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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods to prevent numbness, pain, or tingling in the hands and feet, side effects some people experience from the cancer drug paclitaxel. The trial explores whether cryocompression therapy (cooling wraps) alone or combined with cilostazol (a drug that improves blood flow) can prevent these symptoms in patients with gynecological cancers, such as uterine or ovarian cancer. Individuals diagnosed with these cancers and about to begin a treatment plan including paclitaxel may be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that cryocompression is safe and generally well-received by patients. Studies have found it effective in reducing side effects like numbness and pain in the hands and feet during chemotherapy. Patients have expressed satisfaction with this therapy, and no major safety concerns have emerged.

Regarding cilostazol, research suggests it is also safe and tolerable when used with cryocompression. Studies indicate that cilostazol can reduce the risk of severe peripheral neuropathy, which is nerve damage that causes pain or numbness, in chemotherapy patients. As a result, fewer patients experienced serious numbness and pain.

Both treatments aim to ease the impact of chemotherapy on the body by reducing side effects. While larger studies are still needed, current findings are promising for safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore innovative ways to enhance the effectiveness of paclitaxel, a common chemotherapy drug for gynecological cancers. The combination of cryocompression and cilostazol offers a novel approach by potentially improving drug delivery and minimizing side effects. Cryocompression involves using cooling compression wraps to reduce inflammation and pain, which might enhance patient comfort during treatment. Additionally, cilostazol, a medication usually used to improve blood flow, could help in increasing the delivery of paclitaxel to cancer cells, potentially boosting its effectiveness. These strategies represent a promising shift from the standard chemotherapy protocols, aiming to improve patient outcomes and quality of life during treatment.

What evidence suggests that this trial's treatments could be effective for preventing paclitaxel-induced peripheral neuropathy in gynecologic cancer patients?

Research has shown that cryocompression therapy, which participants in this trial may receive, can help reduce the risk of numbness and tingling in the hands and feet caused by chemotherapy. One study found that cryocompression lowered the chance of severe symptoms by 46%, resulting in fewer patients experiencing serious issues. In this trial, some participants will receive cryocompression therapy alone, while others will receive it in combination with cilostazol. Studies suggest that cilostazol, a medication that improves blood flow, may help prevent nerve problems caused by the chemotherapy drug paclitaxel. Using cryocompression with cilostazol might offer extra protection by cooling the area and improving blood circulation. ^{2 5 6 7 8}

Who Is on the Research Team?

Susan C Modesitt

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

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.

Hypersensitivity (e.g. anaphylaxis, angioedema) to cilostazol or any components of cilostazol

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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, 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]

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]

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 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]

Citations

1. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/phar.2830

Effect of cilostazol on preventing paclitaxel‐induced ... Adjunctive use of cilostazol is as a novel option that might reduce the incidence of paclitaxel-induced peripheral neuropathy and improve the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32456565/

Cilostazol protects against cyclophosphamide-induced ... Conclusions: These data suggest that cilostazol protects against CP- induced ovarian damage, which may be related to an increase in cAMP with subsequent anti- ...

3. researchgate.net researchgate.net/publication/341674435_Cilostazol_protects_against_cyclophosphamide-induced_ovarian_toxicity_in_female_rats_role_of_cAMP_and_HO-1

Cilostazol protects against cyclophosphamide-induced ... Conclusions: These data suggest that cilostazol protects against CP- induced ovarian damage, which may be related to an increase in cAMP ...

4. link.springer.com link.springer.com/article/10.1007/s00018-018-2954-1

and taxane-based chemotherapy of ovarian cancer affects ... In this review, we summarize effects of selected drugs used to treat ovarian cancer (platin derivatives—cisplatin and carboplatin; and taxanes— ...

5. clinconnect.io clinconnect.io/trials/NCT06492070

Cryocompression With or Without Cilostazol for the The phase II trial evaluates the effectiveness of cryocompression therapy alone or in combination with cilostazol in preventing paclitaxel-induced ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03905

Cryocompression with or without Cilostazol for the ... Giving cilostazol together with cryocompression may be safe and tolerable in treating patients with gynecological cancers. Eligibility Criteria. Inclusion ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37199288/

Effect of cilostazol on preventing paclitaxel-induced ... Adjunctive use of cilostazol is as a novel option that might reduce the incidence of paclitaxel-induced peripheral neuropathy and improve the patients' QoL.

8. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0030649

The Role of Cilostazol, a Phosphodiesterase 3 Inhibitor, on ... Based on in vitro studies, we injected cilostazol into female mice to evaluate its role in the suppression and inhibition of oocyte maturation and pregnancy.