What side effects are associated with this type of intervention?

The most common treatments for bladder cancer, such as immunotherapy with pembrolizumab and combination chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin, have distinct side effect profiles. Pembrolizumab, an immune checkpoint inhibitor, can cause immune-related adverse events including fatigue, rash, diarrhea, and more severe conditions like pneumonitis, colitis, and hepatitis. Combination chemotherapy often leads to side effects such as nausea, vomiting, hair loss, neutropenia (low white blood cell count), and increased risk of infections. Specific agents like cisplatin can cause nephrotoxicity (kidney damage) and ototoxicity (hearing loss), while adriamycin is known for its potential cardiotoxicity (heart damage). These side effects highlight the importance of close monitoring and supportive care during treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for bladder cancer, including immunotherapy and combination chemotherapy. Pembrolizumab, an immunotherapy drug, has been approved for use in patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. Other immunotherapy drugs like atezolizumab and nivolumab have also received FDA approval for similar indications. In terms of combination chemotherapy, regimens such as MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) have been used for advanced bladder cancer, although newer combinations and targeted therapies are continually being explored.

What other types of research exist?

Promising novel alternatives for bladder cancer treatment include Atezolizumab and Enfortumab Vedotin. Atezolizumab, an anti-PD-L1 monoclonal antibody, has shown efficacy in patients ineligible for cisplatin-containing chemotherapy. Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, has demonstrated effectiveness in patients who have progressed after platinum-based chemotherapy and PD-1/PD-L1 inhibitors.

← Back to Search

Chemotherapy

Pembrolizumab + Chemotherapy Before Surgery for Bladder Cancer

Phase 2

Recruiting

Led By Petros Grivas

Research Sponsored by University of Washington

Eligibility Criteria Checklist

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

Must have

Histology must be either pure or predominant non-urothelial histology (noted on any TURBT)

Patients must agree to undergo curative intent surgery

Must not have

Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing > 10 mg daily of prednisone dose equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug

Has history of (non-infectious) pneumonitis that required steroids or has current pneumonitis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 2 years

Awards & highlights

Summary

This trial is testing a mix of a drug that helps the immune system and another that targets cancer cells before surgery for a specific type of bladder cancer. It focuses on patients who may not respond well to usual treatments. The treatment helps the body fight cancer and uses drugs to kill or stop cancer cells.

Who is the study for?

This trial is for adults with muscle-invasive bladder cancer that looks unusual under the microscope and hasn't spread elsewhere. They must be fit for chemotherapy, surgery to remove the bladder, and willing to provide tissue samples. Participants need functioning major organs, no severe allergies to pembrolizumab or its components, no active hepatitis B/C or HIV, not pregnant or breastfeeding, and agree to use contraception.

What is being tested?

The study tests if combining pembrolizumab (an immune system-boosting drug) with chemotherapy drugs (methotrexate, vinblastine sulfate, doxorubicin hydrochloride, cisplatin) before surgery can better treat patients compared to chemotherapy alone. The goal is to see if this combination helps shrink the cancer more effectively before removing the bladder.

What are the potential side effects?

Possible side effects include reactions related to boosting the immune system which might affect different body parts like lungs or intestines; typical chemo-related issues such as nausea, hair loss; fatigue; increased risk of infections due to low blood cell counts; potential damage to kidneys from cisplatin.

Eligibility Criteria

Inclusion Criteria

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

Select...

My bladder cancer is mainly not urothelial type.

Select...

I agree to have surgery aimed at curing my condition.

Select...

My kidney function tests are within the required range.

Select...

I am considered fit for specific bladder cancer treatments by my doctors.

Select...

I haven't had a blood transfusion or taken erythropoietin in the last 2 weeks.

Exclusion Criteria

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

Select...

I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

Select...

I have had or currently have lung inflammation treated with steroids.

Select...

I have been treated with specific immune therapy drugs before.

Select...

I have not received a live vaccine in the last 30 days.

Select...

I have an active hepatitis B or C infection.

Select...

I have a known history of HIV.

Select...

I have received an organ transplant from another person.

Select...

My cancer does not have pure small cell characteristics.

Select...

I am currently being treated for an infection.

Select...

I have a known history of active tuberculosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Pathologic complete response rate

Secondary study objectives

Incidence of adverse events

Recurrence-free survival

Tumor infiltrating lymphocyte (TIL) density

Side effects data

From 2024 Phase 2 trial • 57 Patients • NCT03004183

21%

Fatigue

13%

Nausea

11%

Back pain

Diarrhea

Anemia

Shortness of Breath

Abdominal pain

Kidney Injury and/or Infection

Pneumonia

Weight Loss

Dyspnea

Malnutrition, Hypercalcemia and Weakness

Pneumothorax

Intractable pain, back pain, hip pain

Activated partial thromboplastin time prolonged

Atrial fibrillation with rapid ventricular response

Pleural effusion

colitis

Thrombocytopenia

Respiratory failure

Skin rash

100%

80%

60%

40%

20%

Study treatment Arm

Single Arm

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (pembrolizumab, aMVAC)Experimental Treatment7 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1 of weeks 0, 3, and 6 and methotrexate IV, vinblastine IV, doxorubicin IV, and cisplatin IV on day 1 of weeks 0, 2, 4, and 6 in the absence of disease progression or unacceptable toxicity. Patients also receive pegfilgrastim SC on day 1 or 2 of weeks 0, 2, 4, and 6 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care radical cystectomy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Radical Cystectomy

2006

Completed Phase 2

~140

Cisplatin

2013

Completed Phase 3

~1940

Doxorubicin

2012

Completed Phase 3

~7940

Methotrexate

2013

Completed Phase 4

~3800

Pegfilgrastim

2013

Completed Phase 3

~4440

Pembrolizumab

2017

Completed Phase 2

~2010

Vinblastine Sulfate

2007

Completed Phase 4

~300

0 / 15Eligibility 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

Bladder cancer treatments often include immunotherapy and combination chemotherapy. Immunotherapy, such as pembrolizumab, uses monoclonal antibodies to enhance the body's immune response against cancer cells by targeting proteins like PD-1, which helps the immune system recognize and attack tumor cells. This is crucial for patients as it can lead to more effective and sustained cancer control. Combination chemotherapy, involving drugs like methotrexate, vinblastine, adriamycin, and cisplatin, works by killing or inhibiting the growth and spread of cancer cells through various mechanisms, such as interfering with DNA replication and cell division. This approach is vital for reducing tumor size and preventing metastasis, thereby improving patient outcomes.