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

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm pilot trial to evaluate the feasibility of using a simvastatin intervention, and to evaluate its effects on cancer progression, among 20 patients with platinum-sensitive ovarian cancer, treated with carboplatin and liposomal doxorubicin at Cedars-Sinai Medical Center.

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.

What data supports the idea that Statin Therapy for Ovarian Cancer (also known as: Simvastatin, Zocor, Simvastatin) is an effective treatment?

The available research shows that simvastatin, a drug used in statin therapy, has promising effects in treating ovarian cancer. In studies, simvastatin was found to significantly slow down the growth of ovarian cancer cells and even cause them to die. It also reduced the ability of cancer cells to spread and stick to other areas. In experiments with mice, simvastatin treatment led to smaller tumor sizes and longer survival times. Additionally, in ovarian clear cell carcinoma, simvastatin reduced cell growth by about 40% to 50% and helped mice live longer. These findings suggest that simvastatin could be a beneficial treatment for ovarian cancer and deserves more research in clinical trials. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Simvastatin for ovarian cancer?

Research shows that Simvastatin, a drug commonly used to lower cholesterol, may also help fight ovarian cancer by stopping cancer cells from growing and spreading. In studies, it reduced tumor growth and increased survival in mice, suggesting it could be beneficial for treating ovarian cancer. ^{1 2 3 4 5}

What safety data exists for using statins in ovarian cancer treatment?

The review titled 'Statin as Repurposed Drug in Ovarian Cancer: A Comprehensive Review' suggests that statins, such as Simvastatin, have potential antitumor effects and could be repurposed for ovarian cancer treatment. The review discusses the pharmacotherapeutic potential of statins and highlights studies examining their impact on risk reduction and survival in ovarian cancer patients. It also mentions the use of nanotechnology to improve the drug's bioavailability and targeted delivery, which could enhance safety and efficacy. However, specific safety data for statins in ovarian cancer treatment is not detailed in the provided abstracts. ^{6 7 8 9 10}

Is statin therapy generally safe for humans?

Statins, like Simvastatin, are commonly used to lower cholesterol and have been studied for their safety in humans for various conditions. They are generally considered safe, but as with any medication, they can have side effects, so it's important to discuss with a doctor. ^{6 7 8 9 10}

Is the drug used in the trial 'Statin Therapy for Ovarian Cancer' a promising treatment?

Yes, the drug simvastatin shows promise as a treatment for ovarian cancer. It has been found to slow down cancer cell growth, cause cancer cells to die, and reduce tumor size in studies. This suggests it could be beneficial in treating ovarian cancer. ^{1 2 5 11 12}

How does statin therapy differ from other treatments for ovarian cancer?

Statin therapy, particularly using simvastatin, is unique for ovarian cancer as it targets the mevalonate pathway, which is involved in cancer cell growth and survival. Unlike traditional chemotherapy, simvastatin not only reduces cholesterol but also inhibits cancer cell proliferation, induces cell death, and reduces tumor growth, making it a novel approach in ovarian cancer treatment. ^{1 2 5 11 12}

Research Team

Bobbie Jo Rimel, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

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.

Current use of any other investigational agents

I do not have any unmanaged ongoing illnesses.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Simvastatin Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Bobbie Jo Rimel, MD

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer. [2022]

2. Greece pubmed.ncbi.nlm.nih.gov

Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma. [2013]

3. Korea (South) 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. [2020]

4. United States 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. [2021]

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

Fluvastatin and cisplatin demonstrate synergistic cytotoxicity in epithelial ovarian cancer cells. [2018]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Statin as Repurposed Drug in Ovarian Cancer: A Comprehensive Review. [2023]

7. Egypt pubmed.ncbi.nlm.nih.gov

Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance. [2020]

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

Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by electrospraying technique for docetaxel delivery in ovarian cancer induced mice. [2022]

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

Innovative therapies for advanced ovarian cancer. [2012]

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

Opportunities in immunotherapy of ovarian cancer. [2020]

11. England 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. [2023]

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

Statin as a Combined Therapy for Advanced-Stage Ovarian Cancer: A Propensity Score Matched Analysis. [2018]