Cryocompression With or Without Cilostazol for the Prevention of Paclitaxel-induced Neuropathy in Patients With Gynecological Cancers

Prevention of Paclitaxel-Induced Peripheral Neuropathy: Randomized Trial of Cryocompression With or Without Cilostazol

The phase II trial evaluates the effectiveness of cryocompression therapy alone or in combination with cilostazol in preventing paclitaxel-induced peripheral neuropathy (numbness, pain or tingling in the feet and hands) for patients with gynecologic cancers. Peripheral neuropathy is a common side effect of many chemotherapeutic agents, including paclitaxel. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Cryocompression is a therapy that combines compression garments or dressings with cooling of the treated area. Cilostazol is in a class of medications called platelet-aggregation inhibitors (antiplatelet medications). It works by improving blood flow to the legs. Giving cilostazol together with cryocompression may be safe and tolerable in treating patients with gynecological cancers.

Study Overview

• Status: Recruiting
• Conditions: Malignant Solid Neoplasm; Fallopian Tube Carcinoma; Cervical Carcinoma; Ovarian Carcinoma; Malignant Uterine Neoplasm; Vulvar Carcinoma; Primary Peritoneal Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Best Practice; Device: Cryocompression Therapy; Drug: Paclitaxel; Drug: Cilostazol

Detailed Description

PRIMARY OBJECTIVES:

I. To quantify the incidence and severity of peripheral neuropathy in women treated with paclitaxel for gynecologic malignancies in conjunction with cryocompression and to assess the impact of cilostazol on the development of peripheral neuropathy. (ARM A and ARM B) II. To quantify the baseline post-chemotherapy neuropathy rates among patients with gynecologic malignancies following standard clinical care practices according to their treating physician. (ARM C)

SECONDARY OBJECTIVES:

I. To estimate the potential impact of cilostazol on quality of life related to chemotherapy-induced peripheral neuropathy.

II. To estimate the potential impact of cilostazol on the need for pharmacologic symptom management for peripheral neuropathy.

III. To estimate the potential impact of cilostazol on chemotherapy dose reductions and delays due to peripheral neuropathy.

IV. To assess the safety of using cilostazol in conjunction with chemotherapy regimens with platinum/paclitaxel with or without VEGF inhibition, with or without immunotherapy, and with or without HER2-directed therapy.

OUTLINE: Participants are assigned to 1 of 3 arms.

ARM A: Patients receive paclitaxel infusion once daily (QD) and receive cryocompression therapy with cooling compression wraps three times daily (TID) over 15 minutes before, during, and after receiving paclitaxel infusion on day 1 of each cycle. Patients also receive cilostazol orally (PO) twice daily (BID) beginning with their first paclitaxel infusion continuing until 2 weeks after the final paclitaxel infusion. Treatment with paclitaxel continues for up to 6-9 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive paclitaxel infusions QD and receive cryocompression therapy with cooling compression wraps TID for 15 minutes before, during, and after receiving paclitaxel infusions on day 1 of each cycle. Treatment with paclitaxel continues for up to 6-9 cycles in the absence of disease progression or unacceptable toxicity.

ARM C: Patients undergo standard of care throughout the study.

After completion of study treatment, patients are followed up at 30 days and then up to 1 year.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Susan Modesitt, MD; Phone Number: 404-727-9578; Email: smodesi@emory.edu
• Study Contact Backup: Name: Sharese Windley; Phone Number: 404-778-8778; Email: sharese.windley@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Recruiting
      • Emory University Hospital Midtown
      • Contact: Susan Modesitt, MD; Phone Number: 404-727-9578; Email: smodesi@emory.edu
    • Atlanta, Georgia, United States, 30342
      • Not yet recruiting
      • Emory Saint Joseph's Hospital
      • Contact: Susan Modesitt, MD; Phone Number: 404-727-9578; Email: smodesi@emory.edu
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Emory University Hospital/Winship Cancer Institute
      • Principal Investigator: Susan C. Modesitt
      • Contact: Susan C. Modesitt; Phone Number: 404-727-9578; Email: smodesi@emory.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• INCLUSION CRITERIA FOR ARMS A and B:
• Age 18 years or older
• Diagnosis of uterine, ovarian/fallopian tube/primary peritoneal, cervical, or vulvar cancer and planned chemotherapy regimen of 6-9 cycles of paclitaxel and carboplatin or cisplatin with or without VEGF inhibition, with or without immunotherapy, and with or without HER2-directed therapy
• Eastern Cooperative Oncology Group performance status from 0 to 2
• ARM C: Age 18 years or older
• ARM C: Diagnosis of uterine, ovarian/fallopian tube/primary peritoneal, cervical, or vulvar cancer and completion of 6-9 cycles of a chemotherapy regimen consisting of paclitaxel and carboplatin or cisplatin with or without VEGF inhibition, with or without immunotherapy, and with or without HER2-directed therapy within the last 3 months
• ARM C: Eastern Cooperative Oncology Group performance status from 0 to 2

Exclusion Criteria:

• EXCLUSION CRITERIA FOR ARMS A and B:
• Any patient unable and/or unwilling to cooperate with all study protocols
• Previous treatment with paclitaxel
• Patients with baseline pre-chemotherapy neuropathy requiring pharmacologic treatment
• Diabetes mellitus with hemoglobin A1c >7.0

• Hepatic impairment, moderate to severe (Class B & C by Child-Pugh score)

  • Slight or moderate malignant ascites alone will not be considered indicative of hepatic impairment in the absence of other evidence of hepatic disease
• Raynaud's phenomenon
• Active wounds on the hands or feet
• High risk uncontrolled arrhythmias
• Ischemic heart disease
• Inadequate bone marrow function with white blood count < 4,000/mm^3 and platelet count < 100,000/mm^3
• Inadequate liver function with serum total bilirubin >= 1.5mg/dL
• Inadequate renal function with serum creatinine >= 1.5mg/dL
• On one or more antiplatelet therapies excluding acetylsalicylic acid
• Hypersensitivity (e.g. anaphylaxis, angioedema) to cilostazol or any components of cilostazol

• Pregnant and nursing patients

  • Patients enrolled in this study who have the potential to become pregnant (have an intact uterus, ovary(ies), and fallopian tube(s), have not entered menopause, and have regular menses) are required to utilize reliable contraception such as celibacy, hormonal contraception (oral pills, implant, injection, ring or patch), intrauterine device (IUD), condom and/or diaphragm with spermicide
• Incarcerated patients
• Patients unable to consent for themselves, due to cognitive impairment or other reason
• Patients with contraindications to cilostazol
• Any patient who does not meet criteria to receive chemotherapy
• ARM C: Any patient unable and/or unwilling to cooperate with all study protocols
• ARM C: Previous treatment with paclitaxel
• ARM C: Patients with baseline pre-chemotherapy neuropathy requiring pharmacologic treatment
• ARM C: Diabetes mellitus with hemoglobin A1c >7.0
• ARM C: Pregnant patients
• ARM C: Incarcerated patients
• ARM C: Patients unable to consent for themselves, due to cognitive impairment or other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 2 (cryocompression); Patients receive paclitaxel infusions QD and receive cryocompression therapy with cooling compression wraps TID for 15 minutes before, during, and after receiving paclitaxel infusions on day 1 of each cycle. Treatment with paclitaxel continues up to 6-9 cycles in the absence of disease progression or unacceptable toxicity.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Device: Cryocompression Therapy; Undergo cryocompression therapy; Drug: Paclitaxel; Given by infusion; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat
Experimental: Arm A (cryocompression and cilostazol); Patients receive paclitaxel infusion QD and receive cryocompression therapy with cooling compression wraps TID over 15 minutes before, during, and after receiving paclitaxel infusion on day 1 of each cycle. Patients also receive cilostazol PO BID beginning with their first paclitaxel infusion continuing until 2 weeks after the final paclitaxel infusion. Treatment with paclitaxel continues for up to 6-9 cycles in the absence of disease progression or unacceptable toxicity.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Device: Cryocompression Therapy; Undergo cryocompression therapy; Drug: Paclitaxel; Given by infusion; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Cilostazol; Given PO; Other Names: Pletal
Active Comparator: Arm C (standard of care); Patients undergo standard of care throughout the study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Best Practice; Undergo standard of care; Other Names: standard of care; standard therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in sensation and vibration objective neuropathy scores (Arms A and B)	Specifically, the primary outcome will be the proportion of patients with abnormal vibration sensation times on at least one great toe or index finger assessed by a validated Neuropathy Assessment instrument. Will be compared between treatment groups (Arms A and B) using a chi-square test of independence.	At 1 month post chemotherapy completion and at 6 months and 12 months
Rates of impaired sensation and vibration on objective neuropathy testing and ≥ Grade 2 neuropathy among patients who recently completed paclitaxel treatment with standard of care treatment protocols (Arm C)	The proportion of patients in Arm C will be tabulated with associated Clopper-Pearson 95% confidence intervals.	At 1 month post chemotherapy completion and at 6 months and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in sensation and vibration objective neuropathy scores	Specifically, the outcome of interest will be the proportion of patients with abnormal vibration sensation times on at least one great toe or index finger assessed by a validated Neuropathy Assessment instrument. Will be compared between treatment groups using a chi-square test of independence.	At 1 month post chemotherapy completion and at 6 months and 12 months
Difference in >= grade 2 neuropathy between the two study arms	Will be compared between treatment groups using a chi-square test of independence.	At 1 month post chemotherapy completion and at 6 months and 12 months
Changes in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group- Neurotoxicity (FACT/GOG-NTX) scores	Will be compared between treatment groups using a chi-square test of independence, as will the proportion of patients experiencing a clinically significant change in FACT/GOG-O-NTX neuropathy scores. Proportion of patients with a clinically significant change in scores (change of 10% or more from baseline) will also be determined.	At 1 month post chemotherapy completion and at 6 months and 12 months
Differences in the rate of patients starting new pharmacologic therapy for peripheral neuropathy while receiving paclitaxel chemotherapy		At 1 month post chemotherapy completion and at 6 months and 12 months
Differences in the rate of patients requiring paclitaxel dose reductions or chemotherapy delays due to peripheral neuropathy		At 1 month post chemotherapy completion and at 6 months and 12 months
Rate of grade 3 adverse events	Will be tabulated by group according to Common Terminology Criteria for Adverse Events Grade, System Organ Class and relation to study treatment.	At 1 month post chemotherapy completion and at 6 months and 12 months

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Susan C Modesitt, Emory University Hospital/Winship Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 21, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Uterine Cervical Diseases; Vulvar Diseases; Fallopian Tube Diseases; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Uterine Cervical Neoplasms; Vulvar Neoplasms; Fallopian Tube Neoplasms; Uterine Neoplasms; Health Services Administration; Health Care Quality, Access, and Evaluation; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Quality of Health Care; Quality Indicators, Health Care; Taxoids; Cyclodecanes; Diterpenes; Quinolines; Guidelines as Topic; Quality Assurance, Health Care; Albumins; Tetrazoles; Albumin-Bound Paclitaxel; Cilostazol; Paclitaxel; Standard of Care; Practice Guidelines as Topic
• Other Study ID Numbers: STUDY00007242 (Other Identifier: Emory University Hospital/Winship Cancer Institute); P30CA138292 (U.S. NIH Grant/Contract); NCI-2024-03905 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); Winship6141-24 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No