NCT05093023

Brief Summary

The study aim is to determine the allele frequencies of 1236 G\>A and 3435 G\>A in ABCB1 and study their association with the incidence and severity of paclitaxel-induced peripheral neuropathy while adjusting for other baseline covariates in Egyptian patients. Additionally, the study aimed at fitting and validating logistic regression models with the aforementioned SNPs evaluated in additive, dominant, overdominant, and recessive genetic models and performing diagnostics for the best model in terms of internal validity.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
92

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Mar 2018

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2018

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2020

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2020

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

October 13, 2021

Completed
13 days until next milestone

First Posted

Study publicly available on registry

October 26, 2021

Completed
Last Updated

October 26, 2021

Status Verified

October 1, 2021

Enrollment Period

1.8 years

First QC Date

October 13, 2021

Last Update Submit

October 13, 2021

Conditions

Paclitaxel Adverse ReactionNeuropathy;PeripheralBreast Cancer

Outcome Measures

Primary Outcomes (1)

  • Grade 2 or higher peripheral neuropathy

    Grade 2 or higher peripheral neuropathy evaluated by the National Cancer Institute Common Toxicity Criteria (version 5.0)

    12 weeks

Interventions

Real-Time PCRGENETIC

Genomic DNA was extracted from 2 ml of venous blood. ABCB1 1236 G\>A and 3435 G\>A were genotyped using predesigned TaqMan SNP genotyping assays on a stepOne PCR instrument in accordance with the manufacturer's protocol.

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Egyptian women with histologically confirmed Breast Cancer, receiving neoadjuvant and/or adjuvant weekly paclitaxel-containing regimens.

You may qualify if:

  • Egyptian females ≥18 years of age.
  • Histologically confirmed Breast Cancer.
  • Receiving conventional neoadjuvant or adjuvant weekly paclitaxel.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Adequate organ reserves ((serum creatinine ≤1.5x upper normal limit (UNL), total bilirubin ≤1.5x UNL, absolute neutrophil count ≥1.5 x 10\^9/L, platelet count ≥100 x 10\^9/L, AST and ALT ≤3.0x UNL, and alkaline phosphatase ≤3.0x UNL).
  • No major neurological disease or symptoms prior to the start of paclitaxel therapy.
  • neither subjective nor objective evidence of metastatic disease.

You may not qualify if:

  • Pregnancy.
  • Patients with recurrent or metastatic (local or distant) breast cancer.
  • Neuropathic at the time of recruitment.
  • History of neuropathy prior to recruitment.
  • Previously exposed to taxanes or any other microtubule Inhibitors, or regimens including platinates.
  • Patients currently receiving dose-dense biweekly taxane-containing regimens.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Nasser's Institute Hospital

Cairo, Aghakhan, Egypt

Location

Related Publications (9)

  • Green H, Soderkvist P, Rosenberg P, Mirghani RA, Rymark P, Lundqvist EA, Peterson C. Pharmacogenetic studies of Paclitaxel in the treatment of ovarian cancer. Basic Clin Pharmacol Toxicol. 2009 Feb;104(2):130-7. doi: 10.1111/j.1742-7843.2008.00351.x. Epub 2008 Dec 16.

    PMID: 19143748BACKGROUND

  • Kimchi-Sarfaty C, Marple AH, Shinar S, Kimchi AM, Scavo D, Roma MI, Kim IW, Jones A, Arora M, Gribar J, Gurwitz D, Gottesman MM. Ethnicity-related polymorphisms and haplotypes in the human ABCB1 gene. Pharmacogenomics. 2007 Jan;8(1):29-39. doi: 10.2217/14622416.8.1.29.

    PMID: 17187507BACKGROUND

  • Rivera E, Cianfrocca M. Overview of neuropathy associated with taxanes for the treatment of metastatic breast cancer. Cancer Chemother Pharmacol. 2015 Apr;75(4):659-70. doi: 10.1007/s00280-014-2607-5. Epub 2015 Jan 18.

    PMID: 25596818BACKGROUND

  • Scripture CD, Figg WD, Sparreboom A. Peripheral neuropathy induced by paclitaxel: recent insights and future perspectives. Curr Neuropharmacol. 2006 Apr;4(2):165-72. doi: 10.2174/157015906776359568.

    PMID: 18615126BACKGROUND

  • Gao B, Russell A, Beesley J, Chen XQ, Healey S, Henderson M, Wong M, Emmanuel C, Galletta L, Johnatty SE, Bowtell D; Australian Ovarian Cancer Study Group; Haber M, Norris M, Harnett P, Chenevix-Trench G, Balleine RL, deFazio A. Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer. Sci Rep. 2014 May 9;4:4669. doi: 10.1038/srep04669.

    PMID: 24810093BACKGROUND

  • Sparreboom A, van Tellingen O, Nooijen WJ, Beijnen JH. Preclinical pharmacokinetics of paclitaxel and docetaxel. Anticancer Drugs. 1998 Jan;9(1):1-17. doi: 10.1097/00001813-199801000-00001.

    PMID: 9491787BACKGROUND

  • Wolking S, Schaeffeler E, Lerche H, Schwab M, Nies AT. Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature. Clin Pharmacokinet. 2015 Jul;54(7):709-35. doi: 10.1007/s40262-015-0267-1.

    PMID: 25860377BACKGROUND

  • Tulsyan S, Mittal RD, Mittal B. The effect of ABCB1 polymorphisms on the outcome of breast cancer treatment. Pharmgenomics Pers Med. 2016 Apr 27;9:47-58. doi: 10.2147/PGPM.S86672. eCollection 2016.

    PMID: 27175090BACKGROUND

  • Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Nat Rev Neurol. 2010 Dec;6(12):657-66. doi: 10.1038/nrneurol.2010.160. Epub 2010 Nov 9.

    PMID: 21060341BACKGROUND

MeSH Terms

Conditions

NeuritisBreast Neoplasms

Interventions

Real-Time Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Peripheral Nervous System DiseasesNeuromuscular DiseasesNervous System DiseasesNeoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Polymerase Chain ReactionNucleic Acid Amplification TechniquesGenetic TechniquesInvestigative Techniques

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Master's Student

Study Record Dates

First Submitted

October 13, 2021

First Posted

October 26, 2021

Study Start

March 1, 2018

Primary Completion

January 1, 2020

Study Completion

January 31, 2020

Last Updated

October 26, 2021

Record last verified: 2021-10

Locations

EG(1)