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

Trial Summary

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 Atovaquone safe for use in humans?

There is no specific safety data available for Atovaquone in the context of ovarian cancer from the provided research articles. However, Atovaquone is generally used as an anti-malarial and anti-parasitic medication, and its safety profile is well-established for these uses, with common side effects including nausea, diarrhea, and headache. ^{1 2 3 4 5}

How is the drug Atovaquone unique in treating ovarian cancer?

Atovaquone is unique for ovarian cancer treatment as it is traditionally used for infections like malaria and pneumonia, suggesting a novel approach compared to standard chemotherapy drugs. Its use in ovarian cancer is experimental, potentially offering a different mechanism of action from typical chemotherapy agents. ^{2 6 7 8 9}

What is the purpose of this trial?

This phase II trial test tests how well repurposing atovaquone works in treating patients with platinum-resistant ovarian cancer. Atovaquone is used for the treatment or prevention of certain infections. Atovaquone is in a class of medications called antiprotozoal agents. It works by stopping the growth of certain types of protozoa that can cause pneumonia. Giving atovaquone may be effective in treating platinum-resistant ovarian cancer and result in improved outcomes compared to standard chemotherapy regimens.

Research Team

Namita Khanna, MD, MSPH

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Protective effect of edaravone on cisplatin-induced injury in rat ovary. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. [2008]

3. United States 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. [2021]

4. Thailand pubmed.ncbi.nlm.nih.gov

Oral etoposide for platinum-resistant and recurrent epithelial ovarian cancer: a study by the Anatolian Society of Medical Oncology. [2022]

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

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

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

Treatment of refractory and recurrent ovarian cancer. [2005]

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

Salvage therapy for ovarian cancer. [2019]

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

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. [2022]

9. United States 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. [2023]