Breast Cancer Early Stage Breast Cancer (Stage 1-3)Phase 2NCT06679387
"The Effect of Memantine on the Prevention and Amelioration of Paclitaxel-induced Toxicity in Breast Cancer Patients"
A Phase 2 study testing Memantine-HCl in people with Breast Cancer Early Stage Breast Cancer (Stage 1-3), run by Ain Shams University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer Early Stage Breast Cancer (Stage 1-3)
- What is being tested?
- Memantine-HCl
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 30 Oct 2024to Oct 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the detailed description
Up till now, no treatment options are available for prevention of PIPN. Several options have been investigated for treatment of CIPN with only duloxetine had proven benefits. Additional investigations are needed to develop preventive and ameliorative therapy of PIPN.
- Being tested
- Memantine-HCl, Placebo Oral Tablet
- Keywords
- Paclitaxel-induced Toxicity, Breast Cancer patients, Memantine, Neurotoxicity Prevention or treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Memantine-HClDrug
Also called Memantine 20 mg
Memantine hydrochloride 20 mg once daily for 12 weeks.
Placebo Oral TabletDrug
Also called Placebo comparator
A once daily matched tablet of placebo for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Weekly for 12 weeks.
Secondary outcomes (4)
Pain severity
Pain severity will be quantified using the Brief Pain Inventory Short Form (BPI-SF) (Cleeland and Ryan, 1994). It is widely used in both research and clinical settings. Patients will be asked to rate their pain on a numerical scale every cycle. Each scale is presented as a row of equidistant numbers from zero to ten, where zero indicates "no pain" and ten indicates "pain as bad as you can imagine".
Measured: Weekly for 12 weeks.
Patients' QoL
Patients' QoL will be assessed through The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale (FACT/GOG-Ntx) questionnaire. The Ntx subscale is a reliable and valid instrument for assessing the impact of neuropathy on QoL that demonstrates sensitivity to meaningful clinical distinctions and change over time.
It is an eleven-item subscale that evaluates sensory neuropathy, motor neuropathy, hearing neuropathy, and dysfunction associated with CIPN for the previous 7 days. Each question in the Ntx subscale is represented by a Likert scale ranging from zero to four, where zero represents "not at all" and four represents "very much". The Ntx subscale generates a total score that is obtained by the summation of the composing question's scores. The total score ranges from 0 to 44 with higher scores indicating more severe neurotoxicity and worse QoL. The FACT/GOG-Ntx subscale will be evaluated at baseline, at 6 weeks, and 12 weeks.
Measured: baseline, at 6 weeks, and 12 weeks.
Serum levels of nerve growth factor (NGF)
Nerve growth factor, one of major neurotrophins, is known to regulate the growth, maintenance, and survival of neurons. Clinical evidence supports that depletion of NGF occurs during the development of CIPN. In cancer patients receiving taxanes, serum levels of NGF levels were shown to decrease after four to six cycles and decline was associated with the severity of PIPN. For the determination of serum levels of NGF, a blood sample of 4 ml will be collected from every patient.
Measured: Baseline and at 12 weeks.
Severity of depressive symptoms
The effect of memantine on depressive symptoms will be assessed through the nine-items Patient Health Questionnaire (PHQ-9). It is an easy-to-use self-administered questionnaire that reflects each of the nine criteria that the diagnosis of depression is based on according to the Diagnostic and Statistical Manual of Mental Disorders version V (DSM-V) criteria. The score for each question ranges from 0-3, as "0" (not at all) to "3" (nearly every day). The total score is obtained by adding up the individual items' scores. Scores range from 0 to 27 with scores from 0-4 indicating minimal depressive symptoms, 5-9: Mild, 10-14: Moderate, 15-19: Moderately severe, 20-27: Severe.
Measured: Baseline, at 6 weeks, and 12 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2024
- Study start30 Oct 2024
- Primary completionOct 2025 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer Early Stage Breast Cancer (Stage 1-3)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mahmoud Mustafa Mahmoud Gharib, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06679387
- Sponsor's protocol ID
- 45
- Status last verified
- Oct 2024
- First submitted
- 5 Nov 2024
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29254093Argyriou 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.
PubMed 18329278
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "The Effect of Memantine on the Prevention and Amelioration of Paclitaxel-induced Toxicity in Breast Cancer Patients"
- ClinicalTrials.gov ID
- NCT06679387
- Acronym / sponsor ID
- 45
- Keywords
- Paclitaxel-induced Toxicity, Breast Cancer patients, Memantine, Neurotoxicity Prevention or treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 30 Oct 2024 (actual)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 7 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Up till now, no treatment options are available for prevention of PIPN. Several options have been investigated for treatment of CIPN with only duloxetine had proven benefits. Additional investigations are needed to develop preventive and ameliorative therapy of PIPN.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Memantine-HClForty patients who will receive memantine 20 mg once daily in addition to weekly 80 mg/m2 of paclitaxel for 12 weeks. |
| Control arm | Placebo comparator | Drug: Placebo Oral TabletForty patients who will receive placebo once daily in addition to weekly 80 mg/m2 of paclitaxel for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Memantine-HClAlso: Memantine 20 mgMemantine hydrochloride 20 mg once daily for 12 weeks. | Drug | Treatment arm |
| Placebo Oral TabletAlso: Placebo comparatorA once daily matched tablet of placebo for 12 weeks | Drug | Control arm |
Primary outcome
Incidence and grading of paclitaxel induced peripheral neuropathy (PIPN)
Time frame: Weekly for 12 weeks.
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
4 secondary outcomes
Pain severity
Time frame: Weekly for 12 weeks.
Patients' QoL
Time frame: baseline, at 6 weeks, and 12 weeks.
Serum levels of nerve growth factor (NGF)
Time frame: Baseline and at 12 weeks.
Severity of depressive symptoms
Time frame: Baseline, at 6 weeks, and 12 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
- Background: PubMed 29254093Folch 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.
- Background: PubMed 18329278Argyriou 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Memantine-HCl in people with Breast Cancer Early Stage Breast Cancer (Stage 1-3), 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 10 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: looking for participants now, as of the sponsor's last update on 7 Nov 2024. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mahmoud M Gharib, Assistant lecturer (02 01286584470, dr.mahmoudgharib.mg@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and grading of paclitaxel induced peripheral neuropathy (PIPN) (time frame: Weekly for 12 weeks.). 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 NCT06679387, which also lists 2 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 7 Nov 2024.