Cryocompression + Cilostazol for Gynecological Cancers

Recruiting at 2 trial locations

Overseen By Sharese Windley

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Antiplatelet therapies

Disqualifiers: Diabetes, Hepatic impairment, Raynaud's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 31

Duration: 18-27 weeks

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on antiplatelet therapies other than acetylsalicylic acid, you may not be eligible to participate.

What data supports the effectiveness of the drug paclitaxel for treating gynecological cancers?

Paclitaxel, also known as Taxol, is a drug that has been shown to be effective in treating several types of cancer, including ovarian cancer, which is a type of gynecological cancer. It works by stabilizing microtubules, which are structures in cells, and this action helps to kill cancer cells. ^{1 2 3 4 5}

Is the combination of cryocompression and cilostazol safe for treating gynecological cancers?

Paclitaxel, a drug used in this treatment, can cause side effects like hypersensitivity reactions, which have been reduced with premedication, and neutropenia (low white blood cell count). Abraxane, a form of paclitaxel, has shown improved safety in patients with severe reactions. No specific safety data for cryocompression or cilostazol in this context is provided. ^{2 5 6 7 8}

What makes the Cryocompression + Cilostazol treatment for gynecological cancers unique?

This treatment is unique because it combines cryocompression (a method that uses cold and pressure) with cilostazol (a drug that improves blood flow) alongside paclitaxel, which is a drug that stabilizes microtubules in cancer cells to prevent them from dividing. This combination may offer a novel approach to enhance the effectiveness of paclitaxel in treating gynecological cancers. ^{1 2 3 9 10}

What is the purpose of this trial?

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.

Research Team

Susan C Modesitt

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for patients with various gynecological cancers who are undergoing treatment with paclitaxel, a chemotherapy drug. Participants should not have pre-existing conditions that would interfere with the study or pose additional risk.

Inclusion Criteria

I have been diagnosed with a specific type of cancer and am planning to undergo a specific chemotherapy regimen.

I have completed 6-9 cycles of chemotherapy for my cancer in the last 3 months.

I can take care of myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

I need medication for nerve pain caused by chemotherapy.

My diabetes is not well-controlled, with an A1c over 7.0.

I am willing and able to follow all study requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive paclitaxel infusion and cryocompression therapy, with or without cilostazol, for up to 6-9 cycles

18-27 weeks

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

12 months

Follow-up at 30 days, 6 months, and 12 months

Treatment Details

Interventions

• Cilostazol
• Cryocompression Therapy
• Paclitaxel

Trial Overview The effectiveness of cryocompression therapy alone or combined with cilostazol in preventing numbness, pain, or tingling caused by paclitaxel in patients with gynecologic cancers is being tested.

Participant Groups

Group I: Arm A (cryocompression and cilostazol) Experimental Treatment 4 Interventions

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.

Group II: Arm 2 (cryocompression) Experimental Treatment 3 Interventions

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.

Group III: Arm C (standard of care) Active Control 2 Interventions

Patients undergo standard of care throughout the study.

Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Paclitaxel is a cytotoxic drug that belongs to the taxane group and is specifically approved for treating metastatic ovarian carcinoma after standard platinum-based therapies have not been effective.

It represents a new treatment option for patients with advanced ovarian cancer, providing an alternative when traditional therapies fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel for ovarian cancer. [2015]

Paclitaxel, a drug used to treat various cancers, has traditionally been known to cause cell death by inducing mitotic arrest, but new evidence suggests that it may actually lead to multipolar cell divisions due to low intratumoral concentrations.

This new understanding of paclitaxel's mechanism of action could help develop a biomarker to identify the approximately 50% of patients who are likely to benefit from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How Taxol/paclitaxel kills cancer cells. Weaver, BA.[2022]

A brief exposure to low-intensity ultrasound waves can prevent the cytotoxic effects of paclitaxel on cancer cells by disrupting the microtubule cytoskeleton, which is crucial for the drug's mechanism of action.

This study suggests that ultrasound treatment can lead to the disassembly of paclitaxel-induced rigid microtubule bundles, allowing for the formation of a new microtubule network and potentially reducing the side effects of paclitaxel in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells. Amaya, C., Luo, S., Baigorri, J., et al.[2021]

Paclitaxel (Taxol) is a significant new chemotherapy drug for breast cancer, showing promise in both single-agent and combination treatments.

Ongoing research at Memorial Sloan-Kettering Cancer Center aims to optimize the use of paclitaxel in various treatment settings, including metastatic and adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. Seidman, AD., Hudis, CA., Fennelly, D., et al.[2015]

Paclitaxel (TAXOL) is an effective chemotherapy drug that works by disrupting microtubule function, showing significant activity against advanced ovarian, breast, and non-small cell lung cancers, among others.

With proper premedication, the incidence of hypersensitivity reactions to paclitaxel has been reduced to 3%, although neutropenia remains a major dose-limiting side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Paclitaxel (Taxol)]. Hájek, R.[2015]

Paclitaxel, a novel antineoplastic drug, has shown significant effectiveness in treating advanced cancers such as ovarian, breast, non-small cell lung cancer, and head and neck cancer, with a potential to become a first-line treatment when combined with platinum for advanced ovarian cancer.

While initial hypersensitivity reactions posed challenges, current premedication strategies have reduced these side effects to less than 3%, although neutropenia remains a major dose-limiting adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. Hájek, R., Vorlicek, J., Slavik, M.[2015]

In a study of 60 patients with relapsed non-Hodgkin's lymphoma (NHL), 23% achieved either a partial or complete remission after receiving a 3-hour infusion of 200 mg/m2 of Paclitaxel (Taxol) every 3 weeks, indicating its efficacy as a treatment option.

The treatment was well-tolerated with no allergic reactions or cardiac toxicity reported, although common side effects included hair loss (100%), peripheral neuropathy (37%), and myalgia (25%), suggesting that Taxol can be safely administered in an outpatient setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-hour paclitaxel infusion in patients with refractory and relapsed non-Hodgkin's lymphoma. Younes, A., Sarris, A., Melnyk, A., et al.[2017]

Abraxane, a Cremophor-free formulation of paclitaxel, was well tolerated by five patients with gynecologic cancers who previously had hypersensitivity reactions to standard paclitaxel, indicating its potential safety in this population.

The case reports suggest that Abraxane may be a viable alternative for treating gynecologic malignancies, as all patients experienced no adverse reactions or major side effects, warranting further investigation into its clinical efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane for the treatment of gynecologic cancer patients with severe hypersensitivity reactions to paclitaxel. Fader, AN., Rose, PG.[2018]

Intraperitoneal administration of paclitaxel has shown a significant pharmacokinetic advantage, with over 1,000-fold greater exposure in the peritoneal cavity compared to systemic delivery, making it a promising option for treating ovarian cancer.

A phase II trial is currently underway to evaluate the effectiveness of intraperitoneal paclitaxel in ovarian cancer patients, focusing on whether higher concentrations and longer exposure can lead to better tumor cell kill and improved patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal paclitaxel in the management of ovarian cancer. Markman, M.[2015]

Taxanes, specifically paclitaxel and docetaxel, are crucial in treating gynecologic cancers such as those of the ovary, uterus, and cervix, often used alongside platinum-based drugs for enhanced effectiveness.

While taxanes can provide significant palliative benefits as single agents, there are still many unanswered questions regarding the best delivery methods, treatment duration, and the potential benefits of regional administration of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxanes in the management of gynecologic malignancies. Markman, M.[2008]

References

1. England pubmed.ncbi.nlm.nih.gov

Paclitaxel for ovarian cancer. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

How Taxol/paclitaxel kills cancer cells. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. [2015]

5. Czech Republic pubmed.ncbi.nlm.nih.gov

[Paclitaxel (Taxol)]. [2015]

6. Slovakia pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Three-hour paclitaxel infusion in patients with refractory and relapsed non-Hodgkin's lymphoma. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Abraxane for the treatment of gynecologic cancer patients with severe hypersensitivity reactions to paclitaxel. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Intraperitoneal paclitaxel in the management of ovarian cancer. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Taxanes in the management of gynecologic malignancies. [2008]