What side effects are associated with this type of intervention?

Common treatments for bladder cancer, such as Pembrolizumab (PD-1 inhibition) and Cabozantinib (tyrosine kinase inhibition), have distinct side effect profiles. Pembrolizumab is associated with immune-related adverse events including skin reactions, endocrine disturbances, and severe neurological toxicities. Cabozantinib can cause diarrhea, fatigue, hypertension, and hand-foot syndrome. Both treatments carry the risk of serious adverse events that may require discontinuation.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA for the treatment of advanced urothelial carcinoma, particularly in patients who are ineligible for cisplatin-based chemotherapy or have disease progression after platinum-containing chemotherapy. Other PD-1/PD-L1 inhibitors approved for bladder cancer include nivolumab and atezolizumab. Cabozantinib, a tyrosine kinase inhibitor, is being studied in combination with pembrolizumab for its potential efficacy in treating advanced urothelial carcinoma, although it has not yet received FDA approval specifically for bladder cancer.

What other types of research exist?

Promising alternatives to Pembrolizumab and Cabozantinib for bladder cancer patients include Atezolizumab, another PD-L1 inhibitor, which is used for patients not responding to cisplatin-based chemotherapy and as a first-line treatment for cisplatin-ineligible patients. Additionally, Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, has shown efficacy in patients who have progressed after platinum-based chemotherapy and checkpoint inhibitors. Sacituzumab Govitecan, another antibody-drug conjugate, is also being investigated for its effectiveness in metastatic urothelial carcinoma after prior treatments.

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Tyrosine Kinase Inhibitor

Cabozantinib + Pembrolizumab for Bladder Cancer (PemCab Trial)

Phase 2

Waitlist Available

Research Sponsored by University of Utah

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

- Be greater to or equal to 18 years of age on day of signing informed consent

- Performance Status ECOG 0-2

Must not have

Has received prior treatment with cabozantinib

Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or other checkpoint inhibitors previously

Timeline

Screening 3 weeks

Treatment Varies

Follow Up patients are expected to stay on treatment for approximately 12 months; 18 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, pembrolizumab and cabozantinib, in patients with advanced bladder cancer who cannot take cisplatin. Pembrolizumab helps the immune system fight cancer, while cabozantinib stops cancer cells from growing. The study aims to see how well these drugs work together in improving patient outcomes.

Who is the study for?

Adults with advanced urothelial carcinoma who can't have cisplatin. They need a certain level of physical fitness (ECOG 0-2), adequate organ function, and no recent significant illnesses or treatments that could affect their participation. Participants must not be pregnant, agree to use effective contraception, and have recovered from any previous therapies' side effects.

What is being tested?

The trial is testing the combination of two drugs: Pembrolizumab and Cabozantinib in patients with metastatic urothelial carcinoma ineligible for cisplatin. It's an open-label phase 2 study focusing on how well tumors respond to treatment, how long patients live without disease progression at six months, and overall survival rates.

What are the potential side effects?

Possible side effects include fatigue, high blood pressure, hand-foot syndrome (redness and pain in hands/feet), mouth sores, loss of appetite, diarrhea or constipation. There may also be risks related to immune system reactions like inflammation in organs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I can take care of myself and am up and about more than 50% of my waking hours.

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My kidney function, measured by creatinine clearance, is low but not extremely poor.

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I have chosen not to participate in certain treatments.

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My cancer is confirmed to be urothelial carcinoma.

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I am eligible for a bladder tissue biopsy.

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I cannot receive any platinum-based chemotherapy treatments.

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My cancer has spread beyond its original site and cannot be surgically removed.

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I need some help with my daily activities.

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My nerve damage is mild or I don't have any.

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I have hearing loss.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with cabozantinib before.

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I have been treated with drugs targeting PD-1, PD-L1, or PD-L2 before.

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I have had chemotherapy for bladder cancer that has spread.

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I am taking blood thinners not listed in the exclusions.

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I haven't had major surgery in the last 2 months or minor surgery in the last 10 days.

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My heart's electrical activity, measured by ECG, is within normal limits.

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I have had an organ or stem-cell transplant.

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I am not on high dose steroids for an autoimmune disease.

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I have or had lung inflammation treated with steroids.

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I have been diagnosed with HIV.

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I am currently on IV antibiotics for an infection.

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I have a history of active tuberculosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ patients are expected to stay on treatment for approximately 12 months; 18 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~patients are expected to stay on treatment for approximately 12 months; 18 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and patients are expected to stay on treatment for approximately 12 months; 18 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Response Rate (ORR)

Secondary study objectives

Occurrence of Adverse Events and Serious Adverse Events

Overall Survival (OS)

Progression-free survival (PFS) at 6 months (PFS6)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Cabozantinib and Pembrolizumab, all patientsExperimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~2810

Cabozantinib

2020

Completed Phase 2

~1760

0 / 23Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Pembrolizumab, a PD-1 inhibitor, enhances the immune system's ability to detect and destroy cancer cells by blocking the PD-1 pathway, which cancer cells use to evade immune detection. Cabozantinib, a tyrosine kinase inhibitor, targets multiple pathways involved in tumor growth and blood vessel formation, thereby inhibiting tumor proliferation and reducing its blood supply. These mechanisms are significant for bladder cancer patients as they offer targeted approaches to control disease progression and improve survival rates.

[The role of immunotherapy in the modern treatment of urothelial carcinoma].