Targeting Immune Modulation in High Grade Serous Carcinoma: Combined Effects of Chemotherapy and Atorvastatin

Targeting Immune Modulation in High Grade Serous Carcinoma: Combined Effects of Chemotherapy and Atorvastatin

The goal of this clinical trial is to learn how atorvastatin in patients with advanced high grade serous cancer of the ovary, fallopian tube, or peritoneum changes the tumor immune environment. The main question it aims to answer is:

• Does atorvastatin combined with standard of care chemotherapy and surgery changes the number of tumor-promoting macrophages in the tumor microenvironment
• Researchers will compare standard of care chemotherapy and surgery to see if there is a difference in tumor promoting macrophages.
• Participants will take atorvastatin (daily pill) alongside their standard treatment.

Inclusion Criteria:

• Be a patient with ovarian cancer aged 18-89
• Diagnosed via tissue biopsy not ascites
• For persons of reproductive potential, use of highly effective method(s) of contraception.
• Patients with primary Stage III/IV high-grade serous ovarian/fallopian tube/primary peritoneal cancer not amenable to upfront cytoreductive surgery.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
• Absolute Neutrophil Count 1500 cells/mL
• Platelet count > 100,000 mL.
• Hemoglobin 9.0 g/dL
• Serum albumin ³ 2.5 g/dL.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
• aspartate aminotransferase (AST )and alanine aminotransferase (ALT) ≤ 3.0 x ULN.
• Serum creatinine ≤ 1.5x ULN

Exclusion Criteria:

• Inability to comply with study and follow-up procedures.

• Significant cardiovascular disease, such as New York Heart Association cardiac disease (class II or greater), myocardial infarction within the past 3 months, unstable arrhythmia, or unstable angina.

• Known clinically significant liver disease defined as AST and ALT > 3.0 x ULN and/or total bilirubin ≥ 1.5 x ULN, or documented history of active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease.

• Participation in investigational clinical trial within last 30 days.

• Medical history of untreated HIV infection. Patients with medical history of HIV infection are eligible provided they meet following criteria

  • Are stable on antiretroviral therapy for ≥4 weeks before randomization
  • Agree to adhere to antiretroviral therapy per World Health Organization (WHO) guidelines
  • Have no documented multi-drug resistance that would prevent effective antiretroviral therapy
  • Have a viral load of <400 copies per mL at screening
  • Have CD4+ T cell count at ≥ 350 cells per μL
  • Have no history of acquired immunodeficiency syndrome (AIDS) -defining opportunistic infection ≤ 12 months before randomization.

• Inability to provide informed consent.

• Known central nervous system (CNS) malignancy or CNS metastases.

• Patients with previous malignancy within the past 2 years from cycle 1, day 1, except those with negligible risk of metastasis or death, such as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the breast.

• History of stroke or transient ischemic attack (TIA) within 3 months prior to cycle 1 day 1(C1D1).

• Patients with prognosis for survival less than 6 months.

• Patients deemed otherwise clinically unfit for clinical trial per Investigator's discretion.

• Patients with duodenal stent or other gastrointestinal (GI) disorder/defect that would interfere with absorption of oral medication.

  o Includes patients unable to swallow orally administered medication and patients with GI disorders likely to interfere with absorption of the study medication

• Female patients who maintain fertility potential and refuse to comply to use contraception and be followed for pregnancy by pregnancy testing.

• Patients who are currently pregnant or lactating.

• Prior or current statin use that would prohibit randomization into SOC arm.

• Planned treatment with bevacizumab in the primary treatment setting.

• Diagnosis based on ascites assessment only and not a tissue biopsy.

• Patients deemed otherwise clinically unfit for clinical trial per investigators discretion