPV vaccination.

Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7

All participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.

Percentage of Participants With a Solicited Injection-site Adverse Event

Percentage of Participants With a Solicited Systemic Adverse Event

Percentage of Participants With a Vaccine-related Serious Adverse Event

Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1

Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7

Participants received a single 0.5-mL intramuscular injection of the 9-valent human papillomavirus (9vHPV) vaccine at Day 1, Month 2, and Month 6

Overall Study

Adenocarcinoma of Lung

Lung Adenocarcinoma

Tissue collection at the time of surgery for genetic testing and blood sample for germ line DNA.

Multifocal Lung Adenocarcinoma

Dennis Wigle, MD, PhD

To gather preliminary safety and outcome data for the multimodality treatment of lung adenocarcinoma in the setting of multifocal BAC.

Lung bronchoalveolar carcinoma (BAC) or adenocarcinoma in situ (AIS) continues to represent a poorly understood clinical entity. A frequent clinical dilemma in lung cancer care is the management of a documented or suspected invasive adenocarcinoma in the setting of multifocal ground glass opacity (GGO) consistent with multifocal AIS. These patients are typically classified as stage IV disease, and treated with palliative chemotherapy. No existing pathologic or molecular test is currently capable of making the distinction between independent primary versus metastatic tumors, a distinction for which substantial treatment impact exists. Many treating physicians suspect that outcomes for this specific patient subgroup are better than norms for stage IV disease, as such patients are frequently node-negative and without distant metastases despite multiple lesions present. To address this issue, we will evaluate a multimodality treatment protocol using aggressive local and targeted systemic therapy for multifocal lung adenocarcinoma, incorporating information from tumor genome sequencing for individualized treatment planning. The results will have significant impact in advancing the biologic understanding and treatment approach for lung adenocarcinoma in the setting of multifocal AIS.

Treatment of Multifocal Lung Adenocarcinoma

A Clinical Pathway for the Treatment of Multifocal Lung Adenocarcinoma Using Genome Sequencing

Overall survival compared to survival for Stage IV NSCLC on NCCTG trials

Post-treatment Pulmonary Function measured by pulmonary function testing (spirometry)

MD, PhD

Carcinoma, Squamous Cell

Papilloma

Squamous Intraepithelial Lesions of the Cervix

Uterine Cervical Dysplasia

Atypical Squamous Cells of the Cervix

Neoplasms, Squamous Cell

Precancerous Conditions

Cervical Intraepithelial Neoplasia

Assessment reagent urine sample HPV-PCR test result Assessment reagent vaginal secretion sample HPV-PCR test result Comparative Methods NGS Nucleic Acid Sequencing Results

Assessment reagent urine sample HPV-PCR test result Assessment reagent vaginal secretion sample HPV-PCR test result ApprovedListed Reagent Cervical Sample HPV-PCR Test Result

Thin-layer liquid-based cytology (TCT) results panel Colposcopy results Tissue biopsy pathological diagnosis result

Cervical cancer seriously threatens women's health and HPV infection is the main cause of cervical cancer. Traditionally, Cervical cancer screening is based on cervical exfoliated cell samples collected by health care provider, which is labor consuming and the coverage and compliance are both relatively low in some areas. Non-invasive hrHPV self-sampling test appears to be more acceptable and may improve the HPV screening coverage. This study aims to evaluate the clinical performance of a newly developed urine/vaginal self-sampling hrHPV test in Cervical cancer screening.

This study is a prospective multi-center clinical trial in China. Eligible participants are cervical cancer screening population who meet the enrollment criterias. All the participants are required to provide urine and vaginal samples by self-sampling, as well as the cervical exfoliated cell samples (by HCP). Participants may undergo colposcopy examination depending on the test results, and they will be followed up for three years.

The high-risk human papillomavirus nucleic acid detection kit (PCR-fluorescent probe method) developed by New Horizon Co., Ltd . is suitable for in vitro qualitative detection of 14 types of high-risk HPV ( 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) nucleic acid.

The clinical performance of the self-sampling test will be assessed base on the following outcomes:

1. The sensitivity for detecting CIN2+
2. The specificity in non-CIN2+ population
3. The risk of developing CIN2+ in test positive cohort and test negative cohort
4. The accuracy of detecting hrHPV

Primary Cervical Cancer Screening by Self-sampling HPV Test

Calculate the positive coincidence rate, negative coincidence rate, total coincidence rate, and Kappa value of the comparison reagents and calculate the 95% confidence interval to verify the accuracy of detecting HPV infection.

The consistency of HPV detection of different sample types was analyzed, and the absolute risk value, relative risk value and 95% confidence interval of the development of ≥CIN2 in different primary screening types were calculated and used to verify the safety and effectiveness of the intended use of cervical cancer primary screening.

BeijingNewBiorayTechnologyCo.,Ltd.

Hangzhou Newhorizon Health Technology Co., Ltd.

Peking University People's Hospital

Chief physician

Participants received a 0.5-mL vaccination of V501 by intramuscular injection on Day 1, Month 2, and Month 6

HPV types 6, 11, 16, and 18 vaccine 0.5 mL by intramuscular injection at Day 1, Month 2, and Month 6

V501

This study evaluated the long-term safety of quadrivalent Human Papillomavirus (HPV) types 6, 11, 16, 18 vaccine and its effectiveness in the prevention of cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ, and cervical cancer related to HPV in Japanese women.

V501 Safety and Efficacy Study in Japanese Women Aged 16 to 26 Years (V501-110)

A Phase IV Open-Label, Descriptive Study to Evaluate the Safety and Effectiveness on the Incidence of HPV 6, 11, 16 and 18 Related CIN 2/3 or Worse of the Quadrivalent HPV (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) Vaccine in 16- to 26-Year-Old Japanese Women

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

The endpoint included pathology panel consensus diagnosis of CIN 2 or 3, adenocarcinoma in situ, invasive squamous cervical carcinoma, or invasive adenocarcinoma of the cervix, and HPV type 6, 11, 16, or 18 detected in an adjacent section from the same tissue block. The point estimates and exact 95% confidence intervals for incidence rate were based on the Poisson distribution.

Participants at risk included all who received at least 1 vaccination and had safety follow-up. One participant received vaccination but did not have safety follow-up.

Asian

Race/Ethnicity, Customized

Senior Vice President, Global Clinical Development

The population analyzed included participants who received the full vaccination series, had at least 1 visit after Month 7, had no general protocol violations, and were seronegative at Baseline and polymerase chain reaction-negative from Baseline through Month 7 for the relevant HPV type.

Combined Incidence of Cervical Intraepithelial Neoplasia (CIN) 2/3 or Worse Related to Human Papillomavirus (HPV) Type 6, 11, 16, or 18

CIN2 and above disease cases, including HSIL or (CIN2, CIN2-3, CIN3) cervical cancer.

includes other benign lesions such as inflammation, polyps, and HPV-negative cases without pathological diagnosis and no abnormalities in TCT.

Jianliu Wang, Chief physician

Chenchen Ren, Chief physician

Jingyan Xie, Chief physician

Cervical cancer is one of the most common tumors in women, which seriously threatens women's life quality and safety. Human papilloma virus (HPV) infection is the most common cause of cervical cancer. Traditional HPV testing is based on the cells sample shed from the cervix. Recent studies have shown that urine HPV detection can be used as a new HPV detection method. This study intends to include patients undergoing TCT /HPV test/colposcopy in the department of gynecological diseases of the hospital, and collect urine samples and cervical swab samples. Sanger sequencing and cervical swab HPV test results were compared to evaluate the accuracy and clinical validity of urine HPV test combined with clinical diagnosis results of cases.

The urine high-risk HPV detection reagent (PCR-fluorescent probe method) developed by Hangzhou Newhorizon Health Technology Co., Ltd. can qualitatively detect 14 high-risk HPV DNA in human urine samples, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and can detect HPV 16 and 18.

This test adopts the comparative clinical research method, by collecting urine samples and cervical swab samples from the same subject for HPV nucleic acid detection. Among them, urine samples were tested for high-risk HPV nucleic acid testing and Sanger sequencing, and cervical swab samples were tested with HPV testing kits for cervical swabs that have been on the market. Combined with the clinical diagnosis results of the cases, the performance of the urine HPV detection technology is compared and evaluated.

For patients undergoing TCT testing/HPV testing/colposcopy in the gynecological clinic or colposcopy clinic of the hospital, the subjects will be screened through the admission criteria and signed an informed consent; the examiner is required to collect cervical swab samples and, at the same time, issue urine collection When the tube is given to the subject, the subject must collect urine samples by themselves according to the sampling instructions or under the guidance of medical personnel; the patient samples will be tested by Hangzhou Newhorizon Health Technology Co., Ltd.; the clinical examination report will be collected as the case materials of this study.

Clinical Evaluation of Detection of High Risk HPV in Urine

Clinical Evaluation Study of Urine hrHPV Detection for the Diagnosis of Presence of Cervical HPV and Correlation of Cervical Lesions

Consistency analysis of urine HPV test and Sanger sequencing results/cervical swab HPV test results The main evaluation indicators are the total test positive coincidence rate, total test negative coincidence rate, total coincidence rate, 16/18/other 12 types of positive and negative coincidence rates, kappa value and 95% confidence interval.

Using the clinical diagnosis result (colposcopy or pathology report) of the case as the gold standard, evaluate the sensitivity, specificity and the corresponding 95% confidence interval, etc. of the HPV detection of urine samples and cervical swab samples for cervical intraepithelial neoplasia grade II and above (≥CIN2)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Clinical Test for the Treatment of Multifocal Lung Cancers Using Genome Sequencing	NCT02705404	Lung Neoplasms Carcinoma Non-s...	Multifocal Tiss...	18 Years -	Mayo Clinic
Safety and Immunogenicity Study of V503 (GARDASIL™9, 9vHPV Vaccine) Administered to 9- to 26-Year-Old Females and Males in Vietnam (V503-017)	NCT03546842	Papillomavirus ... Uterine Cervica... Vulvar Neoplasm... Vaginal Neoplas... Adenocarcinoma ... Condylomata Acu...	9vHPV vaccine	9 Years - 26 Years	Merck Sharp & Dohme LLC
Treatment of Multifocal Lung Adenocarcinoma	NCT01946100	Lung Neoplasms Carcinoma Non-s... Adenocarcinoma	Multifocal Lung...	18 Years -	Mayo Clinic
A Clinical Test for the Treatment of Multifocal Lung Cancers Using Genome Sequencing	NCT02705404	Lung Neoplasms Carcinoma Non-s...	Multifocal Tiss...	18 Years -	Mayo Clinic
Primary Cervical Cancer Screening by Self-sampling HPV Test	NCT05613283	Human Papilloma... Cervical Cancer Negative For In... Atypical Squamo... Atypical Squamo... Cervical Squamo... Low-Grade Squam... High-Grade Squa... Cervical Intrae... Cervical Intrae... Cervical Intrae... Atypical Glandu... Atypical Glandu... Atypical Glandu... Cervical Squamo... Adenocarcinoma ... Cervical Adenoc...		21 Years - 65 Years	Peking University People's Hospital
V501 Safety and Efficacy Study in Japanese Women Aged 16 to 26 Years (V501-110)	NCT01544478	Cervical Cancer Cervical Intrae... Adenocarcinoma ...	V501	16 Years - 26 Years	Merck Sharp & Dohme LLC
Safety and Immunogenicity Study of V503 (GARDASIL™9, 9vHPV Vaccine) Administered to 9- to 26-Year-Old Females and Males in Vietnam (V503-017)	NCT03546842	Papillomavirus ... Uterine Cervica... Vulvar Neoplasm... Vaginal Neoplas... Adenocarcinoma ... Condylomata Acu...	9vHPV vaccine	9 Years - 26 Years	Merck Sharp & Dohme LLC
A Clinical Test for the Treatment of Multifocal Lung Cancers Using Genome Sequencing	NCT02705404	Lung Neoplasms Carcinoma Non-s...	Multifocal Tiss...	18 Years -	Mayo Clinic
Clinical Evaluation of Detection of High Risk HPV in Urine	NCT05210348	Human Papilloma... Cervical Cancer Human Papilloma... Negative for In... Atypical Squamo... Cervical Squamo... Atypical Squamo... Low-grade Squam... High-Grade Squa... Cervical Intrae... Cervical Intrae... Cervical Intrae... Atypical Glandu... Atypical Glandu... Atypical Glandu... Cervical Squamo... Adenocarcinoma ... Cervical Adenoc...		20 Years - 65 Years	Peking University People's Hospital

Spots Global Cancer Trial Database for adenocarcinoma in situ