"Prevention of Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients"

Breast Cancer Female Clinical Trial

Official title:

"Evaluation of the Effect of Pentoxifylline on the Prevention of Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients"

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05189535
• Other study ID #: s2192648
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 3, 2021
• Est. completion date: September 28, 2023

Study information

• Verified date: January 2024
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate the effect of pentoxifylline 400 mg twice daily administration on the prevention of paclitaxel-Induced peripheral neuropathy in breast cancer patients.

Description:

Paclitaxel induced peripheral neuropathy (PIPN) starts early during therapy and may worsen even after cessation and affect mainly sensory neurons. The symptoms of neuropathy include pain, tingling, cold-sensitivity and numbness that typically presents in a stocking glove distribution. The pathogenesis of PIPN may be attributed to drug accumulation in dorsal root ganglia causing increase in inflammatory cytokines, immune mediators and dysregulation of calcium subunits which in turn increases pain. It also causes oxidative stress in sensory axons leading to axon demyelination, increased sensitization to signal transduction, release of pro-inflammatory mediators and activation of apoptosis.

Many animal studies and clinical trials have shown pentoxifylline to have a significant anti-inflammatory and antioxidant effect. It also preserved nerve conduction velocity and ameliorated mechanical hyperalgesia. Pentoxifylline showed a prominent reduction in neuropathic pain in diabetic patients. These effects were mainly due to the ability of pentoxifylline to reduce TNF-α and MDA levels. So, pentoxifylline is a drug of interest due to its ability to ameliorate neuro-inflammation and oxidative stress which play a critical role in PIPN pathogenesis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: September 28, 2023
• Est. primary completion date: September 18, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Adult patients (18-80 years old).

• Female patients.

• Pathologically proved breast cancer.

• Breast cancer patients who will receive adjuvant and neoadjuvant weekly paclitaxel for 12 weeks.

• Eastern Cooperative Oncology Group (ECOG) performance = 2

• Adequate bone marrow function.

• Adequate liver and kidney function.

Exclusion Criteria:

• Patients with preexisting clinical neuropathy.

• Patients with diabetes mellitus.

• Metastatic breast cancer.

• Patients receiving medications that ameliorate neuropathy like; antidepressants, anticonvulsants, opioids, adjuvant or topical analgesics.

• Patients treated with medications that increase the risk of neuropathy.

• Hypersensitivity to pentoxifylline or xanthine derivatives.

• Patients with recent (within 1 month) surgery, myocardial infarction (MI), intracranial or retinal bleeding or active peptic ulcer.

• Patients at high risk for bleeding or taking medications that increase risk of bleeding.

Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms
• Peripheral Nervous System Diseases
• Peripheral Neuropathy

Intervention

Drug:
• Pentoxifylline
Pentoxifylline 400 mg oral tablet twice daily for 12 weeks.
• Paclitaxel
Paclitaxel I.V 80 mg/m2 weekly
• Placebo
placebo

Locations

Country	Name	City	State
Egypt	Ain Shams University hospitals	Cairo	Abbasia

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum tumor necrosis factor alpha (TNF-a)	measuring serum level of tumor necrosis factor using ELISA kit	at baseline and after 12 weeks
Other	Serum malondialdehyde (MDA)	measuring serum level of malondialdehyde.	at baseline and after 12 weeks
Other	The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity(FACT-GOG-NTX) subscale	evaluating the functional difficulties and quality of life related to paclitaxel induced neuropathic symptoms.; score range from (0-44) where lower score indicates more sever symptoms according to the FACT-GOG-NTX scoring guideline.	at baseline, week 1 in each cycle (cycle length is 21 days) up to 12 weeks and at week 12.
Other	Time to develop neuropathy	mean time to develop grade 3 or 4 neuropathy	12 weeks
Primary	Incidence of Paclitaxel induced-peripheral neuropathy	Number of patients reported neuropathy due to paclitaxel	12 weeks
Secondary	Grade of severity of Paclitaxel induced-peripheral neuropathy in patients who developed neuropathy	Severity of neuropathic symptoms will be graded using Common Terminology Criteria for Adverse Events Version 5 (CTCAE v5)	at baseline and on weekly bases for 12 weeks
Secondary	Evaluation of Safety and tolerability of pentoxifylline	side effects reported due to pentoxifylline will be recorded.	evaluation on weekly bases for 12 weeks.
Secondary	The need for dose reduction or drug discontinuation in pentoxifylline and placebo arm.	number of patients who needed dose reduction or drug discontinuation due to paclitaxel induced neuropathy will be recorded.	12 weeks