A pharmacogenomic (PGx) panel will be performed to test for genetic variations in genes related to drug response.

Patients undergoing hematopoietic stem cell transplantation will be genotyped and supportive care therapies tailored to identified drug-gene pairs and guideline recommendations

Pharmacogenomic-guided supportive care

Justin R Arnall, PharmD

Hematopoietic cell transplantation (HCT) is the only curative treatment modality for many hematologic malignancies. Morbidity and mortality rates have declined drastically over the years, secondary to improvements in both transplant techniques and pharmacotherapies, including immunosuppressants, anti-infectives, analgesics and other supportive care medications. Despite advances in patient care, toxicities associated with HCT (e.g., graft-versus-host disease (GVHD), infection, pain, anxiety, depression, mucositis, nausea/vomiting) continue to pose challenges in patient care and have a significant impact on quality of life. (QOL). A recent study demonstrated subjects randomized to intensive supportive care had a clinically significant improvement in their QOL during hospitalization and up to 3 months post-transplant compared to those receiving standard care.

Further follow up evaluations have evaluated the impact of focused palliative care/symptom management on QOL metrics - inclusive of Edmonton Symptom Assessment surveys (ESAS). In other malignant settings, i.e. solid tumor, ESAS has been noted as an effective measure of symptoms control and the utilization of this assessment is linked to positive outcomes. The American Society of Clinical Oncology (ASCO) has designated QOL as the second most relevant metric for post-transplant patient care behind survival, making the optimization of supportive care pharmacotherapy a clinically relevant subject to investigate. Pharmacogenetics (PGx) uses an individual's genetic factors, such as single nucleotide polymorphisms (SNPs), to personalize therapy or dose selection. SNPs encode drug-metabolizing enzymes, transporters, and targets that can significantly impact drug efficacy and toxicity. With the growing complexity of both antineoplastics and supportive care, oncologists have less time to manage each subject's myriad of supportive care concerns by trial and error. Suboptimal management of symptoms compromises potential benefits from cancer therapy, disrupts clinic workflow, increases emergency room visits, and affects both patient satisfaction and reimbursement. Genetic variation is well documented across the human genome and affects a subject's response to medications regarding efficacy and toxicity. The genome is quickly becoming a pragmatic tool that can assist oncologists and other providers in optimizing supportive care for subjects with cancer.

The investigators hypothesize that the implementation of a pharmacist-driven precision medicine service guided by HCT clinical pharmacists and Specialty Pharmacy pharmacists using preemptive pharmacogenomic (PGx) testing will identify drug-gene interactions relevant to the supportive care of HCT subjects. This approach to care may improve symptom management and QOL as interpreted via ESAS in adult HCT subjects treated at our institution. With the experience of past studies and a customized genetic panel, the investigators will genotype subjects prior to transplant and identify actionable drug-gene pairs and utilize these to direct supportive therapies. To date no studies have highlighted the significance of incorporating preemptive PGx testing to personalize therapy selection and dosing into the management of adult HCT subjects as a means of improving QOL and symptom management. The primary aim is to estimate the frequency of subjects undergoing PGx testing who receive at least one drug/dose selection or modification based on their test results during the study period (from admission for HCT to HCT D100). Secondarily the investigators will measure improvement in aggregate and individual scores on the ESAS survey and will further use the ESAS in its totality to assess the impact of PGx-guided care as compared to pre-implementation/non-PGx driven strategies through aggregate ESAS scores, individual ESAS scores, and differences between HCT admission (or baseline) and HCT Day 30 scores before and after the intervening program. In the outpatient setting the investigators will utilize planned medication reconciliation (with PGx guidance) by Specialty Pharmacy Service pharmacists to adhere to PGx-recommendations and capture insight into the implementation of this program to share with other practitioners. The implementation of this study will personalize pharmacotherapy, improve symptom management and QOL in adult HCT subjects treated at our institution, and offer guidance globally in supporting the role of the pharmacist in pharmacogenomics (PGx) and management of HCT subjects.

This will be a prospective, pre/post interventional, single arm study

Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation

A Prospective Interventional Trial of Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation

All data and records generated during this study will be kept confidential in accordance with Institutional policies on subject privacy and HIPAA and that the investigator and other site personnel will not use such data and records for any purpose other than conducting the study. We do not anticipate any breach of confidentiality as no records will be shared with any personnel outside the research team. All medical information will be recorded and stored in a database. The database will exist on a password protected secured server. Medical records data will be abstracted by the Research Designee. All records will be kept confidential.

The primary objective is to estimate the frequency of subjects undergoing PGx testing who receive at least one drug/dose selection or modification based on their test results during the study period

Determine if PGx-guided supportive care is associated with changes in symptom management following HCT compared to control data attained from subjects not consenting to PGx testing, as assessed by individual and aggregate Edmonton Symptom Assessment Scale (ESAS) scores as well as their changes in ESAS scores (ESAS being an 11-point symptoms assessment with low scores associated with low symptom burden and the high scores associated with significant burden)

Describe longitudinal changes in individual and aggregate Edmonton Symptom Assessment Scale (ESAS) scores as indicative of QOL (ESAS being an 11-point symptoms assessment with low scores associated with low symptom burden and the high scores associated with significant burden)

Among the PGx-guided supportive care subjects, investigators will assess the type and frequency of actionable genetic polymorphisms observed in the evaluable population and in the subset that received a drug and/or dose selection/modification based on PGx results

Wake Forest University Health Sciences

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Chritian Brambilla, Pr.

The purpose of this study is to correlate molecular genetic profile with response to chemotherapy in case of primary chemotherapy treatment for non-small cells lung carcinoma.

Lung carcinoma will be the fifth death cause in the world in 2020. In Europe it causes more deaths than carcinoma of breast, colon and prostate combined so it is a public healthcare priority. Applying high throughput molecular analysis technologies to pharmacogenomics could improve lung carcinoma care strategies. The study hypothesis is that the determination of the genomic and proteomic profiles of non-small cell lung carcinoma patients will allow treatment targeting , improving treatment efficacy and tolerance.

In order to carry out this study, the five thoracic oncology centers of the Rhône-Alpes region will collaborate with several INSERM (French national research institute) units and new biotechnology companies.

The primary objective of this study is to correlate molecular genetic profile with response to chemotherapy in cases of primary chemotherapy treatment for non-small cell lung carcinomas.

Biological samples will be collected before and during patient care to correlate clinical evolution (response and tolerance) with:

* circulating cell polymorphism profile
* proteomic profile
* genetic and epigenetic modifications of genes involved in DNA repair, drugs metabolism, apoptosis cell regulation mechanisms, and cell mobility and adhesion mechanisms.

The main judgment criteria will be response to chemotherapy correlated with patient's biological profile.

Second judgment criteria will be overall survival and hematology toxicity which will be evaluated each new cycle of chemotherapy.

The second purpose of this study is to validate less invasive methods of sampling using blood, expectoration, urine, fixed biopsies and lungs tapping, as a substitute to the current reference (frozen tumor), which is out of reach in clinical examination.

This will contribute to setting of a multicentric resources bank, to define targets for new drugs and to develop oligoarrays allowing adapted chemotherapies.

Two previous studies (1800 and 500 patients respectively) have already been carried out, data and samples are available.

For this study, 600 patients will be included over 3 years.

Pharmacogenomic Study Realized on "Non-small Cell Lung Carcinoma"

Pharmacogenomic Study Realized Within the Framework of the Common Care to "Non-small Cell Lung Carcinoma" at Any Stages Treated by Chemotherapy.

Ministry of Health, France

University Hospital, Grenoble

University Hospital of Grenoble

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Sangmyung Woo

1. Based on the literature, the pancreatic cancer treatment predictor biomarker, which is used in the domestic clinical field, is actually applied to the pancreatic cancer patient cohort of the National Cancer Center.
2. To systematically prospectively identify prospective treatment response biomarkers for Pancreatic Cancer Cohort in the National Cancer Center

1. Immunohistochemistry and gene test for hENT1, DCK, SMAD4, CES2, BRCA 1/2,PALB2, MMRd, MSI, Tumor Ag and etc. on Cancer sample
2. Collect data of Biomarker for pancreatic cancer
3. Compare with Big data and Cohort study in National cancer center
4. The number of subjects is changed by statistical consideration. 218-\>238

A Longitudinal, Observational Biomarker Study in Pancreatic Cancer Patients Receiving Chemotherapy

The length of time from either the date of diagnosis or the start of treatment for a disease,the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse

The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse

National Cancer Center, Korea

Chief, Senior Scientist

Substance Related Disorders

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Standard of Care prescribing for period of 12 months. Participants will receive pharmacogenomic test results according to the current standard of care. The participants will be followed up for a minimum of 12 weeks, with maximal time-period being 12 months depending on time of enrolment.

Extended Pharmacogenomic prescribing for a period of 12 months. Participants will receive pharmacogenomic testing across a range of clinically relevant variants, to guide the dose and drug selection of 27 drugs commonly used in supportive care. The participants will be followed up for a minimum of 12 weeks, with maximal time-period being 12 months depending on time of enrolment.

Whole genome sequencing with reporting on current standard of care (SoC) pharmacogenomic variants (TPMT, NUD15) where applicable (i.e, for patients with diagnosis of acute lymphoblastic leukaemia) by Week 1. Whole genome sequencing on a broader number of actionable variants as per international guidelines for cancer supportive care (identical to study arm) will be reported on at Week 13.

Release of Extended Pharmacogenomics Report at Week 1

Whole genome sequencing with reporting on current standard of care (SoC) pharmacogenomic variants (TPMT, NUD15) where applicable (i.e, for patients with diagnosis of acute lymphoblastic leukaemia) and reporting of a broader number of actionable pharmacogenomic variants as per international guidelines for cancer supportive care reported on by Week 1.

Release of Extended Pharmacogenomics Report at Week 13

Tayla Stenta

Claire Moore

Dr. Marion Mateos

Dr Sophie Jessop

A/Prof Rachel Conyers

A/Prof Rishi Kotecha

A prospective, open, randomised implementation study in paediatric cancer patients. The study aims to determine whether a personalised approach will result in an overall reduction in clinically relevant adverse drug reactions (ADRs) and to evaluate the economic and quality of life impacts. Participants will be randomised to receive personalised guided prescribing of supportive care therapy (study arm) or standard of care (control arm) for a period of 12 weeks. The follow up period includes prospective patient reporting of symptoms and quality of life through electronically delivered surveys, for a maximum of 12 months.

One of the main areas of precision medicine that is easily implementable is pharmacogenomic testing. Germline testing of genes predisposing to drug toxicity or inefficacy can inform drug selection and dosing. This steers away from the historical 'trial and error' approach, avoids unnecessary adverse drug reactions (ADRs) and can potentially impact on health economic savings, through reduction in readmissions and admissions with ADRs.

This study will be a prospective, open, randomised implementation study in paediatric and adolescent patients with a new diagnosis of cancer or who are proceeding to first haematopoietic stem cell transplantation (HSCT). The current standard of care for paediatrics in Australia involves pharmacogenomic testing for TPMT and NUD15, for patients with acute lymphoblastic leukaemia. Participants of the study will receive pharmacogenomic testing across a range of clinically relevant variants. Participants will be randomised to either the control arm or the study arm. Test results for participants in the study arm will be used to guide the dose and drug selection of 27 drugs commonly used in supportive care. The pharmacogenomic test results will be released to the study arm at week 4 and to the control arm at week 13, after the 12 week intervention period.

To determine whether pre-emptive pharmacogenomic testing does reduce clinically relevant adverse drug reactions, the Paediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE) survey will be delivered at 3 time points within a 12 week period. This survey is a patient reported outcome measurement tool developed to evaluate symptomatic toxicity in participants receiving cancer therapy. After survey completion, semi-structured interviews will be conducted by an academic pharmacist with the aim of generating a CTCAE grade of severity for each of the symptoms defined in the Ped-PRO-CTCAE and assessing the causality of an adverse drug reaction using the Liverpool Adverse Drug Reaction Causality Assessment Tool (Liverpool ADR-CAT). These mechanisms will support the assessment of both severity and causality of any adverse drug reactions.

To evaluate the economic and Quality of Life impacts (QoL), participants will also complete The Child Health Utility 9D (CHU9D) QoL surveys specific to children and young adults at 3 timepoints over the 12-month period and consent to a Health Economics Analysis. This includes collection of Medicare Benefits Schedule (MBS)/ Pharmaceutical Benefits Scheme (PBS) data from Services Australia and Victorian Data Linkage Group to compare the costs of management of both the control and study arm.

Data from the study will be securely stored on the REDCap database. Patients will be allocated a unique patient identifier prior to their de-identified data being added to the database.

Minimising Adverse Drug Reactions and Verifying Economic Legitimacy in Children (MARVEL-PIC)

Minimising Adverse Drug Reactions and Verifying Economic Legitimacy - Pharmacogenomics Implementation in Children (MARVEL-PIC)

The de-identified data set collected for this analysis of the study will be available from 6 months after publication of the primary outcome. Only de-identified data will published. The study protocol, analysis plan and consent forms will also be available. The data may be obtained from the Murdoch Children's Research Institute by emailing MCTC@mcri.edu.au.

The primary outcome is a reduction in adverse drug reactions among patients with actionable pharmacogenomic variants. An adverse drug reaction will be considered as any CTCAE grade 2 and above for non-haematological toxicities or CTCAE grade 3 and above for haematological toxicities. CTCAE grades are defined as 1,2,3,4 or 5, with 5 indicating the most severe.

An adverse drug reaction will be considered as any CTCAE grade 2 and above for non-haematological toxicities or CTCAE grade 3 and above for haematological toxicities. This includes an ADR which was caused either by the index drug of inclusion or any subsequent drug. CTCAE grades are defined as 1,2,3,4 or 5, with 5 indicated the most severe.

The Liverpool ADR CAT is an assessment tool produced to attribute causality to specific drugs for the grading of ADR symptomatic toxicity. Possible grading of ADRs include either definite, probable or possible.

The Ped-PRO-CTCAE survey is an electronic patient reported outcome measurement survey developed to evaluate symptomatic toxicity in patients who are receiving cancer therapy. Symptoms are evaluated for attributes of frequency, severity, interference, amount, presence or absence. Each symptomatic adverse event (AE) is assessed by 1-3 attributes that can be linked back to a CTCAE grade. The number of self-reported ADRs are measured independent of severity or drug-gene association but caused by one of the chemotherapeutic /targeted agents.

The Ped-PRO-CTCAE survey is an electronic patient reported outcome measurement survey developed to evaluate symptomatic toxicity in patients who are receiving cancer therapy. Symptoms are evaluated for attributes of frequency, severity, interference, amount, presence or absence. Each symptomatic adverse event (AE) is assessed by 1-3 attributes that can be linked back to a CTCAE grade. The number of self-reported ADRs are measured independent of severity or drug-gene association but caused by one of the chemotherapeutic /targeted agents. An ADR will be classified as serious if that event led to death, serious deterioration in health, or fetal distress.

Number of dose adjustments made to drug-gene associated therapy during the entire study follow up by review of the participants electronic medical record and medication reconciliation.

Incidence of drug cessation due to ADR during the entire study follow up. Relates to inclusion criteria drug by review of the participants electronic medical record and medication reconciliation.

Incidence of drug cessation due to lack of efficacy by review of the participants electronic medical record and medication reconciliation.

Therapeutic drug monitoring (routine drug levels) performed during entire study follow up period by review of the participants electronic medical record and medication reconciliation.

After discussion and consensus of a pharmacogenetic variant. A clinical report will be generated with the results and therapeutic recommendations according to Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Adherence to recommendations will be reported with reasoning, during the 12 week period.

Data will be collected on the costs of management comparing the standard of care arm versus the study arm. The actual costs assigned to each inpatient or outpatient episode will be collected. This information is readily accessible through Services Australia and The Department of Health via The Centre for Victorian Data Linkage (CVDL).

The University of Sheffield CHU9D Quality of Life Survey will be used to monitor changes in patient QoL. The CHU9D consists of a descriptive system and set of preference weights, for 9 questions that assess participants daily functioning across the following domains: worry, sadness, pain, tiredness, annoyance, school, sleep, daily routine and activities. The tool allows for calculation of quality adjusted life years for use in cost utility analysis

Murdoch Childrens Research Institute

Stomach Neoplasms

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide

Carbonic Anhydrase Inhibitors

Enzyme Inhibitors

E7070

Tatsuo Watanabe

Phase I study:

To investigate primary objective (maximal tolerated dose and dose-limiting toxicity) and secondary objectives (pharmacokinetics, safety, estimation of a recommended dose, and anti-tumor effect by evaluable case) of E7070 in patients with gastric cancer who are extensive or intermediate metabolizer type (EM/IM) to CYP2C9 and CYP2C9 by intravenously administering once every 3 weeks.

Phase IIa study:

To investigate primary objective (response rate for efficacy assessment) and secondary objectives (frequency and severity of adverse drug reactions, and pharmacokinetics) of E7070 in patient with gastric cancer who are EM/IM type by intravenously administering once every 3 weeks.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pharmacogenomic-Guided Supportive Care in Hematopoietic Cell Transplantation	NCT04727827	Hematopoietic C... Oncology	Pharmacogenomic...	18 Years -	Wake Forest University Health Sciences
Pharmacogenomic Study Realized on "Non-small Cell Lung Carcinoma"	NCT00222404	Carcinoma, Non-...		18 Years -	University Hospital, Grenoble
A Longitudinal, Observational Biomarker Study in Pancreatic Cancer Patients Receiving Chemotherapy	NCT04281511	Pancreatic Canc...		-	National Cancer Center, Korea
Minimising Adverse Drug Reactions and Verifying Economic Legitimacy in Children (MARVEL-PIC)	NCT05667766	Neoplasms Bone Marrow Tra...	Release of Exte... Release of Exte...	- 18 Years	Murdoch Childrens Research Institute
A Study of E7070 in Patients With Gastric Cancer	NCT00165594	Gastric Cancer	E7070	20 Years - 74 Years	Eisai Inc.
Pharmacogenomic Study Realized on "Non-small Cell Lung Carcinoma"	NCT00222404	Carcinoma, Non-...		18 Years -	University Hospital, Grenoble

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