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.
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.12345
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.678910
Is the drug used in the trial 'Statin Therapy for Ovarian Cancer' a promising treatment?
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.
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Treatment Details
Interventions
- Simvastatin (HMG-CoA Reductase Inhibitor)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: SimvastatinExperimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cedars Sinai Medical CenterLos Angeles, CA
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Who Is Running the Clinical Trial?
Bobbie Jo Rimel, MDLead Sponsor
References
The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer. [2022]Ovarian cancer is the 5th leading cause of cancer death among women in the United States. The mevalonate pathway is thought to be a potential oncogenic pathway in the pathogenesis of ovarian cancer. Simvastatin, a 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) inhibitor, is a widely used drug for inhibiting the synthesis of cholesterol and may also have anti-tumorigenic activity. Our goal was to evaluate the effects of simvastatin on ovarian cancer cell lines, primary cultures of ovarian cancer cells and in an orthotopic ovarian cancer mouse model. Simvastatin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, and caused cellular stress via reduction in the enzymatic activity of HMGCR and inhibition of the MAPK and mTOR pathways in ovarian cancer cells. Furthermore, simvastatin induced DNA damage and reduced cell adhesion and invasion. Simvastatin also exerted anti-proliferative effects on primary cell cultures of ovarian cancer. Treatment with simvastatin in an orthotopic mouse model reduced ovarian tumor growth, coincident with decreased Ki-67, HMGCR, phosphorylated-Akt and phosphorylated-p42/44 protein expression. Our findings demonstrate that simvastatin may have therapeutic benefit for ovarian cancer treatment and be worthy of further exploration in clinical trials.
Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma. [2013]Poor prognosis in ovarian clear cell carcinoma is associated with the expression of a defined set of proteins including osteopontin (OPN) and integrin. Statins, a family of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, are currently being investigated for the treatment and prevention of cancer. In this study, we investigated the effects of simvastatin on ovarian clear cell carcinoma (OCCC) cells in vitro and in vivo and elucidated the mechanism of drug action. Changes in OPN gene expression were determined by real-time RT-PCR, and an MTT assay was performed to determine effects on cell proliferation. Finally, a xenograft tumor model was constructed to evaluate the effects of simvastatin on cell proliferation and apoptosis in vivo. According to our experimental results, OPN is an important protein in OCCC. Simvastatin inhibited OCCC cell proliferation, and the inhibition rate was approximately 40% to 50% after treatment with 10 µM simvastatin for 48 h. In the xenograft studies, simvastatin treatment resulted in a significant growth inhibition. Furthermore, the mice treated with simvastatin survived significantly longer compared to the control groups. In conclusion, simvastatin has anticancer effects in vitro and in vivo. Further confirmation of the anticancer effects of statins in future studies will increase the scope for OCCC treatment.
A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients. [2020]Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC).
Statin therapy is associated with improved survival in patients with non-serous-papillary epithelial ovarian cancer: a retrospective cohort analysis. [2021]To determine whether statin use is associated with improved epithelial ovarian cancer (OvCa) survival.
Fluvastatin and cisplatin demonstrate synergistic cytotoxicity in epithelial ovarian cancer cells. [2018]Statin therapy has been associated with prolonged survival in patients with ovarian cancer. We hypothesized that statins have a cytotoxic effect and that the combination of fluvastatin and cisplatin inhibits cellular proliferation in epithelial ovarian cancer cells.
Statin as Repurposed Drug in Ovarian Cancer: A Comprehensive Review. [2023]With a prevalence rate of 6.6 per 100,000 women, ovarian cancer is the third most lethal gynecological tumor in the world. Several factors like family history, nulliparity, late menopause, genetic mutation, and an unhealthy lifestyle contribute to increasing the risk of ovarian cancer development. Novel research studies suggest that ovarian cancer may be caused by changes in the lipid metabolic profile that trigger inflammatory responses. Moreover, ovarian cancer patients will eventually experience chemoresistance. Statin, a competitive inhibitor of HMG-CoA reductase that is a lipid-lowering drug with pleiotropic effects, seems to be the best choice to deal with this therapeutic issue. The aim of this review is to highlight the pharmacotherapeutic potential of statins, especially the repurposing of statin drugs for antitumor mechanisms. This review will also provide a brief summary of the meta-analysis, and case-control observational studies carried out to examine the impact of statins on risk reduction and survival in ovarian cancer patients. Furthermore, this review will discuss the nanotechnological approach for improving the drug's bioavailability and safe and targeted delivery with controlled release of active ingredients, making statins more effective in preventing and treating ovarian cancer.
Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance. [2020]Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan. Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance. Results. The IC50 values of simvastatin alone and irinotecan alone were 115.4 ± 0.14 μM (r = 0.98) and 62.5 ± 0.18 μM (r = 0.98) in HT-29 cells without resistance to irinotecan. The IC50 values of these two drugs were 221.9 ± 0.22 μM (r = 0.98) and 195.9 ± 0.16 μM (r = 0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at 2 : 1 molar ratio showed the best synergistic interaction. Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer.
Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by electrospraying technique for docetaxel delivery in ovarian cancer induced mice. [2022]Ovarian cancer is still a major cause of morbidity and mortality. Docetaxel (DTX) is one of the most notable cytotoxic agents for treatment of ovarian cancer. However, its side effects proposed considerable problems to the patients.
Innovative therapies for advanced ovarian cancer. [2012]The emergence of drug-resistant tumors during therapy for ovarian cancer remains an obstacle to improving long-term outcomes. Active areas of ovarian cancer research include clinical evaluation of non-cross-resistant antineoplastic agents that demonstrated single-agent activity in ovarian cancer during the 1990s: oxaliplatin, the new anthracyclines (epirubicin, liposomal doxorubicin), topotecan, oral etoposide, gemcitabine, and vinorelbine. Most of these new agents are currently being evaluated as a component of doublet and triplet combination regimens for advanced ovarian cancer, with use of sequential alternating doublet regimens gaining interest. The potential role of intraperitoneal therapy continues to be investigated. In addition, there are a variety of innovative treatment strategies on the horizon that are targeted at underlying disease processes, including anticancer vaccines, gene therapy, and antiangiogenic therapy. Based on this multitude of investigational questions and the low cure rates currently achieved, all women with advanced ovarian cancer should be offered participation in clinical trials.
Opportunities in immunotherapy of ovarian cancer. [2020]Ovarian cancer (OC) is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival, the 5-year survival rates remain ominously low at 45%. Novel therapies are urgently needed. The presence of T cells in the OC tumor microenvironment is correlated with improved progression-free and overall survival, while the presence of regulatory T cells and expression of T-cell inhibitory molecules is correlated with a poor prognosis. These data indicate that immunotherapy could hold promise in improving the treatment of OC. In this review, we will discuss the rational of immunotherapy, highlight current results with cancer vaccines, adoptive T-cell therapy and immunomodulatory agents and summarize the immune effects of selected chemotherapeutic and radiotherapeutic agents.
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]High-grade serous carcinoma (HGSC) is the most common and aggressive subtype of epithelial ovarian cancer, characterized by gain-of-function TP53 mutations originating in the fallopian tube epithelium. Therapeutic intervention occurs at advanced metastatic disease, due to challenges in early-stage diagnosis, with common disease recurrence and therapy resistance despite initial therapy success. The mevalonate pathway is exploited by many cancers and is potently inhibited by statin drugs. Statins have shown anti-cancer activity in many, but not all cancers. Here, we investigated the role of p53 status in relation to mevalonate pathway signaling in murine oviductal epithelial (OVE) cells and identified OVE cell sensitivity to statin inhibition. We found that p53R175H mutant and Trp53 knockout OVE cells have increased mevalonate pathway signaling compared to p53 wild-type OVE cells. Through orthotopic implantation to replicate the fallopian tube origin of HGSC, p53R175H mutant cells upregulated the mevalonate pathway to drive progression to advanced-stage ovarian cancer, and simvastatin treatment abrogated this effect. Additionally, simvastatin was more efficacious at inhibiting cell metabolic activity in OVE cells than atorvastatin, rosuvastatin and pravastatin. In vitro, simvastatin demonstrated potent effects on cell proliferation, apoptosis, invasion and migration in OVE cells regardless of p53 status. In vivo, simvastatin induced ovarian cancer disease regression through decreased primary ovarian tumor weight and increased apoptosis. Simvastatin also significantly increased cytoplasmic localization of HMG-CoA reductase in ovarian tumors. Downstream of the mevalonate pathway, simvastatin had no effect on YAP or small GTPase activity. This study suggests that simvastatin can induce anti-tumor effects and could be an important inhibitor of ovarian cancer progression.
Statin as a Combined Therapy for Advanced-Stage Ovarian Cancer: A Propensity Score Matched Analysis. [2018]Background. Despite the great achievements in the treatment of advanced-stage ovarian cancer, it is still a severe condition with an unfavorable 5-year survival rate. Statins have been suggested to reduce the risk of several cancers beyond their cholesterol-lowing effects. However, the prognostic significance of statins in patients with advanced-stage ovarian cancer remains controversial. Methods. A retrospective study was performed to evaluate the association between statin intake and overall survival (OS) among patients with advanced-stage ovarian cancer. Patients who underwent cytoreductive surgery followed by courses of intravenous chemotherapy were matched through a propensity score analysis. Results. A total of 60 propensity-matched patients were included. Women in statin group showed a similar OS than the nonstatin counterparts (P = 0.966), whereas residual tumor was significantly associated with better OS (P = 0.013) and was an independent factor that associated with OS (P = 0.002, hazard ratio = 5.460, and 95% confidence interval: 1.894 to 15.742) in multivariable analysis. Conclusions. Our results suggested that statin usage was not associated with improved OS in patients with advanced-stage ovarian cancer undergoing surgery and chemotherapy. Considering the retrospective nature and the relative small sample size of the study, further prospective studies and random control trials are needed.