Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Musculoskeletal Diseases

Rare Diseases

Carcinoma

Nasopharyngeal Carcinoma

Paranasal Sinus Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Nose Neoplasms

Nose Diseases

Respiratory Tract Diseases

Paranasal Sinus Diseases

Respiratory Tract Neoplasms

Sinus Cancer

Herbal and Botanical

All Drugs and Chemicals

Eucalyptus

Clove

Patients undergo olfactory training by smelling 4 essential oils in vials (rose, lemon, clove, and eucalyptus) over 15 seconds each, twice daily for 12 weeks.

Patients undergo sham training by smelling canola oil in 4 vials over 15 seconds each, twice daily for 12 weeks.

Physiologic Testing

Quality-of-Life Assessment

Sham Intervention

Therapeutic Procedure

rose essential oil

lemon essential oil

clove essential oil

eucalyptus essential oil

canola oil placebo

Zara Patel

This randomized phase I trial studies how well olfactory training works in improving sense of smell after radiation therapy in patients with paranasal sinus or nasopharyngeal cancer. Olfactory training may improve smell function after radiation therapy in patients with paranasal sinus or nasopharyngeal cancer.

PRIMARY OBJECTIVES:

I. To evaluate the effect of olfactory training on olfactory function in patients with paranasal sinus and nasopharyngeal carcinoma suffering from olfactory loss after radiation.

SECONDARY OBJECTIVES:

I. To evaluate the possible effect of olfactory training on quality of life in patients with paranasal sinus and nasopharyngeal carcinoma suffering from olfactory loss after radiation.

II. To study rate and severity of olfactory dysfunction after radiation therapy in patients with paranasal sinus or nasopharyngeal carcinoma.

III. To evaluate the possible preventive effect of olfactory training on olfactory dysfunction in patients with paranasal sinus and nasopharyngeal carcinoma who will undergo radiation therapy.

OUTLINE: Patients are randomized to 1 of 2 arms. Arm I: Patients undergo olfactory training by smelling 4 essential oils in vials (rose, lemon, clove, and eucalyptus) over 15 seconds each, twice daily for 12 weeks.

Arm II: Patients undergo sham training by smelling canola oil in 4 vials over 15 seconds each, twice daily for 12 weeks.

Olfactory Training in Improving Sense of Smell After Radiation Therapy in Patients With Paranasal Sinus or Nasopharyngeal Cancer

Olfactory Training For Post Radiation Olfactory Loss In Patients With Paranasal Sinus and Nasopharyngeal Carcinoma

T-test or Mann-Whitney U test, where appropriate, will be used for comparing continuous variables, and chi-squared test will be used for comparing categorical variables. Continuous UPSIT score will be summarized using the following statistics: number of subjects, arithmetic mean, standard deviation, median, first quartile, third quartile, minimum, and maximum values. The dependent variable UPSIT score will be either the percent change from baseline or change from baseline in the endpoint. Mixed model repeated measures (MMRM) analysis will be used and the model will included fixed effect terms

Within each subgroup of participants, change in QOD score after olfactory training will be calculated and compared between treatment and control group. Confidence interval (CI) 95% and P value \< 5% will be set as statistical parameters to define if noted difference is significant. Based on previous studies, a change of \>= 1/2 standard deviation of the pre-treatment score would be clinically significant.

T-test or Mann-Whitney U test, where appropriate, will be used for comparing continuous variables, and chi-squared test will be used for comparing categorical variables. Continuous UPSIT score will be summarized using the following statistics: number of subjects, arithmetic mean, standard deviation, median, first quartile, third quartile, minimum, and maximum values. Continuous UPSIT score will be summarized using the following statistics: number of subjects, arithmetic mean, standard deviation, median, first quartile, third quartile, minimum, and maximum values. These statistics will be shown

Stanford University

Infections

Symptoms and General Pathology

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Antineoplastic Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Fluorouracil

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients receive PF regimen as in Arm I of Phase II.

Clinical Observation

Gemcitabine Hydrochloride

Intensity-Modulated Radiation Therapy

Laboratory Biomarker Analysis

Nancy Lee

There are two study questions we are asking in this randomized phase II/III trial based on a blood biomarker, Epstein Barr virus (EBV) deoxyribonucleic acid (DNA) for locoregionally advanced non-metastatic nasopharyngeal cancer. All patients will first undergo standard concurrent chemotherapy and radiation therapy. When this standard treatment is completed, if there is no detectable EBV DNA in their plasma, then patients are randomized to either standard adjuvant cisplatin and fluorouracil chemotherapy or observation. If there is still detectable levels of plasma EBV DNA, patients will be randomized to standard cisplatin and fluorouracil chemotherapy versus gemcitabine and paclitaxel. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, fluorouracil, gemcitabine hydrochloride, and paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cisplatin and fluorouracil is more effective than gemcitabine hydrochloride and paclitaxel after radiation therapy in treating patients with nasopharyngeal cancer.

PRIMARY OBJECTIVES:

I. To determine whether substituting adjuvant concurrent high dose cisplatin (CDDP) and fluorouracil (5-FU) with gemcitabine (gemcitabine hydrochloride) and paclitaxel will result in superior progression-free survival. (Detectable Plasma Epstein Barr Virus \[EBV\] Deoxyribonucleic Acid \[DNA\] Cohort randomized Phase II) II. To determine whether omitting adjuvant CDDP and 5-FU (observation alone in the adjuvant setting) will result in non-inferior overall survival as compared with those patients receiving adjuvant CDDP and 5-FU chemotherapy. (Undetectable Plasma EBV DNA Cohort Phase III)

SECONDARY OBJECTIVES:

I. Time to distant metastasis. (Randomized Phase II and Phase III) II. Time to local progression. (Randomized Phase II and Phase III) III. Time to regional progression. (Randomized Phase II and Phase III) IV. Progression-free survival (Undetectable Cohort). V. Overall survival (Detectable Cohort). VI. Acute and late toxicity profiles based on clinician-reported Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 4. (Randomized Phase II and Phase III) VII. Death during or within 30 days of end of protocol treatment. (Randomized Phase II and Phase III) VIII. Quality of life (general and physical well-being). (Randomized Phase II and Phase III) IX. Quality of life (hearing). (Randomized Phase II and Phase III) X. Quality of life (peripheral neuropathy). (Randomized Phase II and Phase III) XI. Cost effectiveness. (Randomized Phase II and Phase III)

OUTLINE:

Patients undergo intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6.5 weeks and receive low-dose cisplatin intravenously (IV) over 30-60 minutes once weekly during IMRT. Beginning 1 week after chemoradiation, plasma samples are collected for EBV DNA analysis.

PHASE II: Patients with detectable EBV DNA from pre-treatment analysis are randomized to 1 of 2 treatment arms.

ARM I: Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

PHASE III:

Patients with undetectable EBV DNA from pre-treatment analysis are randomized to 1 of 2 treatment arms.

ARM III: Patients receive PF regimen as in Arm I.

ARM IV: Patients undergo clinical observation.

After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA

Randomized Phase II and Phase III Studies of Individualized Treatment for Nasopharyngeal Carcinoma Based on Biomarker Epstein Barr Virus (EBV) Deoxyribonucleic Acid (DNA)

Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test. The confidence interval approach will be used for the final analysis of OS.

Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test. A one-sided log rank test will be used to compare the PFS at a significance level of 0.1379.

Correlation between categorical measures will be summarized by odds ratios, chi-square tests, and associated measures. Adjusted correlation may be derived from analysis of covariance (ANCOVA) models or derived directly using nonparametric analysis of variance (ANOVA) models if normality assumption is violated. Correlations between HHIE-S PRO scores and PTA and FACT-NP hearing, and PTA will be compared as dependent statistics

QOL analysis including overall score and change from baseline will be summarized using mean and standard deviation at each time point for each arm. Overall and nasopharyngeal-specific QOL, hearing QOL (FACT-NP hearing domain, HHIE-S scores), peripheral neuropathy QOL over the short and long term and pure-tone audiometry (PTA) scores will be compared using a two sample independent t test and paired t test if the comparison is within the experimental arm between different time points.

Changes in patient reported outcome (PRO) scores will be correlated to clearance or non-clearance of EBV titers. Descriptive statistics derived from FACT-NP will be used to enrich the understanding of QOL as it pertains to the 2 phase III arms of observation versus additional adjuvant chemotherapy. Univariable and multivariable analysis will be performed using the Cox proportional hazards model for OS and distant metastasis. Pearson correlation will be estimated between general and physical well-being. QOL measures and change from baseline will be correlated to EBV DNA.

Incremental cost effectiveness ratios will be compared to determine the probability of cost effectiveness of various interventions, with sensitivity analyses to identify model weaknesses. The expected value of perfect information will be determined to delimit the upper boundary for cost-effective future investment in this area of research.

Rates of specific acute toxicity profiles and late toxicity profiles will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test between the 2 treatment arms.

Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a 1-sided log rank test.

The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.

Defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. The cumulative incidence method will be used to estimate local, regional, and distant failure rates. The failure rates for the experimental treatment will be compared against the control using a failure-specific log-rank test. Multivariate analysis will be performed using the Cox proportional hazards model.

National Cancer Institute (NCI)

NRG Oncology

Recurrence

Disease Attributes

Antibodies

Durvalumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antibodies, Monoclonal

Antineoplastic Agents, Immunological

Patients receive durvalumab intravenously (IV) over 1 hour on day 1 and epacadostat orally (PO) twice a day (BID) on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients with disease progression who are benefiting from treatment in the opinion of the principal investigator may continue durvalumab and epacadostat for up to an additional 12 months from the initiation (or re-initiation) of treatment on study.

Epacadostat

Alain P Algazi, MD

This phase II trial studies how well durvalumab and epacadostat work in treating patients with Epstein-Barr virus positive nasopharyngeal cancer that cannot be removed by surgery (unresectable), has come back (recurrent), or has spread to other places in the body (metastatic). Epacadostat blocks the enzyme, IDO1, from working. Blocking this enzyme may allow for a stronger immune response against cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving durvalumab and epacadostat may work better in treating patients with nasopharyngeal cancer compared to durvalumab alone.

PRIMARY OBJECTIVE:

I. Determine whether adding an IDO inhibitor to PD-L1 antibody therapy improves the probability of remission in nasopharyngeal carcinoma (NPC).

SECONDARY OBJECTIVES:

I. Determine whether adding an IDO inhibitor to PD-L1 antibody therapy improves long-term clinical outcomes in NPC.

II. Determine whether the combination of durvalumab and epacadostat in recurrent and metastatic NPC patients is safe and well tolerated.

EXPLORATORY OBJECTIVES:

I. Identify potential associations between pre-treatment and on-treatment regulatory and effector immune cell populations and clinical outcomes in NPC patients treated with durvalumab and epacadostat.

II. Characterize the oral and fecal microbiome in responding and non-responding patients.

OUTLINE:

Patients receive durvalumab intravenously (IV) over 1 hour on day 1 and epacadostat orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients with disease progression who are benefiting from treatment in the opinion of the principal investigator may continue durvalumab and epacadostat for up to an additional 12 months from the initiation (or re-initiation) of treatment on study.

After completion of study treatment, patients are followed up every 3 months until start of a new anti-cancer treatment, until 30 days after documented disease progression, until death, or until 36 months from the initiation of treatment on study, whichever comes first.

Durvalumab and Epacadostat for Treatment of Unresectable, Recurrent, or Metastatic Epstein-Barr Virus Positive Nasopharyngeal Cancer

A Multi-Center, Phase II, Open Label, Single-Arm Trial of Durvalumab and Epacadostat in Patients With Unresectable, Recurrent, and Metastatic EBV+ NPC

Patients will meet the primary endpoint (BORR) if they attain a confirmed complete response (CR) or partial response (PR) with the combination treatment with a 4-week confirmatory scan. All response data will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The point estimate and two-sided exact binomial 95% confidence interval for the objective response rate will be provided.

Progression free survival (PFS) is defined as the number of days from enrollment to progression (for subjects who have progression) and the number of days from enrollment to last assessment (for subjects who do not have progression). The distributions of PFS will be summarized using the Kaplan-Meier method. Estimates of the median PFS will also be provided.

Overall survival (OS) defined as the number of days from enrollment to death, or from enrollment to date last known alive. The distributions of OS will be summarized using the Kaplan-Meier method. Estimates of the median OS will also be provided.

Duration of response (DoR) is defined as the time (in days) from randomization to progression (or death from any cause) in patients who had a best overall response of complete response (CR) or partial response (PR). The distributions of DoR will be summarized using the Kaplan-Meier method. Estimates of the median DoR will also be provided.

Biochemical Response to Treatment will be obtained by measuring the metabolic response of the IDO1 enzyme (Trp/Kyn levels). Levels of tryptophan and kynurenine will be evaluated by liquid chromatography with tandem mass spectrometry to monitor systemic activity in modulating the IDO1 enzyme

Biochemically verified drug efficacy will be obtained by measuring the metabolic response of the IDO1 enzyme (Trp/Kyn levels). Levels of tryptophan and kynurenine will be evaluated by liquid chromatography with tandem mass spectrometry to monitor systemic activity in modulating the IDO1 enzyme

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Olfactory Training in Improving Sense of Smell After Radiation Therapy in Patients With Paranasal Sinus or Nasopharyngeal Cancer	NCT03049358	Stage 0 Nasopha... Stage 0 Paranas... Stage I Nasopha... Stage I Paranas... Stage II Nasoph... Stage II Parana... Stage IIA Nasop... Stage IIB Nasop... Stage III Nasop... Stage III Paran... Stage IV Nasoph... Stage IV Parana... Stage IVA Nasop... Stage IVA Paran... Stage IVB Nasop... Stage IVB Paran... Stage IVC Nasop... Stage IVC Paran...	Physiologic Tes... Quality-of-Life... Sham Interventi... Therapeutic Pro... rose essential ... lemon essential... clove essential... eucalyptus esse... canola oil plac...	19 Years -	Stanford University
Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA	NCT02135042	Epstein-Barr Vi... Stage II Nasoph... Stage III Nasop... Stage IVA Nasop... Stage IVB Nasop...	Cisplatin Clinical Observ... Fluorouracil Gemcitabine Hyd... Intensity-Modul... Laboratory Biom... Paclitaxel Quality-of-Life...	18 Years -	NRG Oncology
Durvalumab and Epacadostat for Treatment of Unresectable, Recurrent, or Metastatic Epstein-Barr Virus Positive Nasopharyngeal Cancer	NCT04231864	Epstein-Barr Vi... Metastatic Naso... Recurrent Nasop... Stage III Nasop... Stage IV Nasoph... Stage IVA Nasop... Stage IVB Nasop...	Durvalumab Epacadostat	18 Years -	University of California, San Francisco
Durvalumab and Epacadostat for Treatment of Unresectable, Recurrent, or Metastatic Epstein-Barr Virus Positive Nasopharyngeal Cancer	NCT04231864	Epstein-Barr Vi... Metastatic Naso... Recurrent Nasop... Stage III Nasop... Stage IV Nasoph... Stage IVA Nasop... Stage IVB Nasop...	Durvalumab Epacadostat	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for stage ivb nasopharyngeal carcinoma