Neoplasms

All Conditions

Symptoms and General Pathology

Infections

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Recurrence

Epstein-Barr Virus Infections

Virus Diseases

Nasopharyngeal Carcinoma

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Avelumab

Immunoglobulins

Antineoplastic Agents, Immunological

Avelumab 10mg/kg IV infusion on days 1 and 15 of 28-day cycle

Avelumab 10mg/kg IV on days 1 and 15 of each 28-day cycle. Treatment will be given until disease progression, unacceptable toxicity, investigator decision or patient withdrawal.

Assuntina Sacco, MD

The purpose of this study is to determine whether avelumab, an investigational antibody against programmed death-ligand (PD-L1), has an effect on recurrent nasopharyngeal cancer. Avelumab is designed to block the interaction between programmed cell death protein 1 (PD-1), a known immune checkpoint, and PD-L1. By blocking this interaction, the immune system may be stimulated, allowing it to more effectively recognize and attack the cancer.

This is a prospective, multi-center, open-label, single-arm phase II trial to evaluate the efficacy of Avelumab for patients with recurrent/metastatic, Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma.

Upon study entry, all patients will receive Avelumab 10 milligrams per kilogram (mg/kg) intravenously (IV) on days 1 and 15 of each 28-day cycle. Treatment will be given until disease progression, unacceptable toxicity, investigator decision or patient withdrawal. Dose interruptions may occur per pre-specified criteria for grade 3 or higher toxicity.

Avelumab for Recurrent/Metastatic Nasopharyngeal Cancer

An Open-label, Single-arm, Multi-institutional Phase II Trial of Avelumab for Recurrent, Metastatic Nasopharyngeal Carcinoma

Based on Response Evaluation Criteria in Solid Tumors (RECIST)

Pfizer

Assuntina Sacco, M.D.

Assistant Professor, Medicine

Avelumab 10mg/kg IV infusion on days 1 and 15 of 28-day cycle

Avelumab: Avelumab 10mg/kg IV on days 1 and 15 of each 28-day cycle. Treatment will be given until disease progression, unacceptable toxicity, investigator decision or patient withdrawal.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Dr. Assuntina Sacco

Overall Response Rate

Overall Study

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Esophageal Neoplasms

Cholangiocarcinoma

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Esophageal Cancer

Ovarian Cancer

Bile Duct Cancer

Ovarian Epithelial Cancer

Mitogens

Subjects with HCC, cholangiocarcinoma, or esophageal, nasopharyngeal, or serous ovarian cancers, regardless of FGF/FGFR alteration status.

Subjects with HCC with FGF19 amplification.

Subjects with HCC without FGF19 amplification.

Subjects with cholangiocarcinoma or esophageal, nasopharyngeal, or serous ovarian cancers (regardless of FGF/FGFR status), or other solid tumor malignancies with documented FGF19/FGFR4 alteration.

In Part 1, initial cohort dose of INCB062079 at the protocol-defined starting dose, with subsequent dose escalations based on protocol-specific criteria. The recommended dose(s) from Part 1 will be taken forward into Part 2 cohorts.

INCB062079

Luis F. Vinas, MD

The purpose of this study is to evaluate the safety and tolerability, and determine the maximum tolerated dose of INCB062079 in subjects with advanced hepatocellular carcinoma and other malignancies.

An Open-Label Safety and Tolerability Study of INCB062079 in Subjects With Advanced Hepatocellular Carcinoma and Other Malignancies

A Phase 1, Open-Label, Dose-Escalation and Expansion, Safety and Tolerability Study of INCB062079 in Subjects With Advanced Hepatocellular Carcinoma and Other Malignancies

An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a subject provides informed consent.

Subjects with hepatocellular carcinoma (HCC) will be evaluated via modified RECIST for HCC; subjects with other advanced malignancies will be evaluated using standard RECIST v1.1.

Defined as maximum observed plasma concentration.

Defined as time to maximum plasma concentration.

Defined as minimum observed plasma concentration during the dosing interval.

Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration.

Defined as the apparent plasma terminal phase disposition half-life.

A plasma sample will be collected during screening for possible analysis of FGFR4 pathway mutations using tumor circulating DNA.

Incyte Corporation

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Immunomodulating Agents

Patients enrolled in Arm A will receive IPI-549 40 mg by mouth daily for at least 14 days

40mg by mouth (PO) every day (QD) for at least 14 days

IPI-549

Debanjali Ghosh, MA

Elaine Eng

Ezra Cohen, MD

The purpose of this study is to investigate how effective the study drug IPI-549 is against types of cancers. IPI-549 is considered experimental because it is not approved by the US Food and Drug Administration (FDA) for the treatment of cancer.

Patients will be treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research purposes through core biopsies will be obtained prior to initiation of IPI-549 and at surgery.

This is a phase 2 window of opportunity trial in patients with locally advanced head and neck cancer. A key objective is to provide the first proof that macrophage phenotype switching can be accomplished in humans and lay the groundwork for future trials of this novel approach to immune therapy. Patients who are candidates for surgical resection will be enrolled and treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research purposes through core biopsies will be obtained prior to initiation of IPI-549 and at surgery.

The study team hypothesizes that mRNA signatures of immune response will be increased in IPI-549-treated patients. For the efficacy endpoints, RECISTv1.1 will be used.

Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

Phase 2 Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

To detect IPI-549-induced changes in PI3Kγ-regulated signatures of immune suppression.

Compare pre- vs. post-treatment tumor tissue

T cell receptor (TCR) sequencing at baseline, surgery, end of treatment or at time of disease progression.

To determine safety and tolerability of IPI-549 and change in tumor size in patients with locally advanced HNSCC

The V Foundation for Cancer Research

Ezra Cohen

Professor of Medicine

Anti-Infective Agents

Docetaxel

Cisplatin

Raltegravir Potassium

Tubulin Modulators

Antimitotic Agents

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Integrase Inhibitors

HIV Integrase Inhibitors

Enzyme Inhibitors

Cisplatin, intravenous, 30 mg/m2, days 2 and 16, 1 to 2 hours

Raltegravir, oral,400 mg, twice per day, days 1 through 5 or days 15 to 19

Part 2 (optional): Docetaxel, intravenous, 75 mg/M2, day 2, every 21 days, 3 to 6 cycles

Part 2 (optional): Cisplatin, intravenous, 75 mg/M2, day 2, every 21 days, 3 to 6 cycles

Part 2: (optional): Raltegavir, oral, 400 mg, twice per day, days 1 through 5, 3 to 6 cycles

raltegravir and cisplatin

Houman Fekrazad, MD

The proposed study is a first-in-human pilot of a novel anti-cancer strategy: Metnase inhibition to potentiate DNA damaging chemotherapy. The investigators will conduct serial tumor biopsies in subjects with HNSCC at three timepoints: baseline, after cisplatin, and after cisplatin-raltegravir. The investigators will investigate immunohistochemical expression changes of γH2AX, Chk2, and Annexin V, three biomarkers of DNA damage and apoptosis. The study is designed to identify an intermediate signal of the potentiation of cisplatin chemotherapy by raltegravir in HNSCC, which will justify a future phase I/II study.

Pilot Study of Raltegravir and Cisplatin in Squamous Cell Carcinoma of Head and Neck

A Pilot Study of Raltegravir and Cisplatin in Squamous Cell Carcinoma of the Head and Neck

Expression changes of three selected tumor biomarkers (DNA damage and apoptosis) will be measured at baseline, after cisplatin alone, and after raltegravir-cisplatin. Tumor biomarkers include pChk2, Annexin V, and metnase.

Preliminary clinical activity of the combination of raltegravir and cisplatin-based chemotherapy in HNSCC will be measured by RECIST criteria. Patients who elect participation in Part 2 will undergo tumor response assessment in accordance with RECIST 1.1 criteria after every 3 cycles of cisplatin-docetaxel-raltegravir. Response rate after 3 cycles will be reported as applicable.

Preliminary toxicity of the combination of raltegravir and cisplatin-based chemotherapy in HNSCC as measured by the grading system (0-4) of the NCI CTCAE v.4

Baseline Metnase expression in HNSCC.

Preliminary toxicity of the combination of raltegravir and cisplatin-based chemotherapy in HNSCC as measured by the grading system (0-4) of the NCI CTCAE v.4

Progression-free and overall survival duration will be measured from entry into the protocol, until death.

From biopsy materials, quantitative score generated by Aperio Scanning. Digital photomicrographs will be scored for frequency and intensity.

American Cancer Society, Inc.

New Mexico Cancer Care Alliance

Communicable Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Immunologic Factors

One injection at one of the following dose levels

Dose level I: 2x107/m2 Dose level II: 5x107/m2 Dose level III: 1x108/m2

EBV specific CTL Infusion

Anti CD45 monoclonal antibody

Stephen Gottschalk, MD

To determine the safety of the combination of CD45 monoclonal antibody (Mab) followed by intravenous injection of EBV specific CTL in patients with nasopharyngeal cancer.

To compare the expansion, persistence and anti-tumor effects of the EBV specific CTL given after CD45 Mab administration with that observed in our first study.

To obtain preliminary information on the safety and response to an extended dosage regimen of EBV-specific CTL in patients, who have stable disease or a partial response after the initial dose of EBV-specific CTL.

Three different doses of CTL will be evaluated: dose level I: 2 x 10e7/m2; dose level II: 5 x 10e7/m2; dose level III: 1 x 10e8/m2

Day 1 YTH 24/54 800ug/kg over 8 hr; Day 2 YTH 24/54 800ug/kg over 8 hr; Day 3 Rest; Day 4-6 CTL Infusion (provided CD45 Mab level \<100 ug/ml).

Generation of EBV-specific CTL

After consent on the separate procurement protocol for CTL preparation the patient will donate up to 60-70cc of peripheral blood. 10-20cc of this will be used for the establishment of an EBV transformed lymphoblastoid cell line (EBV-LCL) by infection with virus produced from the B95-8 master cell line. The EBV-LCLs will take approximately four to six weeks to establish. 30-40cc of peripheral blood will be used to generate EBV specific CTLs. The CTL line will be prepared by co-cultivation of the irradiated EBV-LCL with patient PBMC. After establishment, the CTL lines will be checked for identity, phenotype and microbiological culture and cryopreserved prior to administration according to SOPs. The antigen specificity of each CTL line will be determined in cytotoxicity assay and when possible with tetramer reagents.

CD45 monoclonal antibodies

Anti-CD45 is a combination in equal amounts (weight for volume) of two monoclonal antibodies that are directed to non-overlapping epitopes on human CD45. It is a purified, concentrated, and sterile gamma globulin, primarily monomeric IgG, produced from the supernatant of the two rat IgG2b hybridoma clones, YTH 24 and YTH 54. The hybridomas were produced as fusions between splenocytes from DA rats immunized with human leukocytes and the rat myeloma line Y3. The combination of the two MAbs exerts a synergistic effect in vitro on complement-mediated cytotoxicity of white cells and it has been demonstrated to clear almost all passenger leukocytes from donor kidneys before transplant. Anti-CD45 Mabs have been made under cGMP conditions at the Therapeutic Antibody Center at Oxford and at Baylor College of Medicine and will pass the safety tests required by the FDA.

Cell administration

Patients will be pre-medicated with Diphenhydramine 1mg/kg IV (max 50 mg) and Acetaminophen 10mg/kg po (max 650 mg). EBV specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. Outpatients may be treated in the clinic. Monitoring will be undertaken according to institutional standards for administration of blood products with the exception that the injection will be given by a physician. Anti-emetics in appropriate dosage for each patient will be prescribed as necessary. Patients will receive supportive care for acute or chronic toxicity, including blood components or antibiotics, and other intervention as appropriate.

Antibody administration

Patients will be pre-medicated with Diphenhydramine 1mg/kg IV (max 50 mg) and Acetaminophen 10mg/kg po (max 650 mg). 800ug/kg CD45 Mabs will be given as 2 daily intravenous infusions over 8 hours. The antibody aliquot to be infused will arrive in the treatment area hand-carried by the attending physician or appointed designate. The antibody aliquot will be diluted in minimal amounts of normal saline. The resulting solution is stable for 24 hours. The antibody solution is administered by a syringe pump in incremental doses, 0.2-0.8 mg in the first hour and up to 10 mg/hr thereafter, for a total infusion time of a maximum of 6 hrs. A registered nurse and a physician must be readily available.

EBV-Specific CTLs Following CD45 Antibody to Patients With Epstein-Barr Virus (EBV) + Nasopharyngeal Carcinoma (NPC)

Administration of EBV-Specific Cytotoxic T Lymphocytes Following CD45 Antibody to Patients With EBV Positive Nasopharyngeal Carcinoma

The Methodist Hospital Research Institute

Center for Cell and Gene Therapy, Baylor College of Medicine

Baylor College of Medicine

Associate Professor, Pediatrics Hematology Oncology

Nervous System Diseases

Skin and Connective Tissue Diseases

Eye Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Pituitary Diseases

Melanoma

Neuroendocrine Tumors

Glioma

Retinoblastoma

Sarcoma

Mesothelioma

Mesothelioma, Malignant

Osteosarcoma

Medulloblastoma

Neuroblastoma

Carcinoid Tumor

Rhabdomyosarcoma

Ocular Melanoma

Neuroendocrine Tumor

Soft Tissue Sarcoma

Malignant Mesothelioma

Pancreatic Neuroendocrine Tumor

Vasoconstrictor Agents

Respiratory System Agents

Hematinics

Epinephrine

Liver Extracts

Racepinephrine

Epinephryl borate

ENV-101 (taladegib) tablets, 200 mg once-daily in 28-day cycles

ENV-101 (taladegib) tablets, 300 mg once-daily in 28-day cycles

ENV-101 (taladegib)

Paul Frohna, M.D., Ph.D.

This study employs a 2-stage design that aims to evaluate the efficacy and safety of ENV- 101, a potent Hedgehog (Hh) pathway inhibitor, in patients with refractory advanced solid tumors characterized by loss of function (LOF) mutations in the Patched-1 (PTCH1) gene. Stage 1 of this study will enroll approximately 44 patients randomized between two dose levels. As appropriate, Stage 2 of the study will expand enrollment based on the results of Stage 1.

A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations

A Phase 2, Multi-Center Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations

ORR is comprised of Complete Response (CR) and Partial Response (PR), measured by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1), as determined by an independent review (confirmed CR or PR will be defined as a repeat assessment performed no less than 28 days after the criteria for response is first met).

Unacceptable toxicities = non-hematologic AEs \>= Grade 3 in severity, not including alopecia and fatigue.

Best overall response of confirmed CR or PR as determined by the treating Investigator using RECIST 1.1.

CBR = the proportion of patients who achieved CR, PR or stable disease as determined by the treating Investigator using RECIST 1.1.

OS = Number of months from initiation of study medication to the date of death due to any cause or last follow up.

DOR = the number of months from the start of CR or PR, whichever response is recorded first and subsequently confirmed, to the first date that recurrent or progressive disease is documented or death.

PFS = number of months from initiation of study medication to the earlier of disease progression or death due to any cause or last follow up.

Percentage change in inhibition of Gli1, a marker for inhibition of the Hedgehog pathway, in skin biopsies.

Measurement of trough concentration of study medication in blood at Baseline and the end of each 28-day treatment cycle

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Avelumab for Recurrent/Metastatic Nasopharyngeal Cancer	NCT02875613	Nasopharyngeal ...	Avelumab	18 Years -	University of California, San Diego
An Open-Label Safety and Tolerability Study of INCB062079 in Subjects With Advanced Hepatocellular Carcinoma and Other Malignancies	NCT03144661	Hepatocellular ... Cholangiocarcin... Esophageal Canc... Nasopharyngeal ... Ovarian Cancer Solid Tumors	INCB062079	18 Years -	Incyte Corporation
Avelumab for Recurrent/Metastatic Nasopharyngeal Cancer	NCT02875613	Nasopharyngeal ...	Avelumab	18 Years -	University of California, San Diego
Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma	NCT03795610	Head and Neck S... Head and Neck C... Head and Neck C... Head and Neck C... Head and Neck C... HPV-Related Car... HPV-Related Mal... HPV-Related Squ...	IPI-549	18 Years -	University of California, San Diego
Pilot Study of Raltegravir and Cisplatin in Squamous Cell Carcinoma of Head and Neck	NCT01275183	Head and Neck C...	raltegravir and...	18 Years -	New Mexico Cancer Care Alliance
An Open-Label Safety and Tolerability Study of INCB062079 in Subjects With Advanced Hepatocellular Carcinoma and Other Malignancies	NCT03144661	Hepatocellular ... Cholangiocarcin... Esophageal Canc... Nasopharyngeal ... Ovarian Cancer Solid Tumors	INCB062079	18 Years -	Incyte Corporation
EBV-Specific CTLs Following CD45 Antibody to Patients With Epstein-Barr Virus (EBV) + Nasopharyngeal Carcinoma (NPC)	NCT00078546	Nasopharyngeal ... EBV Infections	EBV specific CT... Anti CD45 monoc...	-	Baylor College of Medicine
A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations	NCT05199584	Solid Tumors Wi...	ENV-101 (talade...	18 Years -	Endeavor Biomedicines, Inc.
EBV-Specific CTLs Following CD45 Antibody to Patients With Epstein-Barr Virus (EBV) + Nasopharyngeal Carcinoma (NPC)	NCT00078546	Nasopharyngeal ... EBV Infections	EBV specific CT... Anti CD45 monoc...	-	Baylor College of Medicine

Spots Global Cancer Trial Database for nasopharyngeal