cyrilzakka/clinical-trials huggingface dataset:
Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer

The purpose of this trial is to inform the future clinical development of the two investigational agents in ER+ breast cancer, LEE011 (CDK4/6 inhibitor) and BYL719 (PI3K-alpha inhibitor).

This is a multi-center, open-label Phase Ib study. The Phase Ib dose escalation will estimate the MTD and/or RP2D for three regimens: two double combinations, LEE011 with letrozole and BYL719 with letrozole, followed by triple combinations of LEE011 + BYL719 with letrozole (Arms 3 and 4).

The Phase Ib dose escalation part will be followed by Phase Ib dose expansions to further characterize the safety, tolerability, PK and preliminary clinical anti-tumor activity of the combinations. Optional crossover for patients who have progressed while on dose escalation or dose expansion with doublet treatment on Arms 1 or 2 to be treated with the triplet combination (Arm 3) after the determination of the RP2D for Arm 3; is no longer permitted after protocol amendment 6.

Approximately 270 adult women with ER+/HER2- locally advanced or metastatic breast cancer will be enrolled.


Eligibility Criteria:
Inclusion Criteria:

* Postmenopausal, Estrogen-receptor positive and/or Progesterone-receptor positive breast cancer
* Phase Ib dose escalation only: Any number of prior lines of endocrine therapy is allowed with the exception of cytotoxic therapy which is limited to one prior line administered in the advanced (metastatic or locally advanced) setting.
* Phase Ib dose expansions Arms 1, 2 and 3
* No prior systemic treatment in the advanced (metastatic or locally advanced) setting with the exception of treatment with letrozole for a maximum of one month prior to starting study treatment.
* Patients who received (neo)adjuvant therapy for breast cancer are eligible. Prior therapy with letrozole or anastrozole in the (neo)adjuvant setting is permitted if the disease-free interval is greater than 12 months from the completion of treatment.

Exclusion Criteria:

* HER2-overexpression in the patient's tumor tissue
* Patients with active CNS or other brain metastases
* Major surgery within 2 weeks
* Acute or chronic pancreatitis
* Bilateral diffuse lymphangitic carcinomatosis
* Another malignancy within 3 years
* Receiving hormone replacement therapy that cannot be discontinued
* Impaired cardiac function
* Patients with clinically manifest diabetes mellitus (treated and/or clinical signs or with fasting glucose ≥ 126 mg/dL / 7.0 mmol/L or hemoglobin A1c \>6.5%), history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus.
* Other protocol-defined inclusion/exclusion criteria may apply
Safety and Efficacy of FE 999326 Administered Intravesically to Japanese Subjects with High-grade, BCG Unresponsive, Non-muscle Invasive Bladder Cancer (NMIBC)

To evaluate the safety and efficacy of FE 999326 in Japanese subjects with high-grade, BCG unresponsive NMIBC.


Eligibility Criteria:
Inclusion Criteria:

* Have at entry, confirmed by a pathology report:

  1. Carcinoma in situ (CIS) only
  2. Ta/T1 high-grade disease with concomitant CIS or
  3. Ta/T1 high-grade disease without concomitant CIS
* Subjects who did not respond to BCG treatment and have a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response to BCG, relapse with CIS within 12 months of their last intravesical treatment with BCG or relapse with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.
* Life expectancy \>2 years, in the opinion of the investigator
* Eastern Cooperative Oncology Group (ECOG) status 2 or less
* Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra
* Subjects with prostate cancer on active surveillance at low risk for progression, defined as prostate-specific antigen (PSA) \<10 ng/dL

Exclusion Criteria:

* Current or previous evidence of muscle invasive (muscularis propria) or metastatic disease presented at the screening visit.
* Current systemic therapy for bladder cancer
* Current or prior investigational treatment for BCG unresponsive NMIBC or any other investigational drug within 1 month prior to screening
* Current or prior pelvic external beam radiotherapy within 5 years of entry
* Use of other adenovirus vector medications, including COVID-19 vaccines, within 2 weeks before and after instillation
* History of malignancy of other organ system within past 5 years, except treated basal cell carcinoma or squamous cell carcinoma of the skin and ≤pT2 upper tract urothelial carcinoma at least 24 months after nephroureterectomy.
* Subjects who cannot hold instillation for 1 hour
* Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation
* Intravesical therapy within 8 weeks prior to beginning trial treatment, with the exception of:

  * Cytotoxic agents when administered as a single instillation immediately following a TURBT procedure
  * Previous intravesical BCG therapy
* Systemic immunosuppressive therapy within 3 months prior to screening
Ketamine or Neostigmine for Serratus Anterior Plane Block in Modified Radical Mastectomy

The aim of this study is to Investigate the analgesic efficacy of adding ketamine compared to neostigmine to local anesthetic in Ultrasound guided Serratus anterior plane block for patients undergoing Modified Radical Mastectomy.

Breast cancer is the most common malignancy among females with incidence of 18,660 patients each year in Egypt. Modified Radical Mastectomy is considered the main surgical management for breast cancer accounting for 31% of all breast surgery cases.

Ultrasound guided Serratus anterior plane block provides analgesia for breast and lateral thoracic wall surgeries by blocking nerves that are located in a compartment between the serratus anterior and the latissimus dorsi muscles ( the intercostobrachial nerve, lateral cutaneous branches of the intercostal nerves (T3-T9), long thoracic nerve and thoracodorsal nerve).

A previous study demonstrated the analgesic efficacy of ketamine in patients undergoing modified pectoral nerve block in breast cancer surgery as evidenced by prolonged time to first rescue analgesia and reduced total opioid consumption.

Neostigmine has been used as an additive to local anesthetics to prolong the analgesic effect. Although there is good evidence for a spinal action of neostigmine, its analgesic efficacy as an adjuvant to local anesthetic is still unclear.

The aim of this study is to Investigate the analgesic efficacy of adding ketamine compared to neostigmine to local anesthetic in Ultrasound guided Serratus anterior plane block for patients undergoing Modified Radical Mastectomy.

Eligibility Criteria:
Inclusion Criteria:

* ● Female patients

  * Type of surgery; Modified Radical Mastectomy (MRM).
  * Physical status ASA II, III.
  * Age ≥ 21 and ≤ 65 Years.
  * Body mass index (BMI): \> 20 kg/m2 and \< 35 kg/m2.

Exclusion Criteria:

* ● Patients with Known sensitivity or contraindication to drug used in the study (local anesthetics, opioids).

  * History of psychological disorders and/or chronic pain.
  * Contraindication to regional anesthesia e.g. local sepsis, pre- existing peripheral neuropathies and coagulopathy.
  * Infection of the skin at the site of needle puncture area
  * Patient refusal.
  * Severe respiratory or cardiac disorders.
  * Advanced liver or kidney disease.
  * Pregnancy.
  * Patient with surgery duration more than two hours
Effect of Black Tea on Vascular Function

Epidemiological studies indicate that regular consumption of three cups of black tea per day reduces the risk of stroke or myocardial infarction. In a number of previous nutrition intervention studies tea has been shown to improve vascular function as assessed by Flow Mediated Dilation (FMD).

The current study tests a specific Black tea extract against a placebo in population that has previously show to be sensitive to the effect of black tea on Flow Mediated dilation. A tea extract that has previously been shown to improve FMD is included as the positive control.

Eligibility Criteria:
Inclusion Criteria:

* Apparently healthy male volunteers with no history of cardiovascular disease
* Having body mass index (BMI) of between 18.0 and 30.0 kg/m2 (inclusive)
* Non-smokers (\> 2 years)
* Non-tea drinkers (less or equal 1 cup/week)
* Limited alcohol intake (less or equal 21 units/week)
* Systolic blood pressure less or equal 160 mmHg and/or diastolic blood pressure less or equal 100 mmHg at screening
* Brachial artery can be imaged using ultrasound and at screening FMD value is within the expected range as judged by the PI
* Judged to be in good health on the basis of medical history, physical examination and routine laboratory tests (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose, highly sensitive C-reactive protein).
Efficacy and Safety of Zoledronic Acid in Patients With Bone Metastases of Any Solid Tumors or Multiple Myeloma

Zoledronic acid is a medication that slows the breakdown of bone. This study will assess the efficacy and safety of zoledronic acid in Chinese patients with multiple myeloma or other solid tumors with bone metastases.


Eligibility Criteria:
Inclusion Criteria

* Cancer patients (multiple myeloma or other solid tumors) and confirmed evidence of bone lesions
* Significant bone pain

Exclusion Criteria

* Poor renal function
* Use of other investigational drugs within 30 days of visit 2
* Dental or other surgery to the jaw within 6 weeks of screening, or planned during the 4 week study

Other protocol-defined exclusion criteria may apply.
Carpal Tunnel Release With Risk Factors for Amyloidosis

Bilateral carpal tunnel syndrome has been demonstrated in previous literature to be a warning sign for potential amyloidosis. One study has been performed in which patients with bilateral carpal tunnel syndrome underwent tissue biopsy (either tendon sheath or transverse carpal ligament) at the time of carpal tunnel release to determine the strength of association as well as most common subtypes. However, no study has been done demonstrating whether or not patients with amyloid-positive carpal tunnel biopsy would benefit from an early referral to cardiology for a work-up of potential cardiac amyloidosis. In our study, patients with bilateral carpal tunnel symptoms who are indicated for carpal tunnel release would be identified in clinic and undergo biopsy for congo red staining at the time of surgery. All patients with positive biopsy results would be referred to cardiology. Outcomes would include the rate of amyloid positivity, common subtypes, and echocardiographic findings after cardiac referral.


Eligibility Criteria:
Inclusion Criteria:

Positive screening is defined as two characteristics from Tier 1 or one characteristic from Tier 1 and one from Tier 2 Tier 1

* Male \> 50 years old
* Female \> 60 years old
* Bilateral carpal tunnel symptoms or prior release surgery Tier 2
* Spinal stenosis
* History of biceps tendon rupture
* Atrial fibrillation or flutter (active or previous history)
* Pacemaker
* Congestive heart failure
* Family history of transthyretin amyloidosis (ATTR)

Exclusion Criteria:

* Unable or unwilling to follow up with cardiology.
* Previous diagnosis of cardiac amyloidosis.
Shuxuening Injection in the Treatment With Intravenous Thrombolysis in Patients With Ischemic Stroke (SHINY)

Shuxuening injection is a multi-target neuroprotective agent, it is expected to play a neuroprotective role on the basis of intravenous thrombolysis therapy. The primary purpose of this multicenter, randomized, double-blind, placebo-parallel controlled trial is to evaluate the efficacy and safety of Shuxuening injection in the treatment with intravenous thrombolysis in patients with ischemic stroke.

Intravenous thrombolysis with rt-PA within the time window is the most effective drug for acute ischemic stroke, but there are still more than 50% patients with functional disability. Neuroprotective agents can reduce brain cell death after cerebral ischemia by blocking all links of ischemic cascade. Shuxuening injection is a multi-target neuroprotective agent, it is expected to play a neuroprotective role on the basis of intravenous thrombolysis therapy.

This study is a multicenter, randomized, double-blind, placebo-parallel controlled trial. A total of 1380 patients from 50 centers in China who could be treated within 6 hours of onset and have received or plan to undergo intravenous thrombolytic therapy will be enrolled and randomly assigned, in a 1:1 ratio, to receive Shuxuening injection (20 ml Shuxuening injection + 250 ml 0.9% sodium chloride injection), or to receive Shuxuening injection placebo (20 ml plus 250 ml 0.9% sodium chloride injection); both groups are treated for 10-14 days. The primary efficacy outcome is mRS Score 0 to 1 at 90 days, and the primary safety outcome is adverse events within 90 days.

Eligibility Criteria:
Inclusion Criteria:

* Age 18 or older;
* Diagnosed with acute ischemic stroke;
* Within 6 hours of onset;
* Having received or plan to undergo intravenous thrombolytic therapy;
* NIHISS score of 4 to 25 points at enrollment;
* Signed informed consent.

Exclusion Criteria:

* mRS score greater than 1 point before the onset;
* Receiving neuroprotective agents, such as edaravone, edaravone dextrocamphorol, butylphthalein, etc. after the onset;
* Bleeding or other pathological brain disorders, such as vascular malformations, tumors, abscesses, or other common non-ischemic brain diseases (such as multiple sclerosis), detected by CT/MRI;
* History of clotting disorders, systemic bleeding, thrombocytopenia, or neutropenia;
* Severe hepatic or renal insufficiency (severe hepatic insufficiency refers to the ALT or AST levels above 3 times the upper limit of normal; severe renal insufficiency refers to the creatinine levels above 2 times the upper limit of normal);
* Allergic to Shuxuening injection or preparations containing ginkgo biloba (ginkgo biloba extract);
* Women who are pregnant or breastfeeding, and women of childbearing age who have a negative pregnancy test but refuse to take effective contraceptive measures;
* Participation in another clinical trial with an experimental product during the last 30 days;
* Other participants deemed unsuitable for participation in this study by the investigator.
Paliperidone Extended Release(ER) Effectiveness Study to Evaluate the Objective Symptom Change and Symptomatic Remission

The purpose of this study is to investigate the safety and efficacy of flexibly dosed paliperidone extended-release (ER) in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self).

This is an open-label, prospective (study following participants forward in time), single arm, and non-comparative study of paliperidone Extended Release(ER) in participants with schizophrenia (after switching from the existing drug to paliperidone ER). The total study duration will be approximately of 48 weeks per participant. The study consists of 2 parts: Screening (that is, 14 days before study commences on Day 1); Treatment (single-oral dose of paliperidone for 48 weeks, dose ranging from 3 to 12 milligram). Efficacy of the participants will primarily be evaluated by Positive and Negative Syndrome Scale. Participants' safety will be monitored throughout the study.

Eligibility Criteria:
Inclusion Criteria:

* Childbearing potential women who consent to the use of the consistently permissible contraception (oral contraceptive, contraceptive injection, intrauterine device, double barrier method and contraceptive patch)
* Participants who are compliant with self-medication or can receive consistent help or support
* Participants who need to change the antipsychotic drug to another one for the following reasons among the participants treated with an antipsychotic drug for more than two weeks before the screening (1) Group of lack of efficacy: the antipsychotic drug is clinically required to be changed because there is no or little therapeutic response despite the appropriately dosed antipsychotic therapy (2) Group of lack of tolerance: the antipsychotic drug is required to be changed due to lack of tolerance to the existing antipsychotic drug or the safety issue (3) Group of lack of compliance: the antipsychotic drug is required to be changed due to lack of medication compliance or the participant wants to change the antipsychotic drug)
* Have schizophrenia diagnosis by Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)

Exclusion Criteria:

* Participants with the past history of neuroleptic malignant syndrome (NMS)
* Participants who are suspicious of having clinically significant risk including suicide or aggressive behavior and are expected to unable to complete the study(based on the investigator's judgment)
* Participants with severe preexisting gastrointestinal narrowing (pathologic or iatrogenic) or participants who cannot swallow the drug whole (the study drug must not be chewed, divided, melted or grinded because it can impact the study drug release profile)
* Participants with significant abnormal findings in blood chemistry, hematological and urine analyses which are clinically significant at the investigator's discretion
* Female Participants who are pregnant or are breast feeding
The Effectiveness of Two Anti-HIV Treatments in HIV-Infected Patients

To determine the effects of zidovudine (AZT) alone and in combination with didanosine (ddI) on viral load in the lymphoid tissue and blood of antiretroviral-naive, HIV-infected patients with CD4 counts greater than or equal to 550 cells/mm3.

Recent studies have shown that during the asymptomatic phase (clinical latency) of HIV infection, there is an extraordinarily large number of infected CD4+ lymphocytes and macrophages throughout the lymphoid system, both in latent and productive states. These findings support the belief that early intervention therapy with reverse transcriptase inhibitors could prolong the clinical latency period.

Recent studies have shown that during the asymptomatic phase (clinical latency) of HIV infection, there is an extraordinarily large number of infected CD4+ lymphocytes and macrophages throughout the lymphoid system, both in latent and productive states. These findings support the belief that early intervention therapy with reverse transcriptase inhibitors could prolong the clinical latency period.

Patients are randomized to receive AZT alone, AZT plus ddI, or no therapy (placebo) daily for 48 weeks. Patients are followed at weeks 2, 4, and 8, and then every 8 weeks thereafter until week 48.

Eligibility Criteria:
Inclusion Criteria

Concurrent Medication:

Allowed:

* Antibiotics for bacterial infections as clinically indicated.
* Recombinant erythropoietin (EPO) and G-CSF as clinically indicated for grade 3 or worse anemia and neutropenia, respectively.
* Antipyretics.
* Analgesics.
* Allergy medications.
* Oral contraceptives.
* Nonprescription medications such as vitamins or herbal therapies.

Concurrent Treatment:

Allowed:

* Radiation therapy to local lesion only.
* Acupuncture.

Patients must have:

* HIV seropositivity.
* CD4 count \>= 550 cells/mm3.
* No ARC or AIDS conditions by CDC criteria.
* Consent of parent or guardian if less than 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Presence of factors predisposing to pancreatitis such as active alcoholism.
* Other medical conditions that would interfere with study compliance.

Concurrent Medication:

Excluded:

* Other antiretrovirals or systemic immunomodulators.
* Systemic corticosteroids.
* Systemic cytotoxic chemotherapy.
* Intravenous pentamidine.

Concurrent Treatment:

Excluded:

* Radiation therapy except to local lesion.

Patients with the following prior conditions are excluded:

* History of chronic diarrhea, defined as more than four loose or watery stools on average daily for the past month.
* History of grade 2 or worse peripheral neuropathy.
* History of pancreatitis.
* Bacterial infection requiring antibiotics within 14 days prior to study entry.

Prior Medication:

Excluded:

* Prior HIV therapy with antiretrovirals or systemic immunomodulators.

Prior Treatment:

Excluded within 2 weeks prior to study entry:

* Transfusion.

Active substance abuse or alcoholism.
Oxytocin Pathways and the Health Effects of Human-Animal Interaction

This study investigates the roles of oxytocin pathways in human-animal interaction.

This study investigates the roles of oxytocin pathways in human-animal interaction. Children will participate in three conditions involving friendly interactions with dogs, or play with toys at a university laboratory. Child and dog saliva and urine will be assayed for oxytocin concentrations. We will assess variation in oxytocin concentrations in relation to different experimental conditions, and in relation to specific behaviors and psychological constructs.

Eligibility Criteria:
Inclusion Criteria:

* Participants in this study will include typically-developing children between 8-10 years who have lived with a companion dog in the household for at least 6 months.

Exclusion Criteria:

* known medical diseases or injuries involving the central nervous or endocrine systems, major physical abnormalities, seizures, and significant sensory, cognitive, or motor impairments, current use of psychoactive medications
Comparison of Fixation Suture Type in Glaucoma Surgery

The aim of the study is to compare the effectiveness and safety of two types of intraoperative eye fixation: for the superior rectus muscle and traction suture in the peripheral cornea.

This is a prospective randomized trial with a 6 month follow-up period, which covers patients with open angle glaucoma qualified for combined glaucoma procedure (phacotrabeculectomy). In I group, the intraoperatively fixation in the peripheral part of the cornea is used, in II group the bridle suture for the superior rectus muscle is performed.

The way of the intraoperatively fixation may have some impact for postoperative results of the level of intraocular pressure (IOP), visual acuity (BCVA) and the incidence of upper eyelid ptosis was determined as a post-operative MRD (margin reflex distance) ≥2mm.

Eligibility Criteria:
Inclusion Criteria:

* co-existing glaucoma and cataract (NC1, NC2) classified by means of the LOCS III scale (Lens Opacities Classification System III)
* primary open-angle glaucoma and secondary pseudoexfoliative glaucoma, in which a satisfactory IOP level was not achieved despite maximum tolerable hypotensive treatment, both topical and systemic
* documented progression of loss of field of vision
* significant daily IOP fluctuations
* no cooperation from patient with regard to application of anti-glaucoma treatment, allergy to topical medications

Exclusion Criteria:

* no consent to participation in the study
* prior surgical and laser procedures in the area of the eye
* narrow- or closed-angle glaucoma
* post-inflammatory or post-traumatic secondary glaucoma
* chronic illness of the cornea or optic nerve
* advanced macular degeneration
* active inflammatory process
* pregnancy
* systemic steroid therapy