Statins to Prevent Cancer Associated Blood Clots

This trial is a randomized, double-blind, placebo-controlled trial of rosuvastatin 20 mg po daily in the prevention of venous thromboembolism (VTE) and other cardiovascular events among individuals recently diagnosed with cancer who are not scheduled to receive prophylactic anticoagulation and are at risk for VTE as defined by a Khorana Score (KS) 2 to 4 or a modified Khorana Score (mKS) 2 to 5.

• Rosuvastatin (Drug): Rosuvastatin is a statin drug that helps reduce cholesterol and can help reduce risks of blood clots. In this study, patients will take 20mg of Rosuvastatin (or placebo) for to 12 months.
• Placebo Drug (Drug): The placebo pills are pills with no medicine in them.

Primary outcomes

• Assess whether Rosuvastatin versus placebo over a period of one year reduces the risk of incident (first event) VTE among patients with cancer [12 months]: The primary endpoint of the trial is the time from taking the first dose of study medication after randomization (modified intention to treat, mITT) to the first confirmed occurrence of the primary VTE endpoint. The primary analysis will use a likelihood ratio test based on a proportional hazards model stratified by eligibility criteria (eligible due to KS criteria alone or eligible due to mKS criteria), and enrollng center to test the null hypothesis of no association between assignment to active statin treatment and the rate of the primary endpoint. All analyses will classify patients according to their randomized treatment assignment, i.e. according to the intention to treat principle, and will base evaluation of statistical significance on a two-sided test with level 0.05. The estimated relative hazard in the statin compared to the placebo group with accompanying 95% confidence interval will quantify the treatment effect45. If this relative hazard is less than 1, then 100*(1-esti

Secondary outcomes

• Assess whether Rosuvastatin versus placebo over a period of one year reduces the cumulative incidence of a composite of venous and arterial thrombosis events among patients with cancer [12 months]

Other outcomes

• Safety Endpoint: Identify transaminitis > 5 x ULN on two consecutive tests at least one week apart [12 months]
• Safety Endpoint: Identify CK > 5 x ULN on two consecutive tests at least one week apart [12 months]
• Safety Endpoint: Identify clinical myositis, rhabdomyolysis, major bleeding and clinically relevant non-major bleeding [12 months]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* age > 18 years with no contraindication to statin therapy and able to provide informed consent
* newly diagnosed, newly recurrent or newly progressive malignancy with locally advanced/metastatic disease initiating new systemic cancer therapy with no plan for prophylactic anticoagulation.
* intermediate or high risk for cancer associated VTE based on the Khorana Score (KS) and modified Khorana Score (mKS) risk assessment tools (KS 2-4 or mKS 2-5).
* ECOG performance status 0-2
* Life expectancy > 6 months

Exclusion Criteria:

* current use of statin therapy or known statin intolerance.
* current use of systemic anticoagulation.
* very low VTE risk defined by a Khorana Score (KS) of 0-1 and a modified Khorana Score (mKS) of 0-1.
* extremely high VTE risk defined by a Khorana Score (KS) > 5 or modified Khorana Score (mKS) > 6 where guideline recommendations for systemic anticoagulation should be considered.
* Basal cell or squamous cell carcinoma in situ cancers of the skin as the sole qualifying cancer type
* ineligible cancer types where level of acuity is likely to preclude trial participation (including acute leukemia, myelodysplastic syndromes, primary brain tumors, primary CNS lymphoma, or plans to undergo hematopoietic stem cell transplantation or CAR-T cell therapy). (g) Known ALT, AST, or creatine kinase (CK) levels > 3 x ULN; eGFR < 30 ml/min/1.73m2, or Child Pugh Class B or C liver disease
* Known hepatitis C or HIV disease, or intent to use certain oncologic agents (daralutemide, regorafenib, and cabozantinib) or some antivirals used to treat hepatitis C or HIV disease (combinations of sofosbuvir, velpatasvir, and voxilaprevir) which can significantly increase rosuvastatin exposure and potentially lead to drug-drug interactions (DDIs).
* Conditions that, in the opinion of the investigator, would compromise the well-being of the subject or conduct of the study, including as examples life expectancy less than 6 months or an ECOG Performance Status > 3.

NIH grants: UG3HL176627