Statin Therapy for Ovarian Cancer

Overseen By Amy Oppenheim

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: Bobbie Jo Rimel, MD

Must not be taking: Statins, Investigational agents

Disqualifiers: Liver disease, Chronic myopathy, HIV, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether simvastatin, a drug typically used to lower cholesterol, can slow or stop the progression of ovarian cancer. Participants will also receive standard cancer treatments, carboplatin and liposomal doxorubicin. The trial seeks women with ovarian cancer that has recurred but still responds to platinum-based treatments. Participants should not have previously used statin medications and must not have certain other health conditions, such as liver disease or uncontrolled illnesses. As an Early Phase 1 trial, this research aims to understand how simvastatin works in people, offering participants a chance to contribute to groundbreaking cancer treatment research.

Do I have to stop taking my current medications?

The trial requires that you do not use any statin medications or medications that interact with statins. If you are on such medications, you will need to stop them to participate.

Will I have to stop taking my current medications?

The trial requires that you do not currently use any statin medications or medications that interact with statins. If you are on such medications, you may need to stop them to participate.

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

Research shows that simvastatin, a type of medication known as a statin, is usually well-tolerated. Statins are commonly used to lower cholesterol levels. Some studies suggest that simvastatin might reduce the risk of ovarian cancer and help those with the disease live longer. These studies have not reported any major serious side effects specifically linked to simvastatin. However, as this is an early-stage trial, the main goal is to assess the safety and practicality of simvastatin for people with ovarian cancer. Ensuring safety remains a top priority in early-stage trials. ^{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 involve chemotherapy and targeted therapy, Simvastatin is unique because it is traditionally used to lower cholesterol. Researchers are excited about Simvastatin because it might offer a novel approach by targeting cancer cells' lipid metabolism, which is a different mechanism than current treatments. This potential to disrupt cancer cell growth through a new pathway is what makes Simvastatin particularly intriguing for ovarian cancer therapy.

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

Research has shown that simvastatin, which participants in this trial will receive, can inhibit the growth of ovarian cancer cells by halting their division. One study found that simvastatin induced stress in cancer cells and increased their death rate. Statins, including simvastatin, have been associated with a reduced risk of developing ovarian cancer. Additionally, studies have shown that using statins can help ovarian cancer patients live longer. The drug disrupts the pathways cancer cells use to grow and spread. These findings offer a hopeful outlook for using simvastatin in treating ovarian cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Bobbie Jo Rimel, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for women with recurrent ovarian cancer that responds to platinum-based chemotherapy, provided they haven't used statins or drugs that interact with them, have no liver disease or uncontrolled illnesses, and don't consume excessive alcohol.

Inclusion Criteria

My ovarian cancer has returned but responds to platinum treatment.

I am not allergic or unable to take carboplatin, liposomal doxorubicin, or simvastatin.

Exclusion Criteria

You drink more than 5 alcoholic drinks every day.

I do not have any unmanaged ongoing illnesses.

Current use of any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive simvastatin intervention alongside carboplatin and liposomal doxorubicin chemotherapy

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Simvastatin

Trial Overview

The study tests the use of Simvastatin 40mg in combination with carboplatin and liposomal doxorubicin on 20 patients at Cedars-Sinai Medical Center to see if it slows down cancer progression in those with platinum-sensitive ovarian cancer.

How Is the Trial Designed?

Group I: Simvastatin Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Bobbie Jo Rimel, MD

Lead Sponsor

Trials

1

Recruited

20+

Marc Goodman

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Simvastatin significantly inhibits ovarian cancer cell proliferation and induces cell cycle arrest and apoptosis, suggesting it has potential anti-tumor effects through mechanisms involving the mevalonate pathway and inhibition of key signaling pathways like MAPK and mTOR.

In an orthotopic mouse model, simvastatin reduced ovarian tumor growth and decreased markers of cell proliferation and survival, indicating its potential as a therapeutic option for ovarian cancer that warrants further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer. Stine, JE., Guo, H., Sheng, X., et al.[2022]

The combination of fluvastatin and cisplatin significantly inhibits the proliferation of ovarian cancer cells more effectively than either drug alone, indicating a synergistic effect in treating this type of cancer.

This combination therapy leads to cell cycle arrest and increased early apoptosis, while also disrupting the Ras signaling pathway, suggesting a potential new therapeutic role for statins in ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluvastatin and cisplatin demonstrate synergistic cytotoxicity in epithelial ovarian cancer cells. Taylor-Harding, B., Orsulic, S., Karlan, BY., et al.[2018]

In a retrospective study of 60 patients with advanced-stage ovarian cancer, statin use did not show any significant improvement in overall survival compared to those not using statins (P = 0.966).

The presence of residual tumor after treatment was significantly associated with better overall survival, indicating that tumor status is a more critical factor in patient outcomes than statin use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin as a Combined Therapy for Advanced-Stage Ovarian Cancer: A Propensity Score Matched Analysis. Chen, HY., Wang, Q., Xu, QH., et al.[2018]

Simvastatin significantly inhibited the proliferation of ovarian clear cell carcinoma (OCCC) cells by approximately 40% to 50% in vitro, indicating its potential as an effective treatment option.

In vivo studies using a xenograft tumor model showed that simvastatin not only inhibited tumor growth but also improved survival rates in treated mice compared to control groups, suggesting its promising anticancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma. Matsuura, M., Suzuki, T., Suzuki, M., et al.[2013]

Research is focusing on non-cross-resistant drugs like oxaliplatin and topotecan for treating drug-resistant ovarian cancer, with many being tested in combination therapies to improve outcomes.

Innovative strategies such as anticancer vaccines and gene therapy are being explored, highlighting the importance of clinical trials for women with advanced ovarian cancer due to low current cure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative therapies for advanced ovarian cancer. Trimble, EL.[2012]

The combination of simvastatin and irinotecan effectively suppresses the growth of colon cancer cells, even in those resistant to irinotecan, indicating a potential strategy to enhance treatment efficacy.

The optimal synergistic effect was observed at a 2:1 molar ratio of simvastatin to irinotecan, suggesting that this specific combination could be a promising approach for overcoming drug resistance in colon cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance. Jang, HJ., Hong, EM., Jang, J., et al.[2020]

In a phase II trial involving 60 patients with metastatic colorectal cancer, the addition of simvastatin to the XELOX and bevacizumab chemotherapy regimen resulted in a median progression-free survival of 10.4 months and a median overall survival of 19.0 months, indicating its efficacy as a first-line treatment.

The combination therapy achieved a high disease-control rate of 88.3% and an overall response rate of 58.3%, while maintaining a manageable safety profile, with only one patient experiencing significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients. Kim, Y., Kim, TW., Han, SW., et al.[2020]

Simvastatin effectively inhibits the mevalonate pathway in high-grade serous carcinoma (HGSC) cells, leading to reduced tumor growth and increased apoptosis, regardless of the p53 mutation status.

In a study using murine oviductal epithelial cells, simvastatin was found to be more effective than other statins in reducing cell proliferation and promoting tumor regression, suggesting its potential as a therapeutic option for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo. Pereira, M., Glogova, A., Haagsma, J., et al.[2023]

Ovarian cancer, which affects 6.6 per 100,000 women, may be linked to changes in lipid metabolism that cause inflammation, and patients often develop resistance to chemotherapy.

Statins, known for lowering cholesterol, show promise as a repurposed treatment for ovarian cancer due to their potential antitumor effects, and advancements in nanotechnology could enhance their effectiveness by improving drug delivery and bioavailability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin as Repurposed Drug in Ovarian Cancer: A Comprehensive Review. Ahmad, A., Javed, S., Kiran, S.[2023]

In a study of 442 patients with epithelial ovarian cancer, statin use did not show a significant overall benefit in progression-free survival (PFS) or disease-specific survival (DSS) compared to non-users.

However, among patients with non-serous-papillary ovarian cancer, statin use was linked to a significant reduction in the risk of disease recurrence and death, suggesting a potential targeted benefit for this specific subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin therapy is associated with improved survival in patients with non-serous-papillary epithelial ovarian cancer: a retrospective cohort analysis. Habis, M., Wroblewski, K., Bradaric, M., et al.[2021]

Polymeric nanoparticles made from Ecoflex® were successfully developed to deliver docetaxel (DTX) for ovarian cancer treatment, showing improved drug uptake and reduced side effects compared to free DTX.

In vivo studies on tumor-bearing mice demonstrated that DTX-loaded nanoparticles significantly enhanced anti-tumor efficacy, suggesting they could be a promising alternative to existing DTX formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by electrospraying technique for docetaxel delivery in ovarian cancer induced mice. Varshosaz, J., Ghassami, E., Noorbakhsh, A., et al.[2022]

Ovarian cancer is a leading cause of gynecological cancer deaths, with a low 5-year survival rate of 45%, highlighting the urgent need for new treatment options.

The presence of T cells in ovarian cancer tumors is linked to better survival outcomes, suggesting that immunotherapy, including cancer vaccines and adoptive T-cell therapy, could be a promising approach to improve treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opportunities in immunotherapy of ovarian cancer. Coukos, G., Tanyi, J., Kandalaft, LE.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9845598/

Advances in ovarian cancer treatment using a combination ...

The results demonstrated that all three statins could inhibit cell proliferation without causing cell apoptosis while also arresting the G1 and S phases.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7484024/

Systematic review and meta-analysis of studies assessing the ...

Statin use was associated with a reduced risk of ovarian cancer (RR 0.87, 95% CI: 0.74–1.03) and risk was significantly reduced in populations with low ...

3.

gynecologiconcology-online.net

gynecologiconcology-online.net/article/S0090-8258(14)00532-0/fulltext

The HMG-CoA reductase inhibitor simvastatin exhibits ...

Conclusions: Simvastatin potently inhibited ovarian cancer cell growth via G1 arrest, caused cellular stress, and increased apoptosis. These antitumorigenic ...

4.

erc.bioscientifica.com

erc.bioscientifica.com/view/journals/erc/25/10/ERC-18-0132.xml

Simvastatin interferes with cancer 'stem-cell' plasticity ...

Our laboratory and others showed that statins reduce cancer cell migration and induce cell death by inhibiting the mevalonate pathway and prenylation of small ...

5.

spandidos-publications.com

spandidos-publications.com/10.3892/ol.2022.13648

Statin use improves the prognosis of ovarian cancer

The results suggested that statin use markedly improved the OS in patients with OC, including in those with serous and endometrioid OC.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11098902/

Use of statins and risks of ovarian, uterine, and cervical diseases

Outcome. The outcomes were first diagnoses of ovarian cancer, endometrial cancer, cervical cancer, ovarian cyst, polycystic ovarian syndrome ...

7.

tandfonline.com

tandfonline.com/doi/full/10.1080/14737140.2024.2426551?src=

Full article: Statin use and ovarian cancer outcomes

They recounted that statin use was associated with a reduced risk (RR) of ovarian cancer (RR 0.87, 95% CI 0.74–1.03), an effect that was further pronounced with ...

8.

aacr.org

aacr.org/about-the-aacr/newsroom/news-releases/use-of-lipophilic-statins-is-associated-with-lower-mortality-from-ovarian-cancer/

Use of Lipophilic Statins is Associated with Lower Mortality ...

Use of any statins was associated with a 40 percent reduction in ovarian cancer mortality compared with patients who never used statins.