Desloratadine to Prevent Taxane-induced Peripheral Neuropathy in Patients With Breast Cancer

NCT07109817 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2025-16651
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blinded randomized controlled clinical trial that aims to study if desloratadine can reduce rates of peripheral neuropathy development in patients with breast cancer receiving taxane chemotherapy. Researchers will compare desloratadine to a placebo (look-alike substance with no drug) and use validated neurotoxicity and quality of life questionnaires to determine if desloratadine can be used to prevent or make taxane induced peripheral neuropathy (TPIN) symptoms better.

Conditions

Breast Cancer; Peripheral Neuropathy

Keywords

Patient reported outcomes; Biomarkers; Taxane; Neuroinflammatory; Cytokine

Outcome Measures

Primary Outcomes (1)

• Change in Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG)-Neurotoxicity (NTX) Subscale Version 4 (FACT-GOG-NTX) neuropathy score

  The patient-related-outcome based neurotoxicity will be assessed using the 11 items about neurotoxicity in the FACT/GOG-NTX questionnaire. For the FACT/GOG-NTX neuropathy, each item is scored from 0-4, and the neurotoxicity total score is the sum of the scores for the 11 items, and ranges from 0 to 44. Lower values of the FACT/GOG-NTX neurotoxicity total score indicate higher neurotoxicity. The FACT/GOG-NTX neurotoxicity total score will be analyzed as a continuous variable. Proper transformation to improve normality will be used if needed. Change in FACT/GOG-NTX neuropathy score will be defined as the difference in score values between baseline versus after 12 weeks of taxane chemotherapy.

  From baseline to after completion of 12 weeks of taxane chemotherapy

Secondary Outcomes (8)

• Rate of grade 2-4 TIPN assessed by treating physician

  After completion of 12 weeks of taxane chemotherapy and at 24 weeks and 12 months after completing taxane chemotherapy

• Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) survey score

  After completion of 12 weeks of taxane chemotherapy

• Change in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) quality of life survey score

  From baseline to the completion of 12 weeks of taxane chemotherapy

• Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 29 v2.1 survey score

  From baseline to the completion of 12 weeks of taxane chemotherapy

• European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) - Chemotherapy-induced Peripheral Neuropathy twenty-item scale (CIPN20) (EORTC QLQ CIPN20) survey score

  12 weeks after the completion of taxane chemotherapy

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Paclitaxel or Docetaxel for 12 weeks and Placebo

Drug: Placebo

Desloratodine

EXPERIMENTAL

Paclitaxel or Docetaxel for 12 weeks and Desloratadine

Drug: Desloratodine

Interventions

Desloratodine DRUG

Desloratadine 5mg PO every other day for 12 weeks. Desloratadine is a long- acting tricyclic histamine antagonist with selective H1-receptor histamine antagonist activity. Desloratadine inhibited histamine release from human mast cells.

Desloratodine

Placebo DRUG

Placebo daily PO for 12 weeks. Placebo is a lactose filler covered by a capsule.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed breast cancer, stage I-III as per the American Joint Committee on Cancer (AJCC) 8th edition (Anatomic Staging)
• Patients must be planned to receive taxane-based regimen for breast cancer (Adjuvant or neoadjuvant) of at least 12 weeks duration. Patients planned to receive taxanes in combination with other chemotherapy drugs (including platinums) are eligible. Patients planned to receive taxanes plus single or dual antiher2 therapy are also eligible. Patients planned to receive taxane-based regimen with immune checkpoint inhibitors are also allowed
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%)
• Patients must have an adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/microliter (mcL)
• platelets ≥100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
• Creatinine ≤ institutional ULN
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with prior diagnosis of diabetes mellitus are allowed if the patient has no peripheral neuropathy
• Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
• Patients must not have received prior taxane or platinum therapy
• Women of childbearing potential must have a negative pregnancy test: serum or urine beta human chorionic gonadotropin (hCG) within 14 days prior to first dose of study treatment

You may not qualify if:

• Patients with prior diagnosis of peripheral neuropathy
• Patients who received chemotherapy for the current breast cancer diagnosis before the planned taxane-based regimen
• Patients who are receiving any other investigation agents
• Patients with concurrent use of antihistamines during or for 2 days prior to the study period
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to desloratadine
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
• Pregnant or breastfeeding women are not allowed in the study
• Patients who are taking probiotics
• Patients who are using chronic laxatives or enema
• Patients who used antibiotics within 4 weeks of registration

Sponsors & Collaborators

• Montefiore Medical Center: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Related Publications (83)

• Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17.

  PMID: 38230766 BACKGROUND

• Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL Group. Psychol Med. 1998 May;28(3):551-8. doi: 10.1017/s0033291798006667.

  PMID: 9626712 BACKGROUND

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Electronic address: bc.overview@ctsu.ox.ac.uk; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials. Lancet. 2023 Apr 15;401(10384):1277-1292. doi: 10.1016/S0140-6736(23)00285-4.

  PMID: 37061269 BACKGROUND

• Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc. 1971 May 5;93(9):2325-7. doi: 10.1021/ja00738a045. No abstract available.

  PMID: 5553076 BACKGROUND

• Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature. 1979 Feb 22;277(5698):665-7. doi: 10.1038/277665a0. No abstract available.

  PMID: 423966 BACKGROUND

• Horwitz SB. Personal recollections on the early development of taxol. J Nat Prod. 2004 Feb;67(2):136-8. doi: 10.1021/np0304464.

  PMID: 14987047 BACKGROUND

• Zasadil LM, Andersen KA, Yeum D, Rocque GB, Wilke LG, Tevaarwerk AJ, Raines RT, Burkard ME, Weaver BA. Cytotoxicity of paclitaxel in breast cancer is due to chromosome missegregation on multipolar spindles. Sci Transl Med. 2014 Mar 26;6(229):229ra43. doi: 10.1126/scitranslmed.3007965.

  PMID: 24670687 BACKGROUND

• Weaver BA. How Taxol/paclitaxel kills cancer cells. Mol Biol Cell. 2014 Sep 15;25(18):2677-81. doi: 10.1091/mbc.E14-04-0916.

  PMID: 25213191 BACKGROUND

• Cortes JE, Pazdur R. Docetaxel. J Clin Oncol. 1995 Oct;13(10):2643-55. doi: 10.1200/JCO.1995.13.10.2643.

  PMID: 7595719 BACKGROUND

• Gradishar WJ. Albumin-bound paclitaxel: a next-generation taxane. Expert Opin Pharmacother. 2006 Jun;7(8):1041-53. doi: 10.1517/14656566.7.8.1041.

  PMID: 16722814 BACKGROUND

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012 Feb 4;379(9814):432-44. doi: 10.1016/S0140-6736(11)61625-5. Epub 2011 Dec 5.

  PMID: 22152853 BACKGROUND

• Rowinsky EK, Donehower RC. Paclitaxel (taxol). N Engl J Med. 1995 Apr 13;332(15):1004-14. doi: 10.1056/NEJM199504133321507. No abstract available.

  PMID: 7885406 BACKGROUND

• Ringel I, Horwitz SB. Studies with RP 56976 (taxotere): a semisynthetic analogue of taxol. J Natl Cancer Inst. 1991 Feb 20;83(4):288-91. doi: 10.1093/jnci/83.4.288.

  PMID: 1671606 BACKGROUND

• Schneider BP, Shen F, Jiang G, O'Neill A, Radovich M, Li L, Gardner L, Lai D, Foroud T, Sparano JA, Sledge GW Jr, Miller KD. Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-E5103. JCO Precis Oncol. 2017;2017:PO.17.00059. doi: 10.1200/PO.17.00059. Epub 2017 Aug 21.

  PMID: 29333527 BACKGROUND

• Michalova Z, Szekiova E, Blasko J, Vanicky I. Prevention and therapy of chemotherapy-induced peripheral neuropathy: a review of recent findings. Neoplasma. 2023 Feb;70(1):15-35. doi: 10.4149/neo_2022_221007N992. Epub 2022 Dec 28.

  PMID: 36573482 BACKGROUND

• Sahenk Z, Barohn R, New P, Mendell JR. Taxol neuropathy. Electrodiagnostic and sural nerve biopsy findings. Arch Neurol. 1994 Jul;51(7):726-9. doi: 10.1001/archneur.1994.00540190110024.

  PMID: 7912506 BACKGROUND

• Komiya Y, Tashiro T. Effects of taxol on slow and fast axonal transport. Cell Motil Cytoskeleton. 1988;11(3):151-6. doi: 10.1002/cm.970110302.

  PMID: 2463106 BACKGROUND

• Han Y, Smith MT. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN). Front Pharmacol. 2013 Dec 18;4:156. doi: 10.3389/fphar.2013.00156.

  PMID: 24385965 BACKGROUND

• Guo C, Sun L, Chen X, Zhang D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res. 2013 Jul 25;8(21):2003-14. doi: 10.3969/j.issn.1673-5374.2013.21.009.

  PMID: 25206509 BACKGROUND

• Zhang H, Boyette-Davis JA, Kosturakis AK, Li Y, Yoon SY, Walters ET, Dougherty PM. Induction of monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 in primary sensory neurons contributes to paclitaxel-induced peripheral neuropathy. J Pain. 2013 Oct;14(10):1031-44. doi: 10.1016/j.jpain.2013.03.012. Epub 2013 May 31.

  PMID: 23726937 BACKGROUND

• Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner GJ, Ji RR, Bean BP, Woolf CJ, Samad TA. Nociceptors are interleukin-1beta sensors. J Neurosci. 2008 Dec 24;28(52):14062-73. doi: 10.1523/JNEUROSCI.3795-08.2008.

  PMID: 19109489 BACKGROUND

• Sorkin LS, Xiao WH, Wagner R, Myers RR. Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience. 1997 Nov;81(1):255-62. doi: 10.1016/s0306-4522(97)00147-4.

  PMID: 9300418 BACKGROUND

• Ozaktay AC, Cavanaugh JM, Asik I, DeLeo JA, Weinstein JN. Dorsal root sensitivity to interleukin-1 beta, interleukin-6 and tumor necrosis factor in rats. Eur Spine J. 2002 Oct;11(5):467-75. doi: 10.1007/s00586-002-0430-x. Epub 2002 Jun 4.

  PMID: 12384756 BACKGROUND

• McMahon SB, Cafferty WB, Marchand F. Immune and glial cell factors as pain mediators and modulators. Exp Neurol. 2005 Apr;192(2):444-62. doi: 10.1016/j.expneurol.2004.11.001.

  PMID: 15755561 BACKGROUND

• Loprinzi CL, Lacchetti C, Bleeker J, Cavaletti G, Chauhan C, Hertz DL, Kelley MR, Lavino A, Lustberg MB, Paice JA, Schneider BP, Lavoie Smith EM, Smith ML, Smith TJ, Wagner-Johnston N, Hershman DL. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol. 2020 Oct 1;38(28):3325-3348. doi: 10.1200/JCO.20.01399. Epub 2020 Jul 14.

  PMID: 32663120 BACKGROUND

• Huang HQ, Brady MF, Cella D, Fleming G. Validation and reduction of FACT/GOG-Ntx subscale for platinum/paclitaxel-induced neurologic symptoms: a gynecologic oncology group study. Int J Gynecol Cancer. 2007 Mar-Apr;17(2):387-93. doi: 10.1111/j.1525-1438.2007.00794.x.

  PMID: 17362317 BACKGROUND

• Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, Amtmann D, Bode R, Buysse D, Choi S, Cook K, Devellis R, DeWalt D, Fries JF, Gershon R, Hahn EA, Lai JS, Pilkonis P, Revicki D, Rose M, Weinfurt K, Hays R; PROMIS Cooperative Group. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol. 2010 Nov;63(11):1179-94. doi: 10.1016/j.jclinepi.2010.04.011. Epub 2010 Aug 4.

  PMID: 20685078 BACKGROUND

• Cheng HL, Lopez V, Lam SC, Leung AKT, Li YC, Wong KH, Au JSK, Sundar R, Chan A, De Ng TR, Suen LKP, Chan CW, Yorke J, Molassiotis A. Psychometric testing of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy. Health Qual Life Outcomes. 2020 Jul 23;18(1):246. doi: 10.1186/s12955-020-01493-y.

  PMID: 32703223 BACKGROUND

• Beijers AJM, Bonhof CS, Mols F, Ophorst J, de Vos-Geelen J, Jacobs EMG, van de Poll-Franse LV, Vreugdenhil G. Multicenter randomized controlled trial to evaluate the efficacy and tolerability of frozen gloves for the prevention of chemotherapy-induced peripheral neuropathy. Ann Oncol. 2020 Jan;31(1):131-136. doi: 10.1016/j.annonc.2019.09.006.

  PMID: 31912787 BACKGROUND

• Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003 May;41(5):582-92. doi: 10.1097/01.MLR.0000062554.74615.4C.

  PMID: 12719681 BACKGROUND

• Tsuyuki S, Yamagami K, Yoshibayashi H, Sugie T, Mizuno Y, Tanaka S, Kato H, Okuno T, Ogura N, Yamashiro H, Takuwa H, Kikawa Y, Hashimoto T, Kato T, Takahara S, Katayama T, Yamauchi A, Inamoto T. Effectiveness and safety of surgical glove compression therapy as a prophylactic method against nanoparticle albumin-bound-paclitaxel-induced peripheral neuropathy. Breast. 2019 Oct;47:22-27. doi: 10.1016/j.breast.2019.06.008. Epub 2019 Jul 3.

  PMID: 31302389 BACKGROUND

• Su Y, Huang J, Wang S, Unger JM, Arias-Fuenzalida J, Shi Y, Li J, Gao Y, Shi W, Wang X, Peng R, Xu F, An X, Xue C, Xia W, Hong R, Zhong Y, Lin Y, Huang H, Zhang A, Zhang L, Cai L, Zhang J, Yuan Z. The Effects of Ganglioside-Monosialic Acid in Taxane-Induced Peripheral Neurotoxicity in Patients with Breast Cancer: A Randomized Trial. J Natl Cancer Inst. 2020 Jan 1;112(1):55-62. doi: 10.1093/jnci/djz086.

  PMID: 31093677 BACKGROUND

• Murdoch D, Goa KL, Keam SJ. Desloratadine: an update of its efficacy in the management of allergic disorders. Drugs. 2003;63(19):2051-77. doi: 10.2165/00003495-200363190-00010.

  PMID: 12962522 BACKGROUND

• Anampa J, Makower D, Sparano JA. Progress in adjuvant chemotherapy for breast cancer: an overview. BMC Med. 2015 Aug 17;13:195. doi: 10.1186/s12916-015-0439-8.

  PMID: 26278220 BACKGROUND

• Liu X, Tonello R, Ling Y, Gao YJ, Berta T. Paclitaxel-activated astrocytes produce mechanical allodynia in mice by releasing tumor necrosis factor-alpha and stromal-derived cell factor 1. J Neuroinflammation. 2019 Nov 10;16(1):209. doi: 10.1186/s12974-019-1619-9.

  PMID: 31707979 BACKGROUND

• Brandolini L, d'Angelo M, Novelli R, Castelli V, Giorgio C, Sirico A, Cocchiaro P, D'Egidio F, Benedetti E, Cristiano C, Bugatti A, Ruocco A, Amendola PG, Talarico C, Manelfi C, Iaconis D, Beccari A, Quadros AU, Cunha TM, Caruso A, Russo R, Cimini A, Aramini A, Allegretti M. Paclitaxel binds and activates C5aR1: A new potential therapeutic target for the prevention of chemotherapy-induced peripheral neuropathy and hypersensitivity reactions. Cell Death Dis. 2022 May 25;13(5):500. doi: 10.1038/s41419-022-04964-w.

  PMID: 35614037 BACKGROUND

• Escribese MM, Rosace D, Chivato T, Fernandez TD, Corbi AL, Barber D. Alternative Anaphylactic Routes: The Potential Role of Macrophages. Front Immunol. 2017 May 8;8:515. doi: 10.3389/fimmu.2017.00515. eCollection 2017.

  PMID: 28533777 BACKGROUND

• Wang J, Zhou Y, Zhang H, Hu L, Liu J, Wang L, Wang T, Zhang H, Cong L, Wang Q. Pathogenesis of allergic diseases and implications for therapeutic interventions. Signal Transduct Target Ther. 2023 Mar 24;8(1):138. doi: 10.1038/s41392-023-01344-4.

  PMID: 36964157 BACKGROUND

• Yu J, Lou GD, Yue JX, Tang YY, Hou WW, Shou WT, Ohtsu H, Zhang SH, Chen Z. Effects of histamine on spontaneous neuropathic pain induced by peripheral axotomy. Neurosci Bull. 2013 Jun;29(3):261-9. doi: 10.1007/s12264-013-1316-0. Epub 2013 Mar 13.

  PMID: 23494529 BACKGROUND

• Hunto ST, Kim HG, Baek KS, Jeong D, Kim E, Kim JH, Cho JY. Loratadine, an antihistamine drug, exhibits anti-inflammatory activity through suppression of the NF-kB pathway. Biochem Pharmacol. 2020 Jul;177:113949. doi: 10.1016/j.bcp.2020.113949. Epub 2020 Apr 3.

  PMID: 32251678 BACKGROUND

• Jang J, Hunto ST, Kim JW, Lee HP, Kim HG, Cho JY. Anti-Inflammatory Activities of an Anti-Histamine Drug, Loratadine, by Suppressing TAK1 in AP-1 Pathway. Int J Mol Sci. 2022 Apr 3;23(7):3986. doi: 10.3390/ijms23073986.

  PMID: 35409346 BACKGROUND

• Kamal N, Abdallah MS, Abdel Wahed E, Sabri NA, Fahmy SF. Evaluation of the Effect of Loratadine versus Diosmin/Hesperidin Combination on Vinca Alkaloids-Induced Neuropathy: A Randomized Controlled Clinical Trial. Pharmaceuticals (Basel). 2024 May 9;17(5):609. doi: 10.3390/ph17050609.

  PMID: 38794179 BACKGROUND

• Canonica GW, Blaiss M. Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence. World Allergy Organ J. 2011 Feb;4(2):47-53. doi: 10.1097/WOX.0b013e3182093e19. Epub 2011 Feb 23.

  PMID: 23268457 BACKGROUND

• Wu RL, Anthes JC, Kreutner W, Harris AG, West RE Jr. Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-kappaB activity consistent with inverse agonism at the histamine H1 Receptor. Int Arch Allergy Immunol. 2004 Dec;135(4):313-8. doi: 10.1159/000082325. Epub 2004 Nov 24.

  PMID: 15564772 BACKGROUND

• Lu J, Zhao XJ, Ruan Y, Liu XJ, Di X, Xu R, Wang JY, Qian MY, Jin HM, Li WJ, Shen X. Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice. Acta Pharmacol Sin. 2024 Oct;45(10):2061-2076. doi: 10.1038/s41401-024-01301-z. Epub 2024 May 24.

  PMID: 38789495 BACKGROUND

• Ma J, Kavelaars A, Dougherty PM, Heijnen CJ. Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source. Cancer. 2018 Jun 1;124(11):2289-2298. doi: 10.1002/cncr.31248. Epub 2018 Feb 20.

  PMID: 29461625 BACKGROUND

• Boyette-Davis JA, Cata JP, Driver LC, Novy DM, Bruel BM, Mooring DL, Wendelschafer-Crabb G, Kennedy WR, Dougherty PM. Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine. Cancer Chemother Pharmacol. 2013 Mar;71(3):619-26. doi: 10.1007/s00280-012-2047-z. Epub 2012 Dec 11.

  PMID: 23228992 BACKGROUND

• Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med. 2012 Nov 29;10:239. doi: 10.1186/1479-5876-10-239.

  PMID: 23190582 BACKGROUND

• Cavaletti G, Bogliun G, Marzorati L, Zincone A, Piatti M, Colombo N, Franchi D, La Presa MT, Lissoni A, Buda A, Fei F, Cundari S, Zanna C. Early predictors of peripheral neurotoxicity in cisplatin and paclitaxel combination chemotherapy. Ann Oncol. 2004 Sep;15(9):1439-42. doi: 10.1093/annonc/mdh348.

  PMID: 15319252 BACKGROUND

• Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of Chemotherapy-Induced Peripheral Neuropathy: Current Status and Future Directions. Front Pain Res (Lausanne). 2022 Mar 14;3:864910. doi: 10.3389/fpain.2022.864910. eCollection 2022.

  PMID: 35360655 BACKGROUND

• Karteri S, Bruna J, Argyriou AA, Mariotto S, Velasco R, Alemany M, Kalofonou F, Alberti P, Dinoto A, Velissaris D, Stradella A, Cavaletti G, Ferrari S, Kalofonos HP. Prospectively assessing serum neurofilament light chain levels as a biomarker of paclitaxel-induced peripheral neurotoxicity in breast cancer patients. J Peripher Nerv Syst. 2022 Jun;27(2):166-174. doi: 10.1111/jns.12493. Epub 2022 Apr 13.

  PMID: 35384143 BACKGROUND

• Youk J, Kim YS, Lim JA, Shin DY, Koh Y, Lee ST, Kim I. Depletion of nerve growth factor in chemotherapy-induced peripheral neuropathy associated with hematologic malignancies. PLoS One. 2017 Aug 21;12(8):e0183491. doi: 10.1371/journal.pone.0183491. eCollection 2017.

  PMID: 28827818 BACKGROUND

• Shatunova S, Aktar R, Peiris M, Lee JYP, Vetter I, Starobova H. The role of the gut microbiome in neuroinflammation and chemotherapy-induced peripheral neuropathy. Eur J Pharmacol. 2024 Sep 15;979:176818. doi: 10.1016/j.ejphar.2024.176818. Epub 2024 Jul 18.

  PMID: 39029779 BACKGROUND

• Singh SK, Krukowski K, Laumet GO, Weis D, Alexander JF, Heijnen CJ, Kavelaars A. CD8+ T cell-derived IL-13 increases macrophage IL-10 to resolve neuropathic pain. JCI Insight. 2022 Mar 8;7(5):e154194. doi: 10.1172/jci.insight.154194.

  PMID: 35260535 BACKGROUND

• Uceyler N, Rogausch JP, Toyka KV, Sommer C. Differential expression of cytokines in painful and painless neuropathies. Neurology. 2007 Jul 3;69(1):42-9. doi: 10.1212/01.wnl.0000265062.92340.a5.

  PMID: 17606879 BACKGROUND

• Kleckner IR, Jusko TA, Culakova E, Chung K, Kleckner AS, Asare M, Inglis JE, Loh KP, Peppone LJ, Miller J, Melnik M, Kasbari S, Ossip D, Mustian KM. Longitudinal study of inflammatory, behavioral, clinical, and psychosocial risk factors for chemotherapy-induced peripheral neuropathy. Breast Cancer Res Treat. 2021 Sep;189(2):521-532. doi: 10.1007/s10549-021-06304-6. Epub 2021 Jun 30.

  PMID: 34191201 BACKGROUND

• Rumore MM, Schlichting DA. Clinical efficacy of antihistaminics as analgesics. Pain. 1986 Apr;25(1):7-22. doi: 10.1016/0304-3959(86)90004-7.

  PMID: 2872645 BACKGROUND

• Al-Mazidi S, Alotaibi M, Nedjadi T, Chaudhary A, Alzoghaibi M, Djouhri L. Blocking of cytokines signalling attenuates evoked and spontaneous neuropathic pain behaviours in the paclitaxel rat model of chemotherapy-induced neuropathy. Eur J Pain. 2018 Apr;22(4):810-821. doi: 10.1002/ejp.1169. Epub 2017 Dec 27.

  PMID: 29282807 BACKGROUND

• Manjavachi MN, Passos GF, Trevisan G, Araujo SB, Pontes JP, Fernandes ES, Costa R, Calixto JB. Spinal blockage of CXCL1 and its receptor CXCR2 inhibits paclitaxel-induced peripheral neuropathy in mice. Neuropharmacology. 2019 Jun;151:136-143. doi: 10.1016/j.neuropharm.2019.04.014. Epub 2019 Apr 13.

  PMID: 30991054 BACKGROUND

• Nakamura T, Kawarabayashi T, Shibata M, Kasahara H, Makioka K, Sugawara T, Oka H, Ishizawa K, Amari M, Ueda T, Kinoshita S, Miyamoto Y, Kaito K, Takatama M, Ikeda Y, Shoji M. High levels of plasma neurofilament light chain correlated with brainstem and peripheral nerve damage. J Neurol Sci. 2024 Aug 15;463:123137. doi: 10.1016/j.jns.2024.123137. Epub 2024 Jul 15.

  PMID: 39032446 BACKGROUND

• Velasco R, Marco C, Domingo-Domenech E, Stradella A, Santos C, Laquente B, Ferrer G, Argyriou AA, Bruna J. Plasma neurofilament light chain levels in chemotherapy-induced peripheral neurotoxicity according to type of anticancer drug. Eur J Neurol. 2024 Sep;31(9):e16369. doi: 10.1111/ene.16369. Epub 2024 Jul 1.

  PMID: 38952074 BACKGROUND

• Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Mantovani A, Weyand CM, Barzilai N, Goronzy JJ, Rando TA, Effros RB, Lucia A, Kleinstreuer N, Slavich GM. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019 Dec;25(12):1822-1832. doi: 10.1038/s41591-019-0675-0. Epub 2019 Dec 5.

  PMID: 31806905 BACKGROUND

• Muller DN, Wilck N, Haase S, Kleinewietfeld M, Linker RA. Sodium in the microenvironment regulates immune responses and tissue homeostasis. Nat Rev Immunol. 2019 Apr;19(4):243-254. doi: 10.1038/s41577-018-0113-4.

  PMID: 30644452 BACKGROUND

• Chassaing B, Van de Wiele T, De Bodt J, Marzorati M, Gewirtz AT. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut. 2017 Aug;66(8):1414-1427. doi: 10.1136/gutjnl-2016-313099. Epub 2017 Mar 21.

  PMID: 28325746 BACKGROUND

• Meneses-Echavez JF, Correa-Bautista JE, Gonzalez-Jimenez E, Schmidt Rio-Valle J, Elkins MR, Lobelo F, Ramirez-Velez R. The Effect of Exercise Training on Mediators of Inflammation in Breast Cancer Survivors: A Systematic Review with Meta-analysis. Cancer Epidemiol Biomarkers Prev. 2016 Jul;25(7):1009-17. doi: 10.1158/1055-9965.EPI-15-1061. Epub 2016 Apr 12.

  PMID: 27197276 BACKGROUND

• Khanna D, Khanna S, Khanna P, Kahar P, Patel BM. Obesity: A Chronic Low-Grade Inflammation and Its Markers. Cureus. 2022 Feb 28;14(2):e22711. doi: 10.7759/cureus.22711. eCollection 2022 Feb.

  PMID: 35386146 BACKGROUND

• Reutrakul S, Van Cauter E. Sleep influences on obesity, insulin resistance, and risk of type 2 diabetes. Metabolism. 2018 Jul;84:56-66. doi: 10.1016/j.metabol.2018.02.010. Epub 2018 Mar 3.

  PMID: 29510179 BACKGROUND

• Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS, Turner RB. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):5995-9. doi: 10.1073/pnas.1118355109. Epub 2012 Apr 2.

  PMID: 22474371 BACKGROUND

• Ghoreishi Z, Keshavarz S, Asghari Jafarabadi M, Fathifar Z, Goodman KA, Esfahani A. Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer. BMC Cancer. 2018 Oct 5;18(1):958. doi: 10.1186/s12885-018-4869-5.

  PMID: 30290775 BACKGROUND

• Greenlee H, Hershman DL, Shi Z, Kwan ML, Ergas IJ, Roh JM, Kushi LH. BMI, Lifestyle Factors and Taxane-Induced Neuropathy in Breast Cancer Patients: The Pathways Study. J Natl Cancer Inst. 2016 Oct 28;109(2):djw206. doi: 10.1093/jnci/djw206. Print 2017 Feb.

  PMID: 27794123 BACKGROUND

• Zhang F, Aschenbrenner D, Yoo JY, Zuo T. The gut mycobiome in health, disease, and clinical applications in association with the gut bacterial microbiome assembly. Lancet Microbe. 2022 Dec;3(12):e969-e983. doi: 10.1016/S2666-5247(22)00203-8. Epub 2022 Sep 28.

  PMID: 36182668 BACKGROUND

• Otto-Dobos LD, Grant CV, Lahoud AA, Wilcox OR, Strehle LD, Loman BR, Adarkwah Yiadom S, Seng MM, Halloy NR, Russart KLG, Carpenter KM, Dawson E, Sardesai SD, Williams NO, Gatti-Mays ME, Stover DG, Sudheendra PK, Wesolowski R, Kiecolt-Glaser JK, Bailey MT, Andridge RR, Pyter LM. Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer. Brain Behav Immun. 2024 Aug;120:208-220. doi: 10.1016/j.bbi.2024.05.039. Epub 2024 May 31.

  PMID: 38823430 BACKGROUND

• Ramakrishna C, Corleto J, Ruegger PM, Logan GD, Peacock BB, Mendonca S, Yamaki S, Adamson T, Ermel R, McKemy D, Borneman J, Cantin EM. Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain. Sci Rep. 2019 Dec 30;9(1):20324. doi: 10.1038/s41598-019-56832-x.

  PMID: 31889131 BACKGROUND

• Cuozzo M, Castelli V, Avagliano C, Cimini A, d'Angelo M, Cristiano C, Russo R. Effects of Chronic Oral Probiotic Treatment in Paclitaxel-Induced Neuropathic Pain. Biomedicines. 2021 Mar 30;9(4):346. doi: 10.3390/biomedicines9040346.

  PMID: 33808052 BACKGROUND

• Shen S, Lim G, You Z, Ding W, Huang P, Ran C, Doheny J, Caravan P, Tate S, Hu K, Kim H, McCabe M, Huang B, Xie Z, Kwon D, Chen L, Mao J. Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci. 2017 Sep;20(9):1213-1216. doi: 10.1038/nn.4606. Epub 2017 Jul 17.

  PMID: 28714953 BACKGROUND

• Terrisse S, Derosa L, Iebba V, Ghiringhelli F, Vaz-Luis I, Kroemer G, Fidelle M, Christodoulidis S, Segata N, Thomas AM, Martin AL, Sirven A, Everhard S, Aprahamian F, Nirmalathasan N, Aarnoutse R, Smidt M, Ziemons J, Caldas C, Loibl S, Denkert C, Durand S, Iglesias C, Pietrantonio F, Routy B, Andre F, Pasolli E, Delaloge S, Zitvogel L. Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment. Cell Death Differ. 2021 Sep;28(9):2778-2796. doi: 10.1038/s41418-021-00784-1. Epub 2021 May 7.

  PMID: 33963313 BACKGROUND

• Lavoie Smith EM, Barton DL, Qin R, Steen PD, Aaronson NK, Loprinzi CL. Assessing patient-reported peripheral neuropathy: the reliability and validity of the European Organization for Research and Treatment of Cancer QLQ-CIPN20 Questionnaire. Qual Life Res. 2013 Dec;22(10):2787-99. doi: 10.1007/s11136-013-0379-8. Epub 2013 Mar 30.

  PMID: 23543373 BACKGROUND

• Le-Rademacher J, Kanwar R, Seisler D, Pachman DR, Qin R, Abyzov A, Ruddy KJ, Banck MS, Lavoie Smith EM, Dorsey SG, Aaronson NK, Sloan J, Loprinzi CL, Beutler AS. Patient-reported (EORTC QLQ-CIPN20) versus physician-reported (CTCAE) quantification of oxaliplatin- and paclitaxel/carboplatin-induced peripheral neuropathy in NCCTG/Alliance clinical trials. Support Care Cancer. 2017 Nov;25(11):3537-3544. doi: 10.1007/s00520-017-3780-y. Epub 2017 Jun 20.

  PMID: 28634656 BACKGROUND

• Calhoun EA, Welshman EE, Chang CH, Lurain JR, Fishman DA, Hunt TL, Cella D. Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer. 2003 Nov-Dec;13(6):741-8. doi: 10.1111/j.1525-1438.2003.13603.x.

  PMID: 14675309 BACKGROUND

• Cella D, Peterman A, Hudgens S, Webster K, Socinski MA. Measuring the side effects of taxane therapy in oncology: the functional assesment of cancer therapy-taxane (FACT-taxane). Cancer. 2003 Aug 15;98(4):822-31. doi: 10.1002/cncr.11578.

  PMID: 12910528 BACKGROUND

• Hershman DL, Unger JM, Crew KD, Minasian LM, Awad D, Moinpour CM, Hansen L, Lew DL, Greenlee H, Fehrenbacher L, Wade JL 3rd, Wong SF, Hortobagyi GN, Meyskens FL, Albain KS. Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. J Clin Oncol. 2013 Jul 10;31(20):2627-33. doi: 10.1200/JCO.2012.44.8738. Epub 2013 Jun 3.

  PMID: 23733756 BACKGROUND

• Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB, Winicour P, Brannon J. The Functional Assessment of Cancer Therapy Scale: Development and Validation of the General Measure. J Clin Oncol. 2023 Dec 10;41(35):5335-5344. doi: 10.1200/JCO.22.02775.

  PMID: 38056080 BACKGROUND

• Park SB, Goldstein D, Krishnan AV, Lin CS, Friedlander ML, Cassidy J, Koltzenburg M, Kiernan MC. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin. 2013 Nov-Dec;63(6):419-37. doi: 10.3322/caac.21204.

  PMID: 24590861 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Peripheral Nervous System Diseases

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Jesus R Anampa, MD, MS

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jesus R Anampa, MD, MS

CONTACT

7184058505; janampa@montefiore.org

Rikin Ghandi

CONTACT

9149531890; rikin.gandhi@einsteinmed.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Permuted block randomization procedure will be used for which patients will be randomized between the two treatment arms and stratified using the following criteria specified: * Taxane drug: Paclitaxel vs. docetaxel * Platinum use: Yes vs. No

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: August 7, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)