patients will be recruited from the outpatient's viral hepatitis clinic- Kasr-Eleiny hospital
The patients will be diagnosed as HCV positive through (antiHCV-Ab) and (HCV-PCR) tests

healthy volunteers recruited from the outpatient clinic of the Faculty of Dentistry- Cairo University

Hepatitis C Viral

Oral swab from the buccal mucosa will be obtained and then analysed Oral Microbiome analysis:The microbial RNA will be sequenced using Next Generation Sequencer.

Oral microbiome analysis

Oral Microbiome of Patients With Hepatitis C Virus Infection

Oral Microbiome of Patients With Chronic Hepatitis C Virus Infection: A Case-Control Study

changes in oral microbial composition will be analysed using bioinformatics tools to provide figures showing the extent of dysbiosis and its composition

Ayat Gamal-AbdelNaser

Principal investigator

Cairo University

In three combined drugs used in nasopharyngeal carcinoma, the valproic acid and valganciclovir administration will be followed by indication to find the maximum tolerance dose of gemcitabine.

Nasopharyngeal Carcinoma

Gemcitabine will be administrated 600~1250 mg/m^2 intravenously according to the body surface area at day 1 and day 8 in a 28 day-treatment cycle. The treatment cycle of 28 days will be repeated maximum 6 times. The first dose level of gemcitabine will be started at 800 mg/m^2. If no subject suffered the dose limit toxicity, 1000 mg/m^2 and even 1250 mg/m^2 will be started by order. If subjects suffered the dose limit toxicity in 800 mg/m^2, the 600 mg/m^2 will be started.

Gemcitabine

Valproic acid will be administrated orally by the fixed dose 12.5 mg/kg/day according to instructions from day 1 to day 14 in one treatment cycle. The treatment cycle of 28 days will be repeated maximum 6 times.

Valproic acid

Valganciclovir will be administrated orally by the fixed dose 1350 mg/day (creatinine clearance rate ≥ 60 mL/min) or 900 mg/day (creatinine clearance rate ≥ 40 mL/min and < 60 mL/min) from day 9 to day 15 in one treatment cycle. The treatment cycle of 28 days will be repeated maximum 6 times.

Valganciclovir

Chang-Gung Memorial Hospital, Linkou

Study of Cytolytic Viral Activation Therapy (CVAT) for Recurrent/Metastatic Nasopharyngeal Carcinoma

Phase I Study of Cytolytic Viral Activation Therapy (CVAT) for Recurrent/Metastatic Nasopharyngeal Carcinoma

According to Worst Toxicity CTCAE v4.03 Grade and FDA indication of gemcitabine, the dose limiting toxicity (DLT) of this trial was determined in the first treatment cycle and DLTs were defined as ≥1 of the following effects attributable to the study drug and requiring discontinuation or a significant dose reduction in the study drug(s):
≥Grade 4 neutropenia >5 days;
≥Grade 4 thrombopenia lasting ≥7 days;
≥Grade 3 anemia;
≥Grade 3 neutropenic fever with a single temperature of >38.3 degree C or a sustained temperature of ≥ 38 degree C for more than one hour;
any ≥Grade 3 non-hematologic toxicity with exception of nausea and vomiting, alopecia, drug-related fever;
≥Grade 3 serum creatinine;
bone marrow and renal function didn't recover to CTCAE Grade ≤ 1 of baseline at the Day 1 of the 2nd treatment course, the treatment can be postponed less than 2 weeks. DLT was recognized when the delayed duration was more than 2 weeks.

The plasma EB virus DNA load will be check by real-time quantitative polymerase chain reaction (PCR). These data will be collected every months when subjects enter this trial and finish their final treatment cycle one weeks, 3 months, and/or 6 months later. These data will be used to supplementary data for tumor status assessment.

Chang Gung Memorial Hospital

TTY Biopharm

D 1-14 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 22-35 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 31-35 Boceprevir 800mg tds D 52-56 Boceprevir 800mg tds

D 10-14 Boceprevir 800mg tds D 22-35 St. John's Wort 2 x 300mg (Ucalm(r)) QD D 31-35 Boceprevir 800mg tds D 43-56 St. John's Wort 2 x 300mg (Ucalm(r)) QD

All Participants

Sex: Female, Male

Region of Enrollment

Pharmacokinetic parameters (maximum and trough concentrations, and area under concentratof boceprevir and SJW will be evaluated when given in combination at steady-state to evaluate possible differences in concentrations during co-administration versus drug given alone.
The pharmacokinetic parameters calculated for boceprevir and SJW will be Ctrough,the maximum observed plasma concentration (Cmax), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve.
All pharmacokinetic parameters will be calculated using non-compartmental modelling techniques (WinNonlin®) and all statistical calculations performed within-participant changes in the assessed pharmacokinetic parameters (drug alone vs drug combination) will be evaluated by calculating geometric mean ratios.

Combined analysis of both group sequences

Pharmacokinetic of Boceprevir in the Presence of Ucalm (St John's Wort)

St John's Wort, (SJW) for 14 days (1-14)
[wash out for 7 days (15-21)]
SJW for 14 days (22-35) plus boceprevir from day 31 to day 35 (5 days in total)
[wash out for 7 days (36-42)]
boceprevir from day 52 to day 56

Group A (St John's Wort Then Boceprevir)

Boceprevir for 5 days (10-14)
[wash out for 7 days (15-21)]
SJW for 14 days (22-35) plus boceprevir from day 31 to day 35 (5 days in total)
[wash out for 7 days (36-42)
SJW from day 43 to day 56

Group B (Boceprevir Then St John's Wort)

First Intervention (14 Days or 5 Days)

Washout (7 Days)

Second Intervention (14 Days)

Third Intervention (14 Days or 5 Days)

Dr Akil Jackson

Group A

Group B

Hepatitis C

Boceprevir as Victrelis(r) 200mg capsules

Boceprevir

Each Ucalm(r) tablet contains 300mg of St Johns Wort extract

St John's Wort

St Stephen's AIDS Trust

Boceprevir and Ucalm (St John&Apos;s Wort)

Phase I Evaluation of the Pharmacokinetics and Safety of Boceprevir and Ucalm (St John&Apos;s Wort) When Co-administered to Male and Female Healthy Volunteers.

St Stephens Aids Trust

University of Liverpool

University of Turin, Italy

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab
Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets
Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.
Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Everolimus +Vinorelbine + Trastuzumab

Race (NIH/OMB)

Anatomic stage for NSCLC is the American Joint Committee on Cancer (AJCC) tumor, node, and metastases (TNM) system, which is based on:
Size of primary tumor (T) and whether it has grown into nearby areas. Spread to regional lymph nodes (N). Spread (metastasis; M) to other organs of the body. Once the T, N, and M categories have been determined, this information is combined into a prognostic group. Higher numbers mean the cancer is more advanced.

Stage at breast cancer diagnosis

Median time since first brain metastases (years)

Number of participants who received prior systemic chemotherapy.

Prior Systemic Chemotherapy (metastatic)

Prior metastatic chemotherapy lines, # (range)

Prior anti-Her2 (metastatic) Agents

Prior Central Nervous System Local Therapy

Recursive partitioning creates a decision tree that classifies members of a population by splitting it into sub-populations based on several dichotomous independent variables. The process is termed recursive because each sub-population may in turn be split an indefinite number of times.
This includes three classes: Class 1 (patients <65 years, ECOG Performance Status of 0-1, controlled primary tumor, and no extracranial metastases), Class 3 (ECOG Performance Status of 2 or greater), and Class 2 (all others);

Recursive Partitioning Analysis (RPA) Score

Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation.

Steroid use at baseline

Outside of the cranium (bones that surround the brain).

Extracranial disease at enrollment

response will be evaluated via gadolinium-enhanced brain MRI using modified RECIST criteria.
Complete Response (CR) - Disappearance of all target and nontarget lesions
Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion.
Stable Disease (SD) - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameter since the treatment started.
Progressive Disease (PD) - at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started AND an absolute increase in size of at least 5 mm in at least one target lesion OR the appearance of one or more new lesions of at least 6 mm in size.

Intracranial Objective Response Rate- Modified RECIST Criteria

Intracranial tumor lesions were evaluated via gadolinium-enhanced brain MRI using the MacDonald criteria. Measurable disease is defined as at least 1 measurable brain lesion accurately measured in at least 2 dimensions (longest diameter) as ≥5.0 mm. Tumor size is the product of the 2 longest bi-dimensional lines.
Complete Response (CR)- Disappearance of all tumor on consecutive CT or MRI scans at least 1 month apart, off steroids for treatment of neurological symptoms, and neurologically stable or improved.
Partial Response (PR)- ≥50% reduction in size of tumor on consecutive CT or MRI scans at least 1 month part, steroids stable or reduced, and neurologically stable or improved.
Progressive Disease (PD)- ≥25% increase in size of tumor or any new tumor on CT or MRI scans, or neurologically worse, and steroids stable or increased due to neurologic symptoms.
Stable Disease (SD)- all other situations Overall Response Rate (ORR) is the sum of partial responses (PRs) and CRs.

Intracranial Response Rate- MacDonald Criteria

Grade 3 or higher toxicities of interest are reported. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.
The NCI CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Toxicity

Time to intracranial progression after administration of everolimus in combination with trastuzumab and vinorelbine as defined via modified RECIST criteria.
Progressive Disease (PD) - at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started AND an absolute increase in size of at least 5 mm in at least one target lesion OR the appearance of one or more new lesions of at least 6 mm in size.

Time to Intracranial Progression.

Extracranial response was measured using RECIST 1.1 criteria and defined as the number of subjects achieving CR or PR.
Complete Response (CR) - Disappearance of all target and nontarget lesions Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion.
Stable Disease (SD) - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameter since the treatment started.
Progressive Disease (PD) - at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started AND an absolute increase in size of at least 5 mm in at least one target lesion OR the appearance of one or more new lesions of at least 6 mm in size.

Extracranial Response

To evaluate the extracranial time to progression as determined by RECIST 1.1 criteria after administration of everolimus in combination with trastuzumab and vinorelbine.
Progressive Disease (PD) - at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started AND an absolute increase in size of at least 5 mm in at least one target lesion OR the appearance of one or more new lesions of at least 6 mm in size.

Extracranial Time to Progression

Overall survival (OS) after administration of everolimus in combination with trastuzumab and vinorelbine

Overall Survival

The FACT-Br is a 23-question self-report questionnaire subscale administered with the Functional Assessment of Cancer Therapy- General (FACT-G) which contains concerns relevant to patients with brain tumors . Each question has a value 0-4. For some questions a higher indicates better outcome and others are the opposite. The former are summed as is, the latter are reversed in value before adding, such that each domain ranges from 0 to 4 times the number of questions in the domain, with 0 indicating worst and the highest possible value indicating best outcome. Total scores on the FACT-Br subscale range from 0 to 92 with lower scores indicating declining quality of life. The change from baseline is the difference in scores between the baseline and 9 week assessments.

Functional Assessment of Cancer Therapy- Brain (FACT-Br) Change From Baseline to Assess Impact of Everolimus in Combination With Trastuzumab and Vinorelbine on Quality of Life

The FACT-B is a 10-question self-report questionnaire subscale administered with the Functional Assessment of Cancer Therapy- General (FACT-G) which contains concerns relevant to patients with breast cancer. Each question has a value 0-4. For some questions a higher indicates better outcome and others are the opposite. The former are summed as is, the latter are reversed in value before adding, such that each domain ranges from 0 to 4 times the number of questions in the domain, with 0 indicating worst and the highest possible value indicating best outcome. Total scores on the FACT-B subscale range from 0 to 40 with lower scores indicating declining quality of life. The change from baseline is the difference in scores between the baseline and 9 week assessments.

Functional Assessment Cancer Therapy- Breast (FACT-B) From Baseline to 9 Weeks of Treatment to Assess Impact of Everolimus in Combination With Trastuzumab and Vinorelbine on Quality of Life

Overall Study

Robin V. Johnson

HER-2 Positive Breast Cancer

everolimus 5 mg PO daily as two 2.5-mg tablets

Everolimus

vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Vinorelbine

2 mg/kg IV administered over 30 minutes weekly

Trastuzumab

University Of Alabama at Birmingham

UNC Lineberger Comprehensive Cancer Center

Carolinas Healthcare System

Vanderbilt-Ingram Cancer Center

A Study Of Everolimus, Trastuzumab And Vinorelbine In HER2-Positive Breast Cancer Brain Metastases

A Phase II Study Evaluating The Efficacy And Tolerability Of Everolimus (RAD001) In Combination With Trastuzumab And Vinorelbine In The Treatment Of Progressive HER2-Positive Breast Cancer Brain Metastases

antviral/breast neoplasms

Oral Microbiome of Patients With Hepatitis C Virus Infection

Study of Cytolytic Viral Activation Therapy (CVAT) for Recurrent/Metastatic Nasopharyngeal Carcinoma

Boceprevir and Ucalm (St John&Apos;s Wort)

A Study Of Everolimus, Trastuzumab And Vinorelbine In HER2-Positive Breast Cancer Brain Metastases

Gene Therapy for the Treatment of Brain Tumors

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