the Effect of ABCC2 Genetic Polymorphism on Neurotoxicity in Gastrointestinal Cancer Patients Receiving Oxaliplatin

August 8, 2022 updated by: Sara Mohamed Abdel Aziz Mohamed, Ain Shams University

The Effect of ATP-Binding Cassette C2 (ABCC2) Transporter Genetic Polymorphism on Neurotoxicity in Gastrointestinal Cancer Patients Receiving Oxaliplatin -Based Chemotherapy

Study the effect of genetic polymorphism (rs1885301, rs4148396 and rs3740066) in the membrane of Multidrug resistance protein 2 (MRP2) encoded by ATP-binding cassette C2 (ABCC2) gene and its genetic expression levels on neurotoxicity in gasrtointestinal cancer patients reciving Oxaliplatin-based chemotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Several solutes carriers and ATP-binding cassette transporters have been implicated in the influx or efflux of platinum-based chemotherapeutic agents such as cisplatin, carboplatin, and oxaliplatin. The ATP-binding cassette (ABC-) transporter superfamily contains several family members that may confer intrinsic or acquired multidrug resistance (MDR) by extruding anticancer agents or their metabolites from cells and suppression of such transporters may lead to sensitisation to cytostatic agents. Multidrug resistance protein 2 (MRP2), encoded by the ATP-binding cassette C2 (ABCC2) gene , is an efflux pump located on the apical membrane of many polarized cells, which transports conjugate compounds by an ATP-dependent mechanism like oxaliplatin. Single nucleotide polymorphisms (SNPs) in genes involved in drug transport like ABCC2 gene may lead to higher intracellular oxaliplatin accumulation in the dorsal root ganglia and thus increased risk of Oxaliplatin-induced peripheral neurotoxicity (OXPN). Enhanced ABCC2 expression can lead to decreased cellular glutathione content. Glutathione is needed for oxaliplatin detoxification via conjugation, and it was reported that low glutathione intra- cellular levels can cause increased oxaliplatin cytotoxicity. Moreover, ABCC2 mediates the export of the oxaliplatin-glutathione conjugated form, and ABCC2 overexpressing cells were resistant to platinum derivatives.

Study Type

Observational

Enrollment (Anticipated)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
    • Abassia
      • Cairo, Abassia, Egypt, 11566

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All the pateints presenting to the department of Clinical Oncology Department, Ain Shams University Hospitals with gastrointestinal cancer (stage ≥ stages II ) who receive Oxaliplatin based chemotherapy ( FOLFOX6 ) for adjuvant and metastatic setting.

Description

Inclusion Criteria:

  1. gastrointestinal cancer Patients ( ≥ stages II ) who receive Oxaliplatin based chemotherapy ( FOLFOX6 ) for adjuvant and metastatic setting.
  2. Eastern Cooperative Oncology Group ( ECOG ) performance ≤ 2.
  3. Adequate bone marrow functions ,liver functions and renal functions.

Exclusion Criteria:

  1. Patients who have any clinical neuropathy.
  2. Pateints with Diabetes mellitus.
  3. Serious comorbid systemic disorder incompatible with study.
  4. Pregnancy.
  5. Other primary tumors.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
neurotoxicity
Time Frame: 6 months

the effect of genetic polymorphism (rs1885301, rs4148396 and rs3740066) in the membrane of Multidrug resistance protein 2 (MRP2) encoded by ATP-binding cassette C2 (ABCC2) gene and its genetic expression levels on neurotoxicity in gastrointestinal cancer patients reciving Oxaliplatin-based chemotherapy.

Grading of peripheral neuropathy using National Cancer Institute's Common Toxicity Criteria for Adverse Event ( NCI- CTCAE V5.0 ) will be assessed at baseline and before each cycle.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ain Shams University

Investigators

  • Study Director: Nagwa Ali Sabri, Professor, Clinical Pharmacy Department - Faculty of Pharmacy - Ain Shams University
  • Study Director: May Ahmed Shawki, Lecturer, Clinical Pharmacy Department - Faculty of Pharmacy - Ain Shams University
  • Study Director: Diaa Eldin Moussa Sherif, Lecturer, Clinical oncology and nuclear medicine Department -Faculty of medicine-Ain Shams University
  • Principal Investigator: Sara Mohamed Abdel Aziz, Master Student, Clinical Pharmacy Department - Faculty of Pharmacy - Ain Shams University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 15, 2021

Primary Completion (Actual)

August 5, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

August 5, 2022

First Submitted That Met QC Criteria

August 8, 2022

First Posted (Actual)

August 9, 2022

Study Record Updates

Last Update Posted (Actual)

August 9, 2022

Last Update Submitted That Met QC Criteria

August 8, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 279

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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