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Capecitabine

Patients who experienced severe toxicity (at least one grade 4 side effect) with capecitabine chemotherapy

Patients who experienced dose-limiting toxicity (at least one grade 3, or recurrent grade 2, side effect)with capecitabine chemotherapy

Patients who have experienced low/no toxicity (none or only side effects at grade 1 \& 2) with capecitabine chemotherapy.

Phlebotomy

Vicente Valero, MD

The goal of this laboratory research study is to identify possible differences in a gene among patients with breast cancer that cannot be treated by surgery. Researchers want to find out if differences in this gene may increase the risk of side effects from capecitabine.

If you agree to take part in this study, 1 blood sample (about 2 tablespoons) will be drawn for use in genetic research.

If you are unable to provide a blood sample, researchers will collect leftover tissue samples from your previously collected tumor tissue (from the time of the breast cancer diagnosis). The tumor samples will be used for genetic research.

After the blood draw or tissue collection, your participation in this study will be over.

The blood samples for the genetic research will be stored at Myriad Laboratories. Before your blood and/or tissue is sent to Myriad Laboratories for banking, your name and any personal identifying information will be coded to protect your privacy. M. D. Anderson will not have oversight of any leftover tissue and/or blood that will be banked by Myriad Laboratories for additional research.

This is an investigational study. Up to 210 patients will take part in this study. All will be enrolled at M. D. Anderson.

5 to 7.5 milliliter (mL) sample of blood. Alternatively, DNA will be extracted from 10um slices of formalin-fixed paraffin-embedded tissue from previously collected tumor tissue (from the time of the breast cancer diagnosis).

Association of Dihydropyrimidine Dehydrogenase (DPYD) Variants With Toxicity Related to Capecitabine

A Retrospective Analysis of the Association of Dihydropyrimidine Dehydrogenase (DPYD) Variants With Toxicity Related to Capecitabine

Myrexis Inc.

M.D. Anderson Cancer Center

Irinotecan

This arm will be compiled of prospectively recruited cases for confirmatory testing based on their suspected genotype per Michigan Genomics Initiative and patients who have been retrospectively identified as any patient who had clinical genotype testing and had a variant that was their clinician used to guide the chemotherapy treatment. Prospective patients will undergo confirmatory genetic testing by a CLIA lab and those results will be provided to the patients clinical team at that time.

This arm will be compiled of all retrospective patients where genetic information was not known prior to receiving treatment.

any CLIA certified lab can be used for confirmatory testing after patients have been identified through Michigan Genomics Initiative (MGI)

DPYD or UGT1A1 variants

Cancer AnswerLine

Amy Pasternak

This study will be evaluating patients suspected to carry DPYD or UGT1A1 variants based off of Michigan Genomics Initiative (MGI) results. Standard of care treatment will be initiated with either Fluoropyrimidine or Irinotecan therapy. Retrospective collection of treatment related AEs and SAEs, dose delays, dose reductions, and treatment discontinuations will be completed.

Evaluating a Pharmacogenetic Testing Panel in Patients Suspected to be at Increased Risk for Pharmacogenetics-related AEs While Receiving Fluoropyrimidine or Irinotecan Therapy

Evaluating the Uptake and Impact of a Pharmacogenetic Testing Panel in Patients Suspected to be at Increased Risk for Pharmacogenetics-related AEs While Receiving Fluoropyrimidine or Irinotecan Therapy

Compare rates of grade 3 or higher AEs and SAEs to fluoropyrimidine or irinotecan treatment between subjects with confirmed DPYD or UGT1A1 variants before chemotherapy treatment to retrospective matched controls without confirmatory PGx testing

clinical genotypes and MGI genotypes for participants will be considered concordant if they identify the same DPYD or UGT1A1 variant and discordant if they do not

A decrease in dose of standard of care treatment by \>10% of the dose administered for the prior cycle

Any prolongation of the initiation of the following scheduled treatment cycle due to toxicity as documented by the patient's medical team

Any discontinuation due to clinician-documented toxicity

Evaluation of the amount of new prescriptions written with identified genetic interactions

University of Michigan Rogel Cancer Center

Fluorouracil

Patients of non-Western descent with an indication for treatment with fluoropyrimidine-based chemotherapy. A patient is classified as non-Western if a one (1) of the parents or more than two (\>2) of the grand parents are of non-Western descent.

The DPYD gene of non-Western patients will be sequenced to identify DPYD variants that are possibly associated with an increased risk of developing severe fluoropyrimidine-related toxicity.

Sequencing of DPYD gene

Hans Gelderblom, Prof.

Jesse Swen, PhD

This is a observational, multicenter study to identify novel variants of the DPYD gene which are possible deleterious in patients of non-Western descent.

Research has shown that DPYD-guided dose-individualization based on 4 DPYD variants (DPYD\*2A, c.1236G\>A, c.2846A\>T and c.1679T\>G) can significantly reduce severe fluoropyrimidine-related toxicity. However, these 4 variants are most likely not predictive for toxicity in patients of non-Western descent. In this study the DPYD gene of patients of non-Western descent will be sequenced to identify novel variants that could be associated with a reduced DPD enzyme activity and an increased risk of developing severe fluoropyrimdine-related toxicity. Additionally, the ability to predict if a DPYD variant is possibly deleterious by a recombinant model systen (DPYD-varifier) will be studied.

1. blood sample (whole blood) of 4 ml (EDTA-tube) for sequencing of the DPYD gene
2. blood samples (whole blood) of 6 ml (EDTA-tubes) each for determination of the DPD enzyme activity

Identifying Novel Variants in the DPYD Gene in Patients of Non-Western Descent

A Prospective, Multicenter, Observational Study to Identify Novel Deleterious Variants in the DPYD Gene in Patients of Non-Western Descent: The DPYD-NOW Study

The Netherlands Cancer Institute

Erasmus Medical Center

Haga Hospital

Medical Center Haaglanden

Leiden University Medical Center

Prof. dr.

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antimetabolites

Patients were included in this arm if they have digestive cancer and an uracil dosage \<16 ng/mL performed between February 2018 to January 2020, and if they received at least one cycle of fluoropyrimidine-based chemotherapy in one of the four oncology departments (Hopital Edouard Heriot \[Lyon\], Centre Hospitalier de Lyon Sud \[Lyon\], Hopital de la Croix Rousse \[Lyon\].

In each group with an uracil dosage; at cycle 1; capecitabine or continuous 5-FU dose percentage will be evaluate retrospectively in our database

Fluoropyrimidine treatment (5-FU or capecitabine) and dosage

For each patient, uracil concentration will be evaluate and patients will be compared based on 16 ng/mL as threshold.

Uracil dosage

For each group of patient, on 16 ng/mL as threshold for uracil concentration, overall survival will be compared betwen the two groups of patients (Uracil \<16 vs Uracil ≥16).

Overall survival

Digestive carcinomas chemotherapies regimen are mostly based on fluoropyrimidine drugs (5-Fluorouracil (5-FU) or capecitabine). 5-FU is mainly catabolised by dihydropyrimidine dehydrogenase (DPD) and partial or complete DPD deficiency can cause severe adverse reactions. Different strategies have been proposed to predict DPD deficiency; the two main approaches are phenotyping the enzyme activity (directly or indirectly), or genotyping the four main polymorphisms associated with 5-FU-toxicity. In February 2018, the French medicines agency (Agence nationale de sécurité du médicament et des produits de santé, ANSM) recommended DPD genotyping for all patients receiving fluoropyrimidine-based treatment to improve its safety as compared to the European Medicines Agency (EMA)13 and others pharmacogenetics working group.

In December 2018, a new guideline from the French cancer institute (Institut National Du Cancer, INCa) and the French health authority (Haute Autorité de Santé, HAS) recommended the measurement of the uracil blood level before genotyping DPD and dose adaptation if this level is greater than 16 ng/mL. The aim herein is to assess how this recommendation has been implemented in clinical routine. 5-FU displays a dose-response relationship regarding both its efficacy and its toxicity, did tailored-dose impair the treatment efficacy as it decreased the risk of toxicity? To address that matter we conducted a retrospective study to evaluate how fluoropyrimidine dosage is adapted to uracil concentration with an emphasis on how patients outcome were affected. We compared time to failure and overall survival between patients with an uracil concentration \< 16 ng/mL and \> or = 16 ng/mL.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Association of Dihydropyrimidine Dehydrogenase (DPYD) Variants With Toxicity Related to Capecitabine	NCT00478686	Breast Cancer	Phlebotomy	-	M.D. Anderson Cancer Center
Evaluating a Pharmacogenetic Testing Panel in Patients Suspected to be at Increased Risk for Pharmacogenetics-related AEs While Receiving Fluoropyrimidine or Irinotecan Therapy	NCT05583422	Cancer	DPYD or UGT1A1 ...	18 Years -	University of Michigan Rogel Cancer Center
Association of Dihydropyrimidine Dehydrogenase (DPYD) Variants With Toxicity Related to Capecitabine	NCT00478686	Breast Cancer	Phlebotomy	-	M.D. Anderson Cancer Center
Identifying Novel Variants in the DPYD Gene in Patients of Non-Western Descent	NCT04300361	Neoplasms	Sequencing of D...	18 Years -	Leiden University Medical Center
Evaluating a Pharmacogenetic Testing Panel in Patients Suspected to be at Increased Risk for Pharmacogenetics-related AEs While Receiving Fluoropyrimidine or Irinotecan Therapy	NCT05583422	Cancer	DPYD or UGT1A1 ...	18 Years -	University of Michigan Rogel Cancer Center
Fluoropyrimidine Tailored-dose Based on Uracil Concentration in Patients Treated for Digestive Carcinomas: Evaluation of Clinical Practice	NCT04918264	Digestive Carci...	Fluoropyrimidin... Uracil dosage Overall surviva...	18 Years -	Hospices Civils de Lyon
Evaluating a Pharmacogenetic Testing Panel in Patients Suspected to be at Increased Risk for Pharmacogenetics-related AEs While Receiving Fluoropyrimidine or Irinotecan Therapy	NCT05583422	Cancer	DPYD or UGT1A1 ...	18 Years -	University of Michigan Rogel Cancer Center

Spots Global Cancer Trial Database for dpyd

Every month we try and update this database with for dpyd 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 dpyd

Every month we try and update this database with for dpyd 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 dpyd 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.