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

Sponsor
Ain Shams University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05189535
Collaborator
(none)
60
1
2
9.9
6

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A prospective, randomized, placebo controlledA prospective, randomized, placebo controlled
Masking:
Single (Participant)
Masking Description:
single blinded
Primary Purpose:
Prevention
Official Title:
"Evaluation of the Effect of Pentoxifylline on the Prevention of Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients"
Actual Study Start Date :
Oct 3, 2021
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Aug 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: pentoxifylline 400 mg

Patients will receive paclitaxel 80 mg/m2 once per week for 12 weeks and pentoxifylline 400 mg twice daily for the paclitaxel treatment period.

Drug: Pentoxifylline
Pentoxifylline 400 mg oral tablet twice daily for 12 weeks.
Other Names:
  • Trental
  • Drug: Paclitaxel
    Paclitaxel I.V 80 mg/m2 weekly
    Other Names:
  • Taxol
  • Placebo Comparator: Placebo

    Patients will receive paclitaxel 80 mg/m2 once per week for 12 weeks and placebo twice daily for the paclitaxel treatment period..

    Drug: Paclitaxel
    Paclitaxel I.V 80 mg/m2 weekly
    Other Names:
  • Taxol
  • Drug: Placebo
    placebo

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of Paclitaxel induced-peripheral neuropathy [12 weeks]

      Number of patients reported neuropathy due to paclitaxel

    Secondary Outcome Measures

    1. Grade of severity of Paclitaxel induced-peripheral neuropathy in patients who developed neuropathy [at baseline and on weekly bases for 12 weeks]

      Severity of neuropathic symptoms will be graded using Common Terminology Criteria for Adverse Events Version 5 (CTCAE v5)

    2. Evaluation of Safety and tolerability of pentoxifylline [evaluation on weekly bases for 12 weeks.]

      side effects reported due to pentoxifylline will be recorded.

    3. The need for dose reduction or drug discontinuation in pentoxifylline and placebo arm. [12 weeks]

      number of patients who needed dose reduction or drug discontinuation due to paclitaxel induced neuropathy will be recorded.

    Other Outcome Measures

    1. Serum tumor necrosis factor alpha (TNF-α) [at baseline and after 12 weeks]

      measuring serum level of tumor necrosis factor using ELISA kit

    2. Serum malondialdehyde (MDA) [at baseline and after 12 weeks]

      measuring serum level of malondialdehyde.

    3. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity(FACT-GOG-NTX) subscale [at baseline and before each cycle (cycle length is 21 days) up to 12 weeks]

      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.

    4. Time to develop neuropathy [12 weeks]

      mean time to develop grade 3 or 4 neuropathy

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ain Shams University hospitals Cairo Abbasia Egypt 11566

    Sponsors and Collaborators

    • Ain Shams University

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sondos Sherif Ismail, Clinical Pharmacy, Ain Shams University, Ain Shams University
    ClinicalTrials.gov Identifier:
    NCT05189535
    Other Study ID Numbers:
    • s2192648
    First Posted:
    Jan 12, 2022
    Last Update Posted:
    Jan 12, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Sondos Sherif Ismail, Clinical Pharmacy, Ain Shams University, Ain Shams University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 12, 2022