Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Disease Progression

Breast Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Letrozole

Estrogens

Palbociclib

Prolactin Release-Inhibiting Factors

Anastrozole

Aromatase Inhibitors

Hormone Antagonists

Estrogen Antagonists

Estrogen Receptor Antagonists

Enzyme Inhibitors

Protein Kinase Inhibitors

Antineoplastic Agents, Hormonal

The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily)

The patients will recieve anastrozole (1 mg, PO, once daily) or letrozole (2.5 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)

Dosage formulation: AZD9833 tablets will be administered orally

AZD9833

Dosage formulation: AZD9833 placebo tablets will be administrated orally.

AZD9833 Placebo

Dosage formulation: anastrozole tablets will be administered orally.

Dosage formulation: anastrozole placebo tablets will be administrated orally.

Anastrozole placebo

Dosage formulation: letrozole tablets will be administered orally.

Dosage formulation: letrozole placebo tablets will be administered orally.

Letrozole placebo

Dosage formulation: palbociclib tablets/capsules will be administered orally

Dosage formulation: abemaciclib tablets will be administered orally

Abemaciclib

Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.

Luteinizing hormone-releasing hormone (LHRH) agonist

Dosage formulation: ribociclib tablets will be administered orally

Ribociclib

AstraZeneca Clinical Study Information Center

The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor (palbociclib, abemaciclib or ribociclib) versus aromatase inhibitors (anastrozole or letrozole) in combination with CDK4/6 inhibitor in patients with hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer with detectable ESR1 mutation.

Breast cancer is the most common type of cancer among women. In people with breast cancer, the body is not able to control the growth of some cells. These extra cells can form tumors in the breast. When tumor cells move to different parts of the body this is called advanced cancer. Researchers are looking for better ways to treat advanced breast cancer.

This trial will look at six drugs: palbociclib, abemaciclib, ribociclib, letrozole, anastrozole, and AZD9833. AZD9833 is the trial drug, and is the only drug not yet approved for use. Palbociclib, abemaciclib and ribociclib work in the same way and are a type of cancer drug called a CDK4/6 inhibitor. Letrozole and anastrozole work in the same way and are both a type of cancer drug called an aromatase inhibitor (AI). CDK4/6 inhibitors and AIs work together to block the tumor's ability to grow. These drugs have been approved for combined use in people with advanced breast cancer that is HR-positive and HER2-negative. But if people get mutations in the ESR1 gene, it can make the AI and CDK4/6 inhibitor treatment work less well.

The trial drug, AZD9833, is designed to work with a CDK4/6 inhibitor in the same way that an AI does. Researchers think that AZD9833 might work better with a CDK4/6 inhibitor than an AI does in people who get mutations in their ESR1 gene.

Participants in this trial will have already been receiving one of the following combinations of a CDK4/6 inhibitor and an AI:

* palbociclib + anastrozole
* palbociclib + letrozole
* abemaciclib + anastrozole
* abemaciclib + letrozole
* ribociclib + anastrozole
* ribociclib + letrozole

During the trial, participants will remain on the same CDK4/6 inhibitor that they were taking before the trial.

In this trial, the researchers want to find out how well switching a participant with an ESR1 gene mutation from an AI (letrozole or anastrozole) to AZD9833 works in the treatment of advanced breast cancer that is HR-positive and HER2-negative.

The researchers will look at which trial treatment helps the participants live longer with the cancer before it gets worse.

The researchers also want to know more about how safe AZD9833 is.

The trial participants will be split into 2 groups:

* Participants in Group A will receive AZD9833, a CDK4/6 inhibitor, and a placebo
* Participants in Group B will receive an AI, a CDK4/6 inhibitor, and a placebo

A placebo looks like a treatment but does not have any medicine in it.

A computer program will be used to randomly choose the treatments each participant gets. This helps make sure the groups are chosen fairly. Researchers do this so that comparing the results of each treatment will be as accurate as possible.

The participants will take their trial treatments over 28-day cycles, with a placebo and either AZD9833 or an AI taken once daily by mouth for all 28 days. If the participant is taking abemaciclib, they will take it twice daily by mouth for all 28 days. If the participant is taking palbociclib or ribociclib, they will take it once daily by mouth for 21 days and then stop taking it for the final 7 days of the cycle. The participant will then repeat the 28-day cycle receiving the trial treatment in the same way for as long as they are in the trial.

Participants will visit their trial site regularly throughout the trial. At these visits, the trial doctors will check the health of the participants. They will also take blood samples and do scans of the participants' tumors.

Participants will take their trial treatment until their cancer gets worse or they decide to leave the trial.

\*Palbociclib and Abemacliclib cohorts are currently ongoing. Ribociclib cohort will be open pending on availability of the data.

Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)

A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole)+ CDK4/6 Inhibitor in HR+/HER2-MBC Patients With Detectable ESR1Mutation Without Disease Progression During 1L Treatment With Aromatase Inhibitor+ CDK4/6 Inhibitor- A ctDNA Guided Early Switch Study

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death.

PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.

The OS is defined as the time from randomization to death due to any cause.

Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause.

ORR is defined as the proportion of patients who have a complete response (CR) or partial response (PR), as determined by the investigator at local site per RECIST 1.1.

CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for At least 23 weeks after randomisation for each patient to allow for an early assessment within the assessment window (1 week window for RECIST assessment)

Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden.

To assess the steady state PK of AZD9833 in combination with palbociclib or abemaciclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration.

AstraZeneca

Skin Diseases

The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)

The patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)

Dosage formulation: Anastrozole tablets will be administered orally.

AZD9833 placebo

The study is intended to show superiority of AZD9833 in combination with palbociclib (a CDK4/6 inhibitor) versus anastrozole (an aromatase inhibitor) and palbociclib as the initial treatment of patients with hormone receptor-positive (ER-positive), human epidermal growth factor 2-negative (HER2-negative) advanced/metastatic breast cancer.

INFORMATION FOR TRIAL PARTICIPANTS

In this trial, the researchers will look at how well camizestrant with palbociclib works, compared with anastrozole with palbociclib, in participants with breast cancer that has either spread into other parts of the body at the time of diagnosis, or has come back after at least 2 years of standard endocrine treatment.

Participants in this trial will have breast cancer that has ER proteins but does not have overexpression of HER2 protein.

A Randomised, Multicentre, Double-Blind, Phase III study will evaluate the safety and efficacy of AZD9833 (next generation oral SERD) in combination with palbociclib versus anastrozole in combination with palbociclib for the treatment of patients with ER-positive breast cancer. The goal of the study is to demonstrate superiority of AZD9833 over anastrozole in the context of combination with palbociclib in first line setting.

INFORMATION FOR TRIAL PARTICIPANTS

Researchers are looking for a better way to treat breast cancer.

In people with cancer, some cells have grown out of control to form tumours.

The trial drugs palbociclib, camizestrant, and anastrozole are designed to work by blocking the cancer's ability to grow. Camizestrant is also called AZD9833. Palbociclib and anastrozole are already available as treatments for people with certain type of breast cancer.

In this trial, the researchers want to find out how well taking camizestrant with palbociclib, or anastrozole with palbociclib, works in participants with breast cancer that has ER proteins but does not have overexpression of HER2 protein.

The researchers will look at which trial treatments help the participants live longer with cancer before it gets worse.

The trial will split participants into 2 groups:

* Participants in Group 1 will take camizestrant, palbociclib, and a placebo matched with anastrazole.
* Participants in Group 2 will take anastrozole, palbociclib, , and a placebo matched with camizestrant.

A placebo looks like a treatment but does not have any medicine in it.

A computer program will be used to randomly choose the treatments each participant gets. This helps make sure the groups are chosen fairly. Researchers do this so that comparing the results of each treatment will be as accurate as possible.

The participants will take their trial treatments in periods called "cycles". Each cycle will last 28 days. During each cycle, the participants will take:

* camizestrant or anastrozole once daily by mouth
* palbociclib once daily by mouth for 21 days. Then, they will not take any palbociclib for 7 days

Some participants will also get either goserelin or leuprorelin once every month. Participants could get goserelin or leuprorelin if:

* They are medically determined yet to reach menopause status
* They are male

They will get this treatment as an injection under the skin or into a muscle. Goserelin and leuprorelin work by decreasing the amount of sex hormones made by the body which will lead to reduction of ER production. This can help stop breast cancer from growing.

Participants will take trial treatment until the cancer gets worse or they leave the trial.

Participants will visit their trial site several times throughout the trial. At these visits, the trial doctors will check the health of the participants. They will also take blood samples and do scans of the participants' tumors.

A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease

SERENA-4: A Randomised, Multicentre, Double-Blind, Phase III Study of AZD9833 (an Oral SERD) Plus Palbociclib Versus Anastrozole Plus Palbociclib for the Treatment of Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease

PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death.

Time to second progression or death (PFS2) will be defined as the time from randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.

ORR is defined as the proportion of patients who have a CR or partial response, as determined by the investigator at local site per RECIST 1.1.

The DoR will be defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.

TFST is defined as time from randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.

CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for at least 23 weeks after randomization (to allow for an early assessment within the assessment window).

TSST is defined as time from randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause.

To assess the steady state PK of AZD9833 in combination with palbociclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration.

Change from baseline in EORTC QLQ-C30 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.

Change from baseline in EORTC QLQ-BR45 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.

Antirheumatic Agents

Anti-Infective Agents

Trastuzumab

Cyclophosphamide

Docetaxel

Epirubicin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

8 mg/kg i.v. loading dose over 90 mins in Cycle 1 and 6 mg/kg i.v. dose every 3 weeks over 60 mins then 30 mins for subsequent cycles (cycles 2-8), followed by surgery, then adjuvant period of 8mg/kg i.v. loading dose over 90 mins in cycle 9, and subsequent 6mg/kg (if therapy is missed by \>1 week, a re-loading dose of 8mg/kg should be given) over 30 mins for subsequent 9 cycles (cycles 10-18), disease progression, unacceptable toxicity, non-compliance, or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever occurs first.

Neoadjuvant chemotherapy:

Cycles 1-4: Docetaxel 75 mg/m² on day 1 of each 3-weeks cycle via 1h i.v. Infusion Cycles 5-8: EC on day 1 of each 3-weeks cycle: Epirubicin 75 mg/m² via 3-30 mins i.v. Infusion, Cyclophosphamide 500 mg/m² via 3-30 mins i.v. Infusion

8 mg/kg i.v. loading dose over 90 mins in Cycle 1 and 6 mg/kg i.v. dose every 3 weeks over 60 mins then 30 mins for subsequent cycles (cycles 2 -8) for cycles 2-8, followed by surgery, and subsequent adjuvant period of 8mg/kg i.v. loading dose over 90 mins in cycle 9, then 6mg/kg (if therapy is missed by \>1 week, a re-loading dose of 8mg/kg should be given) over 30 mins for subsequent 9 cycles (cycles 10-18), disease progression, unacceptable toxicity, non-compliance, or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever occurs first.

Neoadjuvant chemotherapy:

Cycles 1-4: Docetaxel 75 mg/m² on day 1 of each 3-weeks cycle via 1h i.v. Infusion Cycles 5-8: EC on day 1 of each 3-weeks cycle: Epirubicin 75 mg/m² via 3-30 mins i.v. Infusion, Cyclophosphamide 500 mg/m² via 3-30 mins i.v. Infusion

Loading dose of 8mg/kg in Cycle 1 and 6mg/kg in subsequent cycles.

HD201

Herceptin

75mg/m2 via i.v. infusion during cycles 1 to 4.

75 mg/m2 via i.v. infusion during cycles 5-8.

500 mg/m2 via i.v. infusion during cycles 5-8.

In the TROIKA study, the proposed biosimilar HD201 will be compared to its reference product Herceptin®. The aim of the study is to demonstrate equivalence of HD201 and Herceptin® in terms of efficacy, safety and pharmacokinetics.

This is a randomised, double-blind, parallel group, equivalence, multicentre Phase III study. 500 patients with HER2+ early breast cancer (EBC) will be randomised (1:1) to receive either HD201 in combination with chemotherapy (n=250) or Herceptin® in combination with chemotherapy (n=250).

HD201 or Herceptin® will be administered every 3 weeks for 8 cycles(24 weeks). After administration of the final neoadjuvant study drug dose, surgery will be done within 3-8 weeks followed by an adjuvant treatment period for 10 cycles.

Patients completing the 18 cycles of treatment and those discontinuing the study will attend an End of Treatment (EOT) visit 4 weeks (+/- 2 days), after last administration of study medication, followed by a follow-up period of 2 years.

Patients will attend study visits every 3 weeks. At each visit, patients will undergo a complete physical examination, vital signs, weight, performance status, clinical laboratory tests and adverse events (AEs), concomitant medication will be recorded. After the EOT visit patients will be followed every 6 months for an additional 24 months or until death, whichever occurs first, to collect data on cardiac safety and disease status.

Cardiac safety will be assessed by echocardiography or multigated acquisition (MUGA) scan to evaluate the left ventricular ejection fraction (LVEF) (at screening, before cycle 5, before surgery, before cycles 12 and 16, EOT visit, and at 6 and 12 months after the completion of trastuzumab (more frequent if necessary)) and by means of a 12-lead ECG (at screening, before cycle 5, before surgery, before cycles 12 and 16, EOT visit, and at 6 and 12 months after the completion of trastuzumab).

The primary efficacy endpoint, total pathological complete response (tpCR) will be assessed at the time of surgery after neoadjuvant treatment completion after 24 weeks. tpCR will be assessed both by local and by central reading.

Sampling for pharmacokinetics (PK) analysis (determination of Ctrough values) will be performed in all patients before cycle 5 and cycle 8.

An Independent Data Monitoring Committee will be implemented that reviews accumulating data of the clinical trial with respect to any potential safety issues, study progress and critical efficacy endpoints. The members will be selected on the basis of relevant experience and understanding of clinical research and the issues specific to the therapeutic area, as well as previous data monitoring committee experience.

A Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in HER2+ Early Breast Cancer Patients

A Randomised, Double-blind, Parallel Group, Equivalence, Multicentre Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in Patients With HER2+ Early Breast Cancer

To compare the total pathological complete response rate (tpCR) in patients treated with HD201 plus chemotherapy to that in patients treated with Herceptin® plus chemotherapy.

To compare total breast pathological complete response rate (bpCR) between the two arms at the time of surgery.

ORR defined as proportion of patients whose best overall response is either complete response (CR) or partial response (PR) at the time of surgery.

OS defined as the time from Day 1 of therapy until death from any cause

EFS defined as the time from Day 1 of therapy (day of first infusion of medication on study) until progression of disease or death from any cause.

Safety and tolerability will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and CTC v4.03

Cardiac dysfunction will be monitored by 12-Lead ECG and measurement of the LVEF by echocardiography or MUGA scan

Incidence of human trastuzumab antibodies

Sampling will be performed in all patients to compare the PK through values of HD201 and Herceptin.

Prestige Biopharma Limited

Digestive System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Stomach Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Stomach Cancer

Esophageal Cancer

16-24 patients per tumour group will be treated with AZD4547 administered 80mg twice daily, 2 weeks on, 1 week off in 21 days cycles.

AZD 4547

Angela Gillbanks

Elizabeth Smyth, MB MRCP MSc

David Cunningham, MD FRCP

Nicholas Turner, MA MRCP PhD

Sanjay Popat, BSc MBBS MRCP PhD

To assess the activity of the FGFR inhibitor AZD4547 in patients with FGFR1 or FGFR2 amplified breast, squamous lung and stomach cancer whose cancers have progressed following previous chemotherapy

Primary endpoint

- To assess anti-tumour activity as change in tumour size at 8 weeks and the correlation with change in tumour ERK1/2 phosphorylation at day 10-14.

Secondary endpoints

* Objective response rate to AZD4547 in all patients and in each tumour group
* Safety and tolerability of AZD4547 in all patients
* Disease control rate at 8 weeks
* Progression free survival in all patients and in each tumour group

Proof-of-Concept Study of AZD4547 in Patients With FGFR1 or FGFR2 Amplified Tumours

A primary objective of the study is to collect serial research biopsies at baseline and on treatment with AZD4547, to assess the molecular changes that occur in the tumour in response to AZD4547 treatment and correlate with change in tumour size assessed at 8 weeks.

Response rate is assessed using RECIST 1.1 radiological response and centrally reviewed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)	NCT04964934	ER-Positive HER...	AZD9833 AZD9833 Placebo Anastrozole Anastrozole pla... Letrozole Letrozole place... Palbociclib Abemaciclib Luteinizing hor... Ribociclib	18 Years - 130 Years	AstraZeneca
A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease	NCT04711252	ER-Positive HER...	AZD9833 Anastrozole Anastrozole pla... AZD9833 placebo Palbociclib Luteinizing hor...	18 Years - 130 Years	AstraZeneca
A Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in HER2+ Early Breast Cancer Patients	NCT03013504	HER2 Positive B...	HD201 Herceptin Docetaxel Epirubicin Cyclophosphamid...	18 Years -	Prestige Biopharma Limited
Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)	NCT04964934	ER-Positive HER...	AZD9833 AZD9833 Placebo Anastrozole Anastrozole pla... Letrozole Letrozole place... Palbociclib Abemaciclib Luteinizing hor... Ribociclib	18 Years - 130 Years	AstraZeneca
A Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in HER2+ Early Breast Cancer Patients	NCT03013504	HER2 Positive B...	HD201 Herceptin Docetaxel Epirubicin Cyclophosphamid...	18 Years -	Prestige Biopharma Limited
Proof-of-Concept Study of AZD4547 in Patients With FGFR1 or FGFR2 Amplified Tumours	NCT01795768	Gastric Cancer Oesophageal Can... Breast Cancer Squamous Cell C...	AZD 4547	25 Years -	Royal Marsden NHS Foundation Trust

Spots Global Cancer Trial Database for multicentre

Every month we try and update this database with for multicentre cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for multicentre

Every month we try and update this database with for multicentre cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for multicentre cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.