"The Effect of Memantine on the Prevention and Amelioration of Paclitaxel-induced Toxicity in Breast Cancer Patients"

NCT06679387 | Recruiting Phase 2

• 1 other identifier: 45
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Cancer is currently a leading cause of morbidity and mortality worldwide. Chemotherapeutic agents, despite being effective in arresting the progression of cancer by targeting and eliminating rapidly dividing cancer cells, are associated with various adverse effects. Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical adverse effect of certain chemotherapeutic agents. For many patients, CIPN symptoms could be severe, disabling, and significantly impairing the activities of daily living (ADL) and diminishing the quality of life (QoL). Paclitaxel-induced peripheral neuropathy may affect up to 97% of paclitaxel-treated patients and become chronic in more than 60% of cases. The initial symptoms of paclitaxel-induced peripheral neuropathy (PIPN) include numbness, tingling, and allodynia (painful sensations in response to normally non-painful stimuli) that can be manifested in the patient's fingers and toes within 24-72 h post-injection. These symptoms may later progress to affect the patient's lower leg and wrists in a "glove and stocking" pattern. Symptoms typically begin distally and continue proximally as the situation worsens. Memantine is a non-competitive NMDA receptor antagonist that inhibits the prolonged influx of Ca2+, responsible for neuronal excitotoxicity while maintaining the physiological NMDA receptor's function and avoiding psychotropic adverse events. Although memantine has been the main treatment option for moderate and severe Alzheimer's disease in the last two decades, numerous studies have investigated its other potential uses. Some studies showed that memantine diminished chronic pain in complex regional pain syndrome, phantom limb pain, and fibromyalgia. Most in vivo and in vitro studies attributed the neuroprotective effects of memantine to the blockade of NMDA receptors on neurons as well as inhibition of microglia activation with subsequent reduction of pro-inflammatory mediators' production such as extracellular superoxide anion, intracellular ROS, nitric oxide, prostaglandin E2, and TNF-α, and stimulation of neurotrophic factor release from astroglia.

Conditions

Breast Cancer Early Stage Breast Cancer (Stage 1-3)

Keywords

Paclitaxel-induced Toxicity; Breast Cancer patients; Memantine; Neurotoxicity Prevention or treatment

Outcome Measures

Primary Outcomes (1)

• Incidence and grading of paclitaxel induced peripheral neuropathy (PIPN)

  Patients will be subjected to neurological examination every cycle to identify the presence and severity of PIPN. Grading of PIPN will be determined using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5 published in November 2017 (NCI, 2017). The NCI-CTCAE grades the adverse events based on their severity on a 5-point scale where "Grade 1" is defined as: Mild or asymptomatic symptoms requiring clinical or diagnostic observations only; Intervention not indicated. "Grade 2": Moderate symptoms limiting age-appropriate ADL; minimal, local or noninvasive intervention is indicated. "Grade 3": Severe symptoms or medically significant but not life-threatening that are disabling or limiting self-care in ADL; hospitalization or prolongation of hospitalization is indicated. "Grade 4": Life threatening consequences; urgent or emergent intervention is needed. "Grade 5": Death related to adverse event. The primary outcome will be the difference i

  Weekly for 12 weeks.

Secondary Outcomes (4)

• Pain severity

  Weekly for 12 weeks.

• Patients' QoL

  baseline, at 6 weeks, and 12 weeks.

• Serum levels of nerve growth factor (NGF)

  Baseline and at 12 weeks.

• Severity of depressive symptoms

  Baseline, at 6 weeks, and 12 weeks.

Study Arms (2)

Treatment arm

EXPERIMENTAL

Forty patients who will receive memantine 20 mg once daily in addition to weekly 80 mg/m2 of paclitaxel for 12 weeks.

Drug: Memantine-HCl

Control arm

PLACEBO COMPARATOR

Forty patients who will receive placebo once daily in addition to weekly 80 mg/m2 of paclitaxel for 12 weeks.

Drug: Placebo Oral Tablet

Interventions

Memantine-HCl DRUG

Memantine hydrochloride 20 mg once daily for 12 weeks.

Also known as: Memantine 20 mg

Treatment arm

Placebo Oral Tablet DRUG

A once daily matched tablet of placebo for 12 weeks

Also known as: Placebo comparator

Control arm

Eligibility Criteria

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

You may qualify if:

• Adult patients (\>18 years old).
• Patients with confirmed diagnosis of non-metastatic breast cancer planned to receive weekly adjuvant/neo-adjuvant paclitaxel.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance (Oken et al., 1982) status of 0-2.

You may not qualify if:

• Patients with pre-existing neuropathic conditions.
• Patients with diabetes mellitus.
• Patients with a history of seizure disorder.
• Patients with renal impairment (creatinine clearance less than 60 ml/min), or hepatic impairment (defined as ALT an AST \> 3 times upper limits of normal)
• Patients with inadequate bone marrow functions (defined as absolute neutrophilic count less than 1,500/mm3 or platelets count less than 100,000/mm3).
• Concomitant use of vitamin B1, B6, B9, or B12.
• Patients receiving medications that possibly induce peripheral neuropathy including amiodarone, colchicine, metronidazole, antimycobacterials, and nucleoside reverse transcriptase inhibitors, and phenytoin (Jones et al., 2020).
• Patients receiving gabapentinoids, antidepressants, or opioids.
• Pregnancy or lactation.
• History of hypersensitivity to memantine.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ain shams University Hospitals

Cairo, Egypt

RECRUITING

Related Publications (2)

• Folch J, Busquets O, Ettcheto M, Sanchez-Lopez E, Castro-Torres RD, Verdaguer E, Garcia ML, Olloquequi J, Casadesus G, Beas-Zarate C, Pelegri C, Vilaplana J, Auladell C, Camins A. Memantine for the Treatment of Dementia: A Review on its Current and Future Applications. J Alzheimers Dis. 2018;62(3):1223-1240. doi: 10.3233/JAD-170672.

  PMID: 29254093 BACKGROUND

• Argyriou AA, Koltzenburg M, Polychronopoulos P, Papapetropoulos S, Kalofonos HP. Peripheral nerve damage associated with administration of taxanes in patients with cancer. Crit Rev Oncol Hematol. 2008 Jun;66(3):218-28. doi: 10.1016/j.critrevonc.2008.01.008. Epub 2008 Mar 7.

  PMID: 18329278 BACKGROUND

MeSH Terms

Interventions

Memantine

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Mahmoud M Gharib, Assistant lecturer

CONTACT

02 01286584470; dr.mahmoudgharib.mg@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer at Pharmacy Practice & Clinical Pharmacy Department, Future University in Egypt

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 7, 2024
• Study Start: October 30, 2024
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: November 7, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)