cyrilzakka/clinical-trials huggingface dataset:
Study of Afatinib in Advanced Cutaneous Squamous Cell Carcinoma

The primary purpose of this study is to find out if Afatinib can help treat participants with advanced cSCC.


Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years at the time of informed consent
* ECOG performance status ≤2
* Adequate bone marrow, organ function and laboratory parameters:
* ANC ≥ 1.0 × 109/L;
* Hemoglobin ≥ 8 g/dL;
* Platelets ≥ 75 × 109/L;
* AST and ALT ≤5 × ULN
* Calculated creatinine clearance \> 15mL/min by Cockroft-Gault formula
* Histologic diagnosis of invasive cutaneous squamous cell carcinoma, that is deemed not appropriate for further surgical intervention and/or radiation therapy. Participants may have either locally advanced or metastatic disease.
* At least 1 measurable lesion - either per RECIST 1.1 criteria, or for patients with externally visible cuSCC lesion(s) not measurable on imaging, at least one lesion ≥1 cm in longer diameter, amenable to digital photography with bi-dimensional measurements
* Participants must have received prior immunotherapy with an anti-PD-1/PD-L1 antibody, if participant was deemed eligible (i.e., was not immunosuppressed or a transplant receipt, etc)
* Immunosuppressed participant including those with concurrent autoimmune diseases and solid organ transplant recipients are eligible
* Prior to first dose of study treatment, participant must be at least 2 weeks from any prior systemic therapy, major surgery or radiation
* Able to undergo a pre-treatment and on-treatment tumor biopsy
* Female participants of childbearing potential must have a negative serum or urine β-HCG test result. Female participants of childbearing potential and male participants must agree to use methods of contraception that are highly effective.
* Participants with brain metastases are permitted assuming that the brain metastases have been adequately treated with prior surgery or radiation.

Exclusion Criteria:

* In participants with known liver cirrhosis, those with severe (Child Pugh C) hepatic impairment will be excluded.
* Untreated, uncontrolled or symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable or require corticosteroids,
* Participants with mixed histologies (eg, sarcomatoid, adenosquamous) will generally not be eligible, unless the predominant histology is invasive cuSCC.
* Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to randomization. Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load prior to randomization.
* Pregnancy or breast feeding.
Lifestyle Intervention to Improve Insulin Sensitivity and Markers of Cardiovascular Risk in Prostate Cancer Survivors

The purpose of this study is to discover if intensive lifestyle changes (such as diet and increased physical activity) improve the body's sensitivity to insulin, and therefore help prevent diabetes and other cardiovascular disease, in men receiving GnRH hormone therapy for prostate cancer.

* In this study, participants will be divided into two groups. One group will undergo intensive lifestyle changes (Lifestyle Intervention Group) designed by the Diabetes Prevention Group, and the other (Control Group) will follow the guidelines for healthy living established by the Food Guide Pyramid and the National Cholesterol Education Program.
* All visits will take place at the General Clinical Research Center at the Massachusetts General Hospital.
* At the initial visit, the following will be performed: Bionutrition evaluation; Oral Glucose Tolerance Test (OGTT); additional blood work and; Dual Energy X-Ray Absorptiometry (DXA) Scan.
* After the initial visit, visits will be scheduled at 3, 6 and 12 months after and the above procedures will be repeated.
* Participants will be randomized into one of the two study groups. Lifestyle Intervention Group: The goal for participants assigned to this group are to achieve and maintain a weight loss of at least 7% of initial body weight through a healthy low calorie, low fat diet and to engage in physical activity of moderate intensity. Control Group: participants in this group will receive standard nutrition and exercise recommendations from the Food Guide Pyramid and the National Cholesterol Education Program Step 1 diet to reduce body weight and increase physical activity.

Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed prostate cancer
* Current Hormone therapy with GnRH agonist of 3 months or longer
* Overweight or obese (body mass index of 25kg/m2 or greater)
* No other conditions that prevent intensive lifestyle intervention

Exclusion Criteria:

* History of diabetes mellitus requiring drug therapy
* Hemoglobin Aic of 7% or greater
* Symptomatic metastatic disease
* Myocardial infarction within 6 months
* Treatment with anabolic agents or metabolic agents known to affect insulin or glucose levels
* Disease progression according to PSA Working Group Criteria
Study for MR Formulation of PF-06650833 in Healthy Adult Japanese Subjects

The purpose of this study is to evaluate the tolerability, safety and pharmacokinetics of PF-06650833 orally administered as modified release tablets in healthy Japanese subjects.


Eligibility Criteria:
Inclusion Criteria:

1. Healthy female subjects of non childbearing potential and/or male Japanese subjects between the ages of 20 and 55 years, inclusive.
2. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs).
3. Subject must have four Japanese grandparents who were born in Japan.
4. Evidence of a personally signed and dated informed consent document.
5. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
2. Any condition possibly affecting drug absorption (eg, gastrectomy).
3. A positive urine drug screen.
4. Smoking cigarettes with exceeding provided criteria.
5. History of regular alcohol consumption exceeding provided limitations.
6. Treatment with an investigational drug within a provided criteria.
7. Abnormal supine blood pressure.
8. Abnormal pulse rate.
9. Abnormal 12 lead ECG.
10. History of tuberculosis.
11. History of hepatitis or positive testing for HIV, hepatitis B surface antigen, hepatitis B surface antibodies, hepatitis B core antibodies, hepatitis C antibodies or syphilis.
12. Any medical history of disease (ie, Gilbert's disease).
13. Abnormal clinical laboratory test related to cardiac and skeletal muscle injury.
14. Male subjects with partners currently pregnant; unwilling or unable to use a highly effective method of contraception
15. Use of prescription or nonprescription drugs, vitaminic and dietary supplements within a specified duration.
16. Blood donation exceeding a provided limitation.
17. History of sensitivity to heparin or heparin induced thrombocytopenia.
18. History of cancer (other than treated basal cell and squamous cell carcinoma of the skin) in the previous 5 years.
19. Unwilling or unable to comply with the Lifestyle guidelines described in this protocol.
20. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
21. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality.
Pediatric MSC-AFP Sub-study for Crohn's Fistula

The purpose of this study is to determine the safety of using an autologous mesenchymal stromal cell (MSC) coated fistula plug in people with fistulizing Crohn's disease. Autologous means these cells to coat the plug come from the patient.

The investigators propose to study the safety of autologous mesenchymal stromal cell transfer using a biomatrix (the Gore Bio-A Fistula Plug) in a Phase I study using a single dose of 20 million cells. 5 patients (age 12 to 17 years) with Crohn's perianal fistulas will be enrolled.

Subjects will undergo standard adjuvant therapy including drainage of infection and placement of a draining seton. Six weeks post placement of the draining seton, the seton will be replaced with the MSC loaded Gore fistula plug as per current clinical practice. The subjects will be subsequently followed for fistula response and closure for 24 months. This is an autologous product derived from the patient and used only for the same patient.

Eligibility Criteria:
Inclusion Criteria

1. Males and females 12-17 years of age.
2. Residents of the United States.
3. Crohn's disease with single or multiple draining complex perianal fistulae (definition as below) for at least three months despite standard therapy (definition below).
4. Concurrent therapies with corticosteroids, 5-aminosalicylate (5-ASA) drugs, thiopurines, methotrexate (MTX), antibiotics, and anti-tumor necrosis factor (TNF) therapy are permitted.
5. All patients should have undergone a colonoscopy in last 12 months to rule out malignant or premalignant condition
6. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
7. Ability to comply with protocol
8. Competent and able to provide written informed consent (and assent where appropriate).
9. Must have failed standard medical therapy including anti-TNF agents

Exclusion Criteria

1. Inability to obtain informed consent (and assent where appropriate).
2. Clinically significant medical conditions within the six months before administration of MSCs: e.g. sepsis, pneumonia active serious infection or other conditions that would, in the opinion of the investigators, compromise the safety of the patient.
3. Specific exclusions;

   a. Evidence of hepatitis B, C, or HIV
4. History of cancer including melanoma (with the exception of localized skin cancers)
5. Investigational drug within thirty (30) days of baseline
6. A resident outside the United States
7. Pregnant or trying to become pregnant, or breast feeding.
8. History of clinically significant auto-immunity (other than Crohn's disease) or any previous example of fat-directed autoimmunity
9. Previous allergic reaction to a perianal fistula plug.
10. If adipose tissue is not technically feasible
11. Weight less than 35 kg
12. Allergic to local anesthetics
13. Non-enterocutaneous tracts (i.e. recto-vaginal, entero-vesicular)
Monogenic Diabetes Misdiagnosed as Type 1

The study has two aims:

1. To (1a) determine the frequency of monogenic diabetes misdiagnosed as type 1 diabetes (T1D) and (2) to define an algorithm for case selection.
2. To discover novel genes whose mutations cause monogenic diabetes misdiagnosed as T1D.

Aim 1. The investigators will recruit 5,000 cases diagnosed as T1D under the age of 25, from 17 participating clinics across Canada. All cases will be tested for four antibodies (against proinsulin, GAD65, islet antigen 2 (IA-2), and ZnT8). Cases negative for all four will be exome-sequenced.

1. Variant annotation will be focused on known monogenic diabetes genes. Variants rated as pathogenic, likely pathogenic or of unknown significance whose zygosity fits the genetic model, will be confirmed in a clinically certified laboratory and communicated to the treating health care team. End-point is the frequency of such variants compared to their frequency in control, non-T1D exomes.
2. The following variables will be examined for the ability to predict monogenic diabetes: Negativity for all autoantibodies tested, family history, polygenic T1D risk score, age of onset, sex, glycosylated hemoglobin (HbA1c), insulin dose, and presence of syndromic features. Predictors will be analyzed by multiple regression and results subjected to jackknife (leave-one-out) validation. Machine-learning techniques may be used.

Aim 2. Variants outside known genes in non-diagnostic exomes will be annotated and examined under autosomal dominant, recessive, X-linked and mitochondrial inheritance models. Corresponding frequency cutoffs will be 0.0005, 0.01, 0.001 and 0.0005 (if heteroplasmy \>70%). Formal mutation-burden analysis will be based on depth-adjusted data from the Genome Aggregation Database (gnomAD). Genes mutated in more than one unrelated proband will be examined by a statistical approach taking into account the presence of a large number of phenocopies (Akawi et al., Nat Genet. 2015;47:1363-1369). Genes that achieve statistical significance will be tested in additional cohorts with international collaborations.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of diabetes under the age of 25 as either type 1 or undetermined type.

Exclusion Criteria:

* Existing T1D autoantibody testing with a positive result
Study of Clevidipine Assessing Its Preoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-1)

The purpose of this study is to determine the efficacy of clevidipine injection versus placebo in treating preoperative hypertension.

Initiation of study drug infusion will commence with the occurrence of protocol-defined preoperative hypertension (SBP \> 160 mmHg) as measured via an indwelling arterial line.

The study drug (clevidipine or placebo) may be administered to treat hypertension until one hour has elapsed, or until induction of anesthesia, whichever occurs first.

The primary endpoint of bailout described (as defined per protocol) as bailout for lack of efficacy, bailout for safety reason or bailout due to treatment failure will be determined during the 30-minute period from study drug initiation.

Eligibility Criteria:
Pre-randomization Inclusion Criteria:

* Provide written informed consent before initiation of any study-related procedures.
* Be at least 18 years of age
* Be scheduled for cardiac surgery (including Coronary Artery Bypass Grafting \[CABG\], Off Pump Coronary Artery Bypass \[OPCAB\], Minimally Invasive Direct Coronary Artery Bypass \[MIDCAB\] surgery, and/or valve replacement/repair procedures)
* Have a recent history (within 6 months of randomization) of hypertension requiring treatment with antihypertensive medication(s) or be actively hypertensive upon admission

Pre-randomization Exclusion Criteria:

* Women of child-bearing potential (unless they have a negative pregnancy test)
* Recent cerebrovascular accident (within 3 months before randomization)
* Known intolerance to calcium channel blockers
* Allergy to soybean oil or egg lecithin (components of the lipid vehicle)
* Pre-existing left bundle branch block or permanent ventricular pacing
* Any other disease or condition, which, in the judgment of the investigator would place a patient at undue risk by being enrolled in the trial.
* Participation in another therapeutic drug or therapeutic device trial within 30 days of starting study

Post-randomization Inclusion Criteria:

* After the insertion of an arterial line, the patient is determined to meet the per protocol preoperative definition of hypertension, i.e. systolic blood pressure (SBP) \> 160 mmHg
* It is the investigator's intent to lower the patient's SBP by a minimum of 15% from its baseline value
The Effect of the Mobile Application Developed for Hemodialysis Patients on Symptoms and Disease Compliance

The aim of this study is to determine the effect of mobile-based education and counseling developed for hemodialysis patients on the symptoms experienced and the adaptation to the disease.

Patients with end-stage renal disease are faced with many symptoms both during the disease and during the hemodialysis treatment process. Likewise, this process brings with it problems of adaptation to the disease. Experiencing intense symptoms negatively affects compliance with the disease and hemodialysis treatment, and compliance problems complicate symptom management. Therefore, patients need information support that can increase symptom management and compliance. Considering today's technology, this information can be provided by mobile phone, especially due to ease of use and fast transportation. In order for patients to access accurate information and receive consultancy from experts, appropriate software and sustainable mobile applications must be included in the disease management process. Today, mobile applications are an integral part of daily life for millions of users worldwide and are increasingly used to receive and communicate fast and interactive information about various chronic diseases. With the mobile-based training and counseling to be applied in this study, it is aimed to enable patients receiving hemodialysis treatment to access professional information support more easily, to better manage the symptoms they experience due to the disease, and to increase their adaptation to the disease. For this reason, the effect of mobile-based training and counseling developed for patients receiving hemodialysis treatment on the symptoms experienced by the patients and their adaptation to the disease will be evaluated in this study.

Eligibility Criteria:
Inclusion Criteria:

* Chronic kidney failure patient
* Agreeing to be a voluntary participant,
* Receiving dialysis treatment for at least 3 months,
* 18 years and over,
* Able to understand and speak Turkish
* At least primary school graduate,
* Using a smart phone for at least one year,
* Having internet access at home or at work.
* Able to use internet

Exclusion Criteria:

* Speech, hearing and visual impairment,
* Having any psychiatric diagnosis or treatment that may interfere with perception (Alzheimer, schizophrenia, major depression)
* rheumatological diseases, fracture, joint health problem, amputation
A Study of the Safety and Tolerability of a Single Dose Administration of CVT-301 (Levodopa Inhalation Powder)

This study is a double-blind, randomized, placebo-controlled, 2-way crossover study to evaluate the safety of CVT-301 levodopa (l-dopa) when co- administered with the first daily dose of oral levodopa/carbidopa for early morning OFF symptoms in patients with Parkinson's disease (PD).

An "OFF state" is defined as the time when medication is no longer providing benefit with respect to mobility, slowness, and stiffness. OFF episodes may be heralded by non-motor symptoms (e.g., pain, anxiety) prior to the appearance of motor symptoms.

Eligibility Criteria:
Inclusion Criteria:

* have idiopathic PD (i.e., not induced by drugs or other diseases) as defined by fulfilling Steps 1 and 2 of the United Kingdom (UK) Brain Bank criteria, diagnosed after the age of 30 years
* diagnosis of Parkinson's disease and motor fluctuations and early morning OFF symptoms
* classified as Stage 1 to 3 on the modified Hoehn and Yahr scale for staging of PD severity (in an ON state)
* subjects who are on a l-dopa-containing therapy, not including Rytary (or equivalent), must be stable on oral l-dopa-containing therapy for at least 2 weeks prior to the Screening Visit with a l-dopa/decarboxylase inhibitor (DDI)-containing regimen
* subjects who are on a l-dopa-containing therapy, when including Rytary (or equivalent), should be on a stable dose for at least 6 weeks prior to the Screening Visit
* the frequency of l-dopa administrations must be at least 3 times during the waking day and a total daily l-dopa dose of ≤ 1600 mg.
* on a stable regimen of their standard PD medications
* on a stable regimen of any blood pressure reducing medications (if applicable) for at least 30 days prior to screening
* forced expiratory volume in one second (FEV1) ≥60% of predicted for race, age, sex, and height and FEV1/FVC (forced vital capacity) ratio ≥70%
* no clinically significant abnormalities that would affect ability to complete study as determined by medical history, physical examination, electrocardiogram, clinical laboratory test results
* negative drug and alcohol testing
* negative pregnancy test for all women.

Exclusion Criteria:

* participated in any prior study with CVT-301
* dyskinesia of a severity that would significantly interfere with the subject's ability to participate or perform study procedures (as determined by the UPDRS Part 4)
* any contraindication to performing routine spirometry or who are unable to perform a spirometry maneuver
* have a current history of symptomatic orthostatic hypotension or are treated with medications to treat orthostatic hypotension (for example droxidopa, fludrocortisone), if they have severe dysautonomia
* have chronic obstructive pulmonary disease (COPD), asthma, or another chronic respiratory disease within the last 5 years.
Hypersensitivity to Phosphodiesterase 5 Inhibition in Post-Traumatic Headache

To investigate whether sildenafil (phosphodiesterase 5 inhibitor) induces migraine-like headache in people with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI).


Eligibility Criteria:
Inclusion Criteria:

* Age 18 to 65 years of age upon entry into screening
* History of persistent headache attributed to mild traumatic injury to the head for ≥ 12 months and in accordance with the International Classification of Headache Disorders, 3rd Edition (ICHD-3)
* ≥ 4 monthly headache days on average across the 3 months prior to screening
* Provision of informed consent prior to initiation of any study-specific activities/procedures

Exclusion Criteria:

* \> 1 mild traumatic injury to the head
* History of any primary or secondary headache disorder prior to mild traumatic injury to the head (except for infrequent episodic tension-type headache)
* History of moderate or severe injury to the head
* History of whiplash injury
* History of craniotomy
* History or evidence of any other clinically significant disorder, condition or disease (except for those outlined above) than, in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion
* The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior
* Female subjects of childbearing potential with a positive pregnancy test during any study visit
* Cardiovascular disease of any kind, including cerebrovascular diseases
* Hypertension (systolic blood pressure of ≥150 mmHg and/or diastolic blood pressure of ≥100 mmHg) prior to the start of infusion on the experimental day
* Hypotension (systolic blood pressure of ≤90 mmHg and/or diastolic blood pressure of ≤50 mmHg)
* Initiation, discontinuation, or change of dosing of prophylactic medications within 2 months prior to study inclusion
* Intake of acute medications (e.g. analgesics, triptans) within 48 hours of infusion start
* Baseline headache intensity of \>3 on an 11-point numeric rating scale (0 being no headache, 10 being the worst imaginable headache)
* Baseline headache with migraine-like features or self-reported baseline headache that mimics the subjects' usual headache with migraine-like features