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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a low dose of rivaroxaban, a blood thinner, can safely and effectively prevent blood clots in individuals with certain urinary tract cancers, such as bladder or kidney cancer, who are undergoing treatments like chemotherapy or immunotherapy. Blood clots pose a significant risk because they can lead to serious health issues, including death, and may disrupt cancer treatment. The trial will compare rivaroxaban with a placebo (a harmless pill with no active drug) to determine its effectiveness. This study is ideal for those about to begin systemic therapy for their genitourinary cancer and who do not have other conditions requiring blood thinners. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

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.

Is there any evidence suggesting that Rivaroxaban is likely to be safe for humans?

Research has shown that rivaroxaban, a blood-thinning medication, is generally well-tolerated by cancer patients. Studies have found that it lowers the risk of blood clots but does not reduce hospital visits due to bleeding or affect overall survival rates. Some research suggests that rivaroxaban might cause more bleeding in patients with certain cancers, though this was not observed in those with lung cancer.

Safety is particularly crucial for patients with cancers of the urinary or reproductive systems, as they may have a higher risk of bleeding. Despite this, rivaroxaban is commonly used for cancer-related blood clots, indicating it is safe enough for further testing in clinical trials. Patients should always consult their healthcare provider to understand the risks and benefits for their specific situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Rivaroxaban for urinary tract cancer because it offers a novel approach compared to standard treatments like surgery, chemotherapy, or immunotherapy. Unlike these traditional options, Rivaroxaban is an anticoagulant that potentially targets the cancer's blood supply, which might help inhibit tumor growth. This unique mechanism of action could provide a new pathway for treating urinary tract cancer, sparking interest in its potential effectiveness and safety in cancer management.

What evidence suggests that Rivaroxaban might be an effective treatment for preventing blood clots in patients with genitourinary cancers?

Research shows that rivaroxaban can lower the risk of blood clots in cancer patients. One study found it reduced the chance of blood clots returning by 31% compared to LMWH, a common treatment. While rivaroxaban did not increase bleeding in lung cancer patients, it did in those with gastrointestinal cancer, suggesting that bleeding risk may depend on cancer type. This trial will assess rivaroxaban's effectiveness in patients with urinary tract cancer. Although data on its use in genitourinary cancers is limited, rivaroxaban's ability to prevent clots might also reduce clot risks in these patients during treatment. ^{1 2 3 6 7}

Who Is on the Research Team?

Luke T Lavallee, MDCM MSc FRCSC

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. e-juo.org e-juo.org/journal/view.php?number=436

A Study on the Efficacy and Safety of Rivaroxaban ... In these studies, rivaroxaban was associated with higher incidence of bleeding in treatment of gastrointestinal cancer, but not in lung cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11858610/

Comparison of Clinical Outcomes in Patients with Active ... Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes.

3. jacc.org jacc.org/doi/10.1016/j.jaccao.2022.10.014

Effectiveness and Safety of Rivaroxaban and Low ... At 3 months, rivaroxaban was associated with a 31% reduced risk of recurrent VTE vs LMWH (4.2% vs 6.1%; HR: 0.69; 95% CI: 0.51-0.92). No difference in bleeding- ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S247503792201617X

Rivaroxaban treatment of cancer‐associated venous ... From January 2014 through September 2016, 1072 patients began rivaroxaban treatment for CAT; 91.9% had a solid tumor, 8.1% had hematologic malignancies, and 75% ...

5. ashpublications.org ashpublications.org/bloodadvances/article/4/17/4045/463467/Effectiveness-and-safety-of-rivaroxaban-compared

Effectiveness and safety of rivaroxaban compared with low ... Rivaroxaban may be a reasonable alternative to LMWH for patients with CAT without gastrointestinal or genitourinary cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05920343

VTE Prevention With Rivaroxaban in Genitourinary Cancer ... Prior studies have reported VTE rates during chemotherapy for bladder and testis cancer in the range of 10-15%, well above thresholds at which guidelines ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1814630

Rivaroxaban for Thromboprophylaxis in High-Risk ... In high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous ...