Rivaroxaban for Urinary Tract Cancer

(PREVENT-GU Trial)

Overseen By David J Yachnin, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Anticoagulants, Dual antiplatelets

Disqualifiers: Severe renal insufficiency, Severe liver disease, Thrombocytopenia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with genitourinary cancers (ex: bladder, testicular, kidney) are at high risk of developing blood clots if they receive systemic therapy (ex: chemotherapy, immunotherapy). Blood clots cause pain, may require hospitalization and invasive testing, and in some cases cause death. In fact, blood clots are one of the leading causes of death in patients with cancer. Furthermore, patients who develop a blood clot require medication to thin the blood for a prolonged (sometimes indefinite) period of time, and this can disrupt other important cancer treatments. Studies have shown that using low dose blood thinners to prevent blood clots during systemic therapy is effective in some patients with cancer. However very few patients in these studies had genitourinary cancers, therefore physicians in Canada are not sure if recommending blood thinners to patients with genitourinary cancers is useful or safe. Safety is a primary concern because blood thinners may cause bleeding, and patients with genitourinary cancers may have higher risk of bleeding than patients with other types of cancer. The investigators hypothesize that blood thinners are effective and safe for reducing blood clots in patients with genitourinary cancers. The objective of this study is to determine if a large clinical trial testing the effectiveness and safety of low dose blood thinners for preventing blood clots in patients with genitourinary cancers receiving systemic therapy is feasible.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain blood thinners, dual antiplatelet therapy, or medications that strongly interact with rivaroxaban. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Rivaroxaban for treating urinary tract cancer?

Rivaroxaban has been shown to be effective in preventing blood clots in cancer patients, as seen in studies where it was compared to other blood thinners like enoxaparin. While this doesn't directly show its effectiveness for urinary tract cancer, it suggests Rivaroxaban can be beneficial in managing blood clot risks in cancer patients. ^{1 2 3 4 5}

Research Team

Luke T Lavallee, MDCM MSc FRCSC

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for adults over 18 with genitourinary cancers (like bladder or kidney cancer) except prostate cancer, who are starting systemic treatments like chemotherapy. They must be planning to undergo treatment for at least 8 weeks.

Inclusion Criteria

I am eligible for treatments like chemotherapy, targeted therapies, and immunotherapies.

I am starting a treatment that will last at least 8 weeks.

I am starting treatment for a urinary cancer, but not prostate cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Rivaroxaban or placebo during systemic therapy for genitourinary cancers

26 weeks

Regular visits for monitoring and pill counts

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue to be monitored for long-term outcomes such as overall survival and quality of life

Long-term

Treatment Details

Interventions

• Rivaroxaban

Trial Overview The study tests if a low dose of Rivaroxaban, a blood thinner, can safely prevent blood clots in patients receiving systemic therapy for genitourinary cancers compared to a placebo control.

Participant Groups

Group I: Rivaroxaban Experimental Treatment 1 Intervention

Participants receiving study drug (Rivaroxaban)

Group II: Control Placebo Group 1 Intervention

Participants receiving matched placebo

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Kidney Cancer Research Network of Canada

Collaborator

Trials

1

Recruited

120+

Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network

Collaborator

Trials

12

Recruited

17,500+

Findings from Research

In patients with active cancer and venous thromboembolism, rivaroxaban was found to be as effective as enoxaparin followed by vitamin K antagonists in preventing recurrent venous thromboembolism, with a recurrence rate of 5% for rivaroxaban compared to 7% for standard therapy.

Rivaroxaban also demonstrated a significant reduction in major bleeding events (2% vs 5% for standard therapy), suggesting it may be a safer option for this patient group, although there was no significant difference in clinically relevant bleeding between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Prins, MH., Lensing, AW., Brighton, TA., et al.[2022]

In a study of 374 patients who underwent robot-assisted radical cystectomy, both oral apixaban and injectable enoxaparin were found to be equally effective in preventing venous thromboembolism (VTE), with VTE rates of 1.6% for apixaban and 3.2% for enoxaparin, showing no statistically significant difference (P = 0.5).

Apixaban was demonstrated to be a safe option for VTE prophylaxis after surgery, with no significant differences in major bleeding, complications, readmission, or mortality rates compared to enoxaparin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes from a prospectively implemented protocol using apixaban after robot-assisted radical cystectomy. Rich, JM., Elkun, Y., Geduldig, J., et al.[2023]

In a study of 657 patients who underwent radical cystectomy, the use of direct oral anticoagulants (DOAs) like apixaban and rivaroxaban showed a promising safety and efficacy profile for preventing venous thromboembolism (VTE), with no VTE events reported in the DOA group compared to 3.6% in the enoxaparin group.

Both DOAs and enoxaparin demonstrated similar effectiveness in reducing VTE risk, suggesting that DOAs can be a viable alternative to traditional enoxaparin therapy for extended prophylaxis after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Anticoagulation after Radical Cystectomy Using Direct Acting Oral Anticoagulants: A Single-Institutional Experience. Faraj, KS., Durant, A., Mauler, D., et al.[2023]

A clinical case highlighted the challenges of managing a patient with critical haematuria after prostate biopsies while on the oral anticoagulant Rivaroxaban, indicating a need for better protocols in perioperative care.

The case emphasized difficulties in monitoring and treating the haematuria due to the absence of biological control measures and an antidote for Rivaroxaban, suggesting potential safety concerns in its use during surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Critical haematuria after prostate biopsies with RIVAROXABAN. Case report]. Olivier, J., Yakoubi, R., Gras, S., et al.[2015]

The phase III RANGE study suggests that combining ramucirumab with docetaxel can enhance progression-free survival in patients with advanced or metastatic urothelial carcinoma who have not responded to platinum chemotherapy.

This finding indicates a potential new treatment strategy for a challenging patient population, improving outcomes for those with refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Angiogenesis in Bladder Cancer. [2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Outcomes from a prospectively implemented protocol using apixaban after robot-assisted radical cystectomy. [2023]

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

Extended Anticoagulation after Radical Cystectomy Using Direct Acting Oral Anticoagulants: A Single-Institutional Experience. [2023]

4. France pubmed.ncbi.nlm.nih.gov

[Critical haematuria after prostate biopsies with RIVAROXABAN. Case report]. [2015]

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

Targeting Angiogenesis in Bladder Cancer. [2019]