Atovaquone for Ovarian Cancer

Overseen By Namita Khanna, MD, MSPH

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Emory University

Disqualifiers: Under 18, Pregnant, Incarcerated, 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: 1

Duration: Up to 1 year

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether atovaquone, a medication typically used to prevent certain infections, can treat ovarian cancer that resists standard chemotherapy. Researchers aim to determine if atovaquone can improve outcomes for those with platinum-resistant ovarian cancer, where the cancer worsens within six months after platinum-based treatment. Suitable candidates have high-grade serous ovarian cancer and have experienced disease progression despite recent treatments. Participants will receive atovaquone and undergo regular scans and tests to monitor progress. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that atovaquone is likely to be safe for humans?

Research has shown that people generally tolerate atovaquone well. The FDA has already approved it for treating malaria, indicating its safety for humans. Studies have found that atovaquone can slow ovarian cancer growth in lab tests, which is encouraging. Importantly, when taken orally, most people do not experience serious side effects. This suggests that atovaquone could be a safe option for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Unlike the standard treatments for ovarian cancer, which often include surgery and chemotherapy, atovaquone offers a novel approach by leveraging its unique properties. Atovaquone is typically known for its use as an antiparasitic medication, but researchers are excited about its potential anti-cancer effects, particularly its ability to inhibit cancer cell growth by disrupting mitochondrial function. This mechanism targets cancer cells differently than traditional chemotherapy, which usually attacks rapidly dividing cells indiscriminately. By focusing on a new pathway, atovaquone could offer a promising alternative for patients who might not respond well to existing treatments.

What evidence suggests that atovaquone might be an effective treatment for ovarian cancer?

Research suggests that atovaquone, which participants in this trial will receive, might help treat ovarian cancer. Studies have shown that atovaquone can slow the growth of ovarian cancer cells in lab tests and animals. It interferes with cancer cells' energy production, making it harder for them to grow and spread. Some studies also found that atovaquone made cancer cells more noticeable to the immune system, potentially aiding the body's fight against cancer. Although typically used to treat infections, these findings indicate that atovaquone might also serve as a cancer treatment. ^{1 2 6 7 8}

Who Is on the Research Team?

Namita Khanna, MD, MSPH

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with high-grade serous ovarian cancer that has worsened within six months after platinum-based chemotherapy. Participants must be in good physical condition (ECOG status of 0 or 1) and can have had any number of prior treatments. The study welcomes non-English speakers and referrals from community practices.

Inclusion Criteria

My ovarian cancer got worse within 6 months after my last platinum-based treatment.

I have had any number of previous treatments.

I do not speak English.

Exclusion Criteria

I am under 18 years old.

Patients who are incarcerated

I am unable to make my own medical decisions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atovaquone orally and undergo CT and biopsy or paracentesis throughout the study

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person)

Long-term follow-up

Participants are followed up every 6 months after the initial follow-up period

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Atovaquone

Trial Overview

The trial is evaluating the effectiveness of Atovaquone, an antiprotozoal medication typically used to prevent pneumonia, as a new treatment option for patients with platinum-resistant ovarian cancer. It involves procedures like paracentesis, biopsy, and CT scans to monitor the disease's response.

How Is the Trial Designed?

Group I: Treatment (atovaquone) Experimental Treatment 4 Interventions

Patients receive atovaquone PO on study. Patients also undergo CT and biopsy or paracentesis throughout the study.

Atovaquone is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as Mepron for:

• Pneumocystis jirovecii pneumonia (PCP)
• Plasmodium falciparum malaria

Approved in European Union as Malarone for:

• Plasmodium falciparum malaria
• Pneumocystis jirovecii pneumonia (PCP)

Approved in United Kingdom as Wellvone for:

• Pneumocystis jirovecii pneumonia (PCP)
• Plasmodium falciparum malaria

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

Patients with recurrent ovarian cancer are categorized as either platinum-sensitive or platinum-resistant, which influences treatment options; platinum-sensitive patients often benefit from re-treatment with paclitaxel/platinum combinations, while platinum-resistant patients may receive single-agent therapies like altretamine or topotecan.

For platinum-sensitive patients with minimal residual disease, intensive intraperitoneal therapy with cisplatin and paclitaxel shows the most promise for long-term disease-free survival, highlighting the importance of tailored treatment strategies based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory and recurrent ovarian cancer. Alberts, DS.[2005]

In a study involving 40 female Wistar-Albino rats, edaravone demonstrated protective effects against ovarian injury caused by cisplatin, as indicated by lower levels of malondialdehyde (MDA) and nitric oxide (NO) compared to the cisplatin-only group.

Histopathological analysis showed significantly less ovarian tissue damage, DNA damage, and apoptosis in the group treated with both cisplatin and edaravone, suggesting that edaravone effectively mitigates the harmful effects of cisplatin on ovarian health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective effect of edaravone on cisplatin-induced injury in rat ovary. Kara, O., Kaymak, E., Yakan, B.[2022]

Anetumab ravtansine, a mesothelin-targeting antibody-drug conjugate, demonstrated strong antitumor activity in ovarian cancer models with high mesothelin expression, but showed no effect in mesothelin-negative models, indicating its targeted mechanism of action.

The combination of anetumab ravtansine with other treatments like pegylated liposomal doxorubicin and copanlisib resulted in enhanced antitumor effects in both cell line and patient-derived xenograft models, and all combinations were well-tolerated, suggesting a promising avenue for combination therapy in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anetumab ravtansine inhibits tumor growth and shows additive effect in combination with targeted agents and chemotherapy in mesothelin-expressing human ovarian cancer models. Quanz, M., Hagemann, UB., Zitzmann-Kolbe, S., et al.[2023]

Bevacizumab, an anti-VEGF therapy, has shown efficacy in treating epithelial ovarian cancers, both as a standalone treatment and in combination with other therapies, based on evidence from Phase II trials involving various patient populations.

While most side effects of bevacizumab, such as proteinuria and hypertension, are mild and manageable, there are serious but rare risks like arterial thromboembolism and gastrointestinal perforation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with bevacizumab in the management of epithelial ovarian cancer. Burger, RA.[2015]

In a study of 51 patients with platinum-resistant epithelial ovarian cancer, long-term low-dose oral etoposide showed a partial response in 17.6% of patients and a stable response in 25.5%, with a median overall survival of 16.4 months.

The treatment was generally well-tolerated, with 37.3% of patients experiencing mild to moderate hematologic toxicity and 29.4% experiencing gastrointestinal toxicity, indicating that while there are some side effects, the overall safety profile is acceptable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral etoposide for platinum-resistant and recurrent epithelial ovarian cancer: a study by the Anatolian Society of Medical Oncology. Kucukoner, M., Isikdogan, A., Yaman, S., et al.[2022]

Docetaxel has shown comparable effectiveness to paclitaxel when combined with carboplatin for treating advanced ovarian cancer, with a potentially better safety profile.

Current treatments for platinum-resistant ovarian cancer are limited, and while some experimental therapies targeting the epidermal growth factor receptor show promise, more research is needed to find effective new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. Costa, SD., von Minckwitz, G., Wernicke, K., et al.[2008]

The combination of docetaxel, oxaliplatin, and bevacizumab as a first-line treatment for advanced ovarian, peritoneal, or fallopian tube cancer showed a promising 12-month progression-free survival rate of 65.7% among 132 patients, with a median progression-free survival of 16.3 months.

The treatment was generally safe, with the most common severe side effects being neutropenia and leukopenia, and only one reported fatal gastrointestinal perforation, indicating no unexpected safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube. Herzog, TJ., Monk, BJ., Rose, PG., et al.[2021]

In patients with ovarian cancer who relapse after initial chemotherapy, five key agents—topotecan, oral etoposide, liposomal doxorubicin, gemcitabine, and possibly docetaxel—show significant effectiveness against platinum- and paclitaxel-resistant disease.

Additional treatments, including vinorelbine, tamoxifen, and others, may also be beneficial for patients resistant to platinum-based therapies, highlighting the need for personalized treatment strategies in managing ovarian cancer relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy for ovarian cancer. Garcia, AA.[2019]

In a phase 3 trial involving 682 patients with recurrent ovarian cancer, the combination of carboplatin-pegylated liposomal doxorubicin and bevacizumab showed a median progression-free survival of 13.3 months, significantly longer than the 11.6 months observed with the standard carboplatin-gemcitabine-bevacizumab regimen (p=0.012).

The safety profile was comparable between the two treatment groups, with hypertension and neutropenia being the most common severe adverse events; however, treatment-related deaths were rare, occurring in less than 1% of patients in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Pfisterer, J., Shannon, CM., Baumann, K., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9102822/

Atovaquone: An Inhibitor of Oxidative Phosphorylation as ...

The daily administration of atovaquone (200 mg/kg) via oral gavage over a 15-day period resulted in a significant reduction in tumor volume ( ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0344033821001904

Atovaquone at clinically relevant concentration overcomes ...

In line with in vitro findings, atovaquone alone at non-toxic dose is effective in inhibiting ovarian cancer growth in vivo, and its combination with cisplatin ...

3.

jitc.bmj.com

jitc.bmj.com/content/12/Suppl_2/A880

776 Atovaquone upregulates PD-L1 expression via ...

Previously our lab has shown that atovaquone, a known anti-malarial drug, reduces ovarian cancer proliferation under in vitro and in vivo ...

4.

reporter.nih.gov

reporter.nih.gov/project-details/10824296

Repurposing Atovaquone for Preventing Ovarian Cancer

Atovaquone is currently FDA approved for the treatment of malaria, and is a well-tolerated, orally available medication. It slows ovarian cancer growth in vitro ...

5.

aacrjournals.org

aacrjournals.org/cancerres/article/83/7_Supplement/6395/719108/Abstract-6395-Atovaquone-promotes-release-of

Abstract 6395: Atovaquone promotes release of damage ...

Atovaquone promotes release of damage-associated molecular patterns from epithelial ovarian cancer cells [abstract]. In: Proceedings of the ...

6.

aacrjournals.org

aacrjournals.org/cancerres/article/85/8_Supplement_1/527/754867/Abstract-527-Atovaquone-upregulates-PD-L1

Abstract 527: Atovaquone upregulates PD-L1 expression via ...

Flow cytometry data demonstrated a (20-55%) increase in the level of PDL1 expression after 48h to 72 h atovaquone treatment in OVCAR 5 and ID8 ...

7.

clinicaltrials.eu

clinicaltrials.eu/inn/atovaquone/

Atovaquone: A Comprehensive Guide for Patients

Studies have shown that atovaquone can significantly reduce oxygen consumption in various tumor cell lines, which may lead to decreased tumor hypoxia (low ...

8.

nature.com

nature.com/articles/s41420-020-00343-6

The anti-malarial drug atovaquone potentiates platinum ...

Here, we repurpose atovaquone (ATQ), a well-tolerated & FDA-approved anti-malarial agent by demonstrating that it potentiates cancer cell death ...