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.

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Chemotherapy

Pembrolizumab + Chemotherapy Before Surgery for Bladder Cancer

Phase 2

Waitlist Available

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

No Placebo-Only Group

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

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My bladder cancer is mainly not urothelial type.

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I agree to have surgery aimed at curing my condition.

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My kidney function tests are within the required range.

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

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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:

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

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

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I have been treated with specific immune therapy drugs before.

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

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I have an active hepatitis B or C infection.

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I have a known history of HIV.

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I have received an organ transplant from another person.

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My cancer does not have pure small cell characteristics.

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I am currently being treated for an infection.

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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.

Secondary study objectives

Incidence of adverse events

Recurrence-free survival

Tumor infiltrating lymphocyte (TIL) density

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

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: 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

Cisplatin

2013

Completed Phase 3

~3120

Radical Cystectomy

2006

Completed Phase 2

~140

Doxorubicin

2012

Completed Phase 3

~8030

Methotrexate

2019

Completed Phase 4

~4400

Pegfilgrastim

2013

Completed Phase 3

~4440

Pembrolizumab

2017

Completed Phase 3

~3130

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.