Neoplasms

Nervous System Diseases

All Conditions

Rare Diseases

Esthesioneuroblastoma, Olfactory

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Olfactory Nerve Diseases

Cranial Nerve Diseases

Olfactory Neuroblastoma

Neuroepithelioma

Ricardo Carrau, MD

The purpose of this study is to collect and organize data into a repository to gather relevant information for future research from patients diagnosed with a rare malignant sinonasal cancer called esthesioneuroblastoma (ENB) and are scheduled to undergo endonasal skull base surgery. Data being collected includes surgical data, demographics, disease presentation, MRI, CT, PET imaging, and post-operative assessments including pathology tests. After surgery, the investigators will collect chemotherapy and radiation data. Participants will also complete quality of life questionnaires at their follow-up visits.

Esthesioneuroblastoma: Outcomes After Treatment

Anterior Skull Base (ASB); Skull Base Inventory (SBI); Multidimensional Disease Specific Inventory MDS; ASB-Nasal 12; Sino-Nasal Outcome Test (SNOT-20)

Ricardo L. Carrau, MD

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Squamous Cell

Nasopharyngeal Neoplasms

Thyroid Neoplasms

Thyroid Diseases

Head and Neck Neoplasms

Nasopharyngeal Carcinoma

Mouth Neoplasms

Oropharyngeal Neoplasms

Salivary Gland Neoplasms

Laryngeal Diseases

Laryngeal Neoplasms

Squamous Cell Carcinoma of Head and Neck

Endocrine System Diseases

Endocrine Gland Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Respiratory Tract Diseases

Mouth Diseases

Salivary Gland Diseases

Respiratory Tract Neoplasms

Oral Cancer

Laryngeal Cancer

Hypopharyngeal Cancer

Lip and Oral Cavity Cancer

The aim is to differentiate between patients with head and neck cancer from those without based on a blood sample.

The aim is to identify recurrence through serial monitoring patients with blood samples.

The intervention is a liquid biopsy as a blood sample taken in a peripheral vein. The blood samples are analyzed for cell free DNA, RNA and HPV-DNA

Liquid biopsy

Christian Grønhøj, MD, Ph.D

Christian Von Buchwald, MD, DMSc

This study investigates if head and neck squamous cell carcinoma can be tracked with cell-free tumor DNA, RNA or HPV-DNA, in blood samples from patients referred with suspicion of cancer, and if it can be used in detecting recurrence in patients already diagnosed and treated for head and neck squamous cell carcinoma.

Cell-free Tumor DNA in Head and Neck Cancer Patients

Cell-free Tumor DNAand HPV-DNA in Blood Samples From Newly Diagnosed Patients With Head and Neck Cancer

The primary outcome is to measure the percentage of head and neck squamous cell carcinomas that can be detected using a liquid biopsy (blood sample)

The primary outcome is to measure the percentage of recurrence in head and neck cancer patients through serial monitoring with liquid biopsies (blood sample)

Copenhagen University Hospital, Denmark

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology

Christian von Buchwald

Clinical Professor

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Recurrence

Thoracic Neoplasms

Lung Diseases

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Pembrolizumab + de-escalating doses of valemetostat

RP2D of valemetostat in combination with pembrolizumab

Phase Ib: Pembrolizumab 200mg will be administered by IV infusion every 3 weeks.

Phase II: Pembrolizumab 200mg will be administered by IV infusion every 3 weeks.

pembrolizumab

Phase Ib: Valemetostat will be given orally every day of every cycle (DL-1: 100mg, DL1: 150mg, DL2: 200mg).

Phase II: Valemetostat will be given orally daily at the recommended phase 2 dose.

valemetostat

Christine A Feierabend

Vassiliki Saloura, M.D.

National Cancer Institute Referral Office

Background:

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. These cancers have different causes, with smoking/tobacco exposure and human papilloma virus infection being the most common. . When HNSCC occurs in people who are not infected with HPV, the cancers are more likely to return after treatment; when this happens, overall survival is only about 10 months, thus better treatments are needed.

Objective:

To test a combination treatment using 2 drugs (valemetostat and pembrolizumab) in people with HNSCC. Phase 1b of the study will determine a recommended dose of the 2 drugs and evaluate how safe the combination is.; this will include patients with HPV-positive and HPV-negative HNSCC, as well as squamous cell NSCLC that have progressed on anti-PD-1/anti-PD-L1 therapies.Phase II will determine how effective the combination is and will focus on patients with HPV-negative HNSCC.

Eligibility:

People aged 18 years and older with HPV-negative HNSCC, sinonasal carcinoma of the head and neck, or squamous non-small cell lung cancer (NSCLC).

Design:

Participants will be screened. They will have a physical exam. They will have blood and urine tests and tests of their heart function. They will have imaging scans. They may have a biopsy: A small sample of tissue will be removed from the tumor.

Treatment will be given in 21-day cycles.

Pembrolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will receive pembrolizumab on the first day of each cycle.

Valemetostat is a tablet taken by mouth. Participants will take the tablet once a day at home. They will record the date and time of each dose in a diary. They will also write down any adverse effects they experience.

Participants may remain in the study up to 2 years.

Background:

* Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide, with approximately 60,000 patients diagnosed annually in the United States.
* Only 14% of HNSCC patients have structural defects in the genes encoding for the human leukocyte antigens (HLA) class I components, while a higher percentage of these tumors show downregulation of HLA class I components by immunohistochemistry supports those epigenetic mechanisms may be involved in the deregulation of these genes.
* Valemetostat (DS-3201) is an enhancer of zeste homolog 1 and 2 (EZH1/2) dual inhibitor that is actively being investigated in phase I and II trials for hematologic malignancies and is approved for adult T-cell leukemia/lymphoma (ATL) indication in Japan.
* Patients with recurrent or metastatic (R/M) pembrolizumab-na(SqrRoot) ve human papillomavirus (HPV)-negative HNSCC have a low 6-month progression-free survival (PFS) (28%) with pembrolizumab monotherapy, thus novel interventions are needed to increase the efficacy of pembrolizumab.

Objectives:

Phase Ib:

* To determine the recommended phase II dose (RP2D) of valemetostat in combination with pembrolizumab.
* To evaluate the safety of valemetostat in combination with pembrolizumab.

Phase II:

-To determine the disease control rate (DCR)=partial response (PR) + complete response (CR) + stable disease (SD).

Eligibility:

-Participants must have a diagnosis of locoregionally recurrent or metastatic (R/M) HPVnegative (Phase Ib and Phase II) or positive HNSCC (Phase Ib only): oral cavity, tonsil, pharynx, hypopharynx, larynx. Note: Nasopharyngeal carcinoma and cutaneous squamous cell carcinoma (SCC) are excluded

OR

(R/M) squamous non-small cell lung cancer (NSCLC) (Phase Ib only)

OR

(R/M) sinonasal carcinomas of the head and neck (Phase Ib only).

* Age \>18 years.
* Adequate organ and marrow function.

Design:

* This is an open-label multicenter phase Ib/II study to evaluate the safety and efficacy of the combined treatment of valemetostat and pembrolizumab.
* During phase Ib we will estimate the RP2D of the valemetostat in combination with pembrolizumab.
* During phase II we will examine the efficacy and continue to evaluate the safety of the study regimen at the RP2D of the valemetostat in combination with pembrolizumab.
* Participants will receive treatment in cycles consisting of 21 (+/- 3) days for 2 years.

Study of Front Line Pembrolizumab and Valemetostat in PD-L1 Positive, HPV-Negative Recurrent/Metastatic Squamous Cell Carcinoma (SCC) of the Head and Neck: The PANTHERAS

A Phase Ib/II Multicenter Study of Front Line Pembrolizumab and Valemetostat in PD-L1 Positive, HPV-Negative Recurrent/Metastatic Squamous Cell Carcinoma (SCC) of the Head and Neck: The PANTHERAS

.All IPD recorded in the medical record will be shared with intramural investigators upon request. 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. All collected IPD will be shared with collaborators under the terms of collaborative agreements.

Best confirmed response in participants with PD-L1 positive (CPS \>=1), HPV-negative relapsing/metatstic HNSCC treated with valemetostat and pembrolizumab compared to historical controls with pembrolizumab alone, by CT scan and brain MRI (PR+CR+SD)

Any toxicities that occur during timeframe.

Number of dose limiting toxicities (DLTs) that occur within the DLT period will determine RP2D.

Valemetostat level in blood samples collected for PK analysis

Participants will be assessed for survival while on study therapy and every 9 weeks before progression / every 6 weeks after progression.

Participants will be assessed for survival at 6 months after start of study, or until progression.

Participants will be assessed for survival until progression or 2 years after treatment start.

Stable disease \>= 6 months + complete response + partial response

ORR will be evaluated with periodic CT imaging.

Any toxicities identified during evaluation timeframe.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Esthesioneuroblastoma: Outcomes After Treatment	NCT02580136	Esthesioneurobl...		10 Years - 80 Years	Ohio State University
Esthesioneuroblastoma: Outcomes After Treatment	NCT02580136	Esthesioneurobl...		10 Years - 80 Years	Ohio State University
Cell-free Tumor DNA in Head and Neck Cancer Patients	NCT03942380	Head and Neck C... Head and Neck N... Head and Neck S... Oropharynx Canc... Oropharynx Neop... Oropharynx Carc... Oral Cavity Can... Oral Cancer Oral Neoplasm Larynx Cancer Larynx Carcinom... Larynx Neoplasm Nasopharyngeal ... Nasopharyngeal ... Nasopharynx Neo... Hypopharynx Can... Hypopharynx Neo... Hypopharynx Car... Sinonasal Carci... Thyroid Carcino... Thyroid Cancer Thyroid Neoplas... Salivary Gland ... Salivary Gland ... Salivary Gland ... Sinonasal Cance... Sinonasal Neopl...	Liquid biopsy	18 Years -	Rigshospitalet, Denmark
Study of Front Line Pembrolizumab and Valemetostat in PD-L1 Positive, HPV-Negative Recurrent/Metastatic Squamous Cell Carcinoma (SCC) of the Head and Neck: The PANTHERAS	NCT05879484	Sinonasal Cance... Squamous Non-sm... Lung Cancer Head and Neck S... Head and Neck C... Head and Neck C...	pembrolizumab valemetostat	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Cell-free Tumor DNA in Head and Neck Cancer Patients	NCT03942380	Head and Neck C... Head and Neck N... Head and Neck S... Oropharynx Canc... Oropharynx Neop... Oropharynx Carc... Oral Cavity Can... Oral Cancer Oral Neoplasm Larynx Cancer Larynx Carcinom... Larynx Neoplasm Nasopharyngeal ... Nasopharyngeal ... Nasopharynx Neo... Hypopharynx Can... Hypopharynx Neo... Hypopharynx Car... Sinonasal Carci... Thyroid Carcino... Thyroid Cancer Thyroid Neoplas... Salivary Gland ... Salivary Gland ... Salivary Gland ... Sinonasal Cance... Sinonasal Neopl...	Liquid biopsy	18 Years -	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for sinonasal cancer