ABCB1 SNPs as Predictors of PIPN

Breast Cancer Clinical Trial

Official title:

ABCB1 Single Nucleotide Polymorphism Genotypes as Predictors of Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05093023
• Other study ID #: ABCB1 in Paclitaxel Neuropathy
• Status: Completed
• Start date: March 1, 2018
• Est. completion date: January 31, 2020

Study information

• Verified date: October 2021
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: January 31, 2020
• Est. primary completion date: January 1, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Egyptian females =18 years of age.

2. Histologically confirmed Breast Cancer.

3. Receiving conventional neoadjuvant or adjuvant weekly paclitaxel.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

5. 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).

6. No major neurological disease or symptoms prior to the start of paclitaxel therapy.

7. neither subjective nor objective evidence of metastatic disease.

Exclusion Criteria:

1. Pregnancy.

2. Patients with recurrent or metastatic (local or distant) breast cancer.

3. Neuropathic at the time of recruitment.

4. History of neuropathy prior to recruitment.

5. Previously exposed to taxanes or any other microtubule Inhibitors, or regimens including platinates.

6. Patients currently receiving dose-dense biweekly taxane-containing regimens.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Neuropathy;Peripheral
• Paclitaxel Adverse Reaction
• Peripheral Nervous System Diseases

Intervention

Genetic:
• Real-Time PCR
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.

Locations

Country	Name	City	State
Egypt	Nasser's Institute Hospital	Cairo	Aghakhan

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (9)

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. Review. — View Citation

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. — View Citation

Gréen H, Söderkvist 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. — View Citation

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. — View Citation

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. Review. — View Citation

Scripture CD, Figg WD, Sparreboom A. Peripheral neuropathy induced by paclitaxel: recent insights and future perspectives. Curr Neuropharmacol. 2006 Apr;4(2):165-72. — View Citation

Sparreboom A, van Tellingen O, Nooijen WJ, Beijnen JH. Preclinical pharmacokinetics of paclitaxel and docetaxel. Anticancer Drugs. 1998 Jan;9(1):1-17. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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