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AzTrials

Gastrointestinal CancerNCT05494320

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

An observational study of Gastrointestinal Cancer, run by Ain Shams University at 1 site in Egypt.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastrointestinal Cancer
What is being tested?
Folfox Protocol
How many people
120 participants
Where
1 siteEgypt
Study dates
15 Aug 2021to 31 Dec 2022
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

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

Who cannot join

  • Patients who have any clinical neuropathy.
  • Pateints with Diabetes mellitus.
  • Serious comorbid systemic disorder incompatible with study.
  • Pregnancy.
  • Other primary tumors.

Trial locations and contacts

1 site in 1 country.

Sara Mohamed Abdel Aziz, Master Student contact

00201119215516

dr.sara.mohamed75@gmail.com

May Ahmed Shawki, Lecturer contact

00201001701461

mannus.ahmed@yahoo.com

Egypt1 site, 1 recruiting

  • Ain shams university

    Cairo, Abassia, 11566

    Sara Mohamed Abdel Aziz, 00201119215516, dr.sara.mohamed75@gmail.com

    Recruiting

Other trials in Egypt

About this study

Official title: 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.

Read the 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.

Being tested
Folfox Protocol
Keywords
neurotoxicity, oxaliplatin, genetic polymorphism
Medical subject headings
Gastrointestinal Neoplasms, Neurotoxicity Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Folfox ProtocolDrug

    Also called Folfox_6

    Folfox: It includes the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. neurotoxicity

    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.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2022
  2. Study start15 Aug 2021
  3. Primary completion5 Aug 2022
  4. Study completion31 Dec 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05494320
Sponsor's protocol ID
279
Status last verified
Aug 2022
First submitted
5 Aug 2022
Last updated
9 Aug 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Alberti P, Rossi E, Cornblath DR, Merkies IS, Postma TJ, Frigeni B, Bruna J, Velasco R, Argyriou AA, Kalofonos HP, Psimaras D, Ricard D, Pace A, Galie E, Briani C, Dalla Torre C, Faber CG, Lalisang RI, Boogerd W, Brandsma D, Koeppen S, Hense J, Storey D, Kerrigan S, Schenone A, Fabbri S, Valsecchi MG, Cavaletti G; CI-PeriNomS Group. Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin. Ann Oncol. 2014 Jan;25(1):257-64. doi: 10.1093/annonc/mdt409. Epub 2013 Nov 19.

    PubMed 24256846

  • Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009 Jul 1;27(19):3109-16. doi: 10.1200/JCO.2008.20.6771. Epub 2009 May 18.

    PubMed 19451431

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

    PubMed 30207593

  • Cappell MS. Pathophysiology, clinical presentation, and management of colon cancer. Gastroenterol Clin North Am. 2008 Mar;37(1):1-24, v. doi: 10.1016/j.gtc.2007.12.002.

    PubMed 18313537

  • Cecchin E, D'Andrea M, Lonardi S, Zanusso C, Pella N, Errante D, De Mattia E, Polesel J, Innocenti F, Toffoli G. A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen. Pharmacogenomics J. 2013 Oct;13(5):403-9. doi: 10.1038/tpj.2012.31. Epub 2012 Aug 7.

    PubMed 22868256

  • Ewertz M, Qvortrup C, Eckhoff L. Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and platinum derivatives. Acta Oncol. 2015 May;54(5):587-91. doi: 10.3109/0284186X.2014.995775. Epub 2015 Mar 9.

    PubMed 25751757

  • Grady WM, Markowitz SD. The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening. Dig Dis Sci. 2015 Mar;60(3):762-72. doi: 10.1007/s10620-014-3444-4. Epub 2014 Dec 10.

    PubMed 25492499

  • Nichetti F, Falvella FS, Miceli R, Cheli S, Gaetano R, Fuca G, Infante G, Martinetti A, Antoniotti C, Falcone A, Di Bartolomeo M, Cremolini C, de Braud F, Pietrantonio F. Is a pharmacogenomic panel useful to estimate the risk of oxaliplatin-related neurotoxicity in colorectal cancer patients? Pharmacogenomics J. 2019 Oct;19(5):465-472. doi: 10.1038/s41397-019-0078-0. Epub 2019 Feb 4.

    PubMed 30713338

  • Mirakhorli M, Rahman SA, Abdullah S, Vakili M, Rozafzon R, Khoshzaban A. Multidrug resistance protein 2 genetic polymorphism and colorectal cancer recurrence in patients receiving adjuvant FOLFOX-4 chemotherapy. Mol Med Rep. 2013 Feb;7(2):613-7. doi: 10.3892/mmr.2012.1226. Epub 2012 Dec 7.

    PubMed 23232902

  • Nguyen TQ, Bui TO, Tran PT, Tran VT, Nguyen VH, Chu QH, Bui TAT, Le NQ, Le VQ, Dao VT. Modified Folfox6 as Adjuvant Chemotherapy in Vietnamese Patients With Colorectal Cancer. Cancer Control. 2019 Jan-Dec;26(1):1073274819864111. doi: 10.1177/1073274819864111.

    PubMed 31317770

Questions about this trial

What is this clinical trial studying?

An observational study of Gastrointestinal Cancer, run by Ain Shams University at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Sara Mohamed Abdel Aziz, Master Student (00201119215516, dr.sara.mohamed75@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

neurotoxicity (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05494320, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2022.

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