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Anti-metabolites

Pembrolizumab + Gemcitabine for Bladder Cancer

Phase 2

Recruiting

Led By Michael E Woods

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

All patients must have had a cystoscopy or transurethral resection of bladder tumor (TURBT) with complete resection without papillary tumor and negative urinary cytology within 28 days of registration

Patients with HIV must be on effective anti-retroviral therapy with undetectable viral load within 6 months of registration

Must not have

Known history of hepatitis B or known active hepatitis C virus infection

Known active CNS metastases and/or carcinomatous meningitis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years post treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether adding the immunotherapy drug pembrolizumab to the chemotherapy drug gemcitabine can help to treat patients with bladder cancer that has not responded to treatment with Bacillus Calmette-Guerin (BCG).

Who is the study for?

This trial is for adults with high-grade non-muscle invasive bladder cancer that hasn't responded to BCG treatment. Candidates must have had all visible tumors removed, not be pregnant or breastfeeding, agree to birth control use, and have proper organ function. Those unfit for radical cystectomy or refusing it can join. People with certain infections, recent radiation therapy to the lungs, active autoimmune diseases, other cancers within three years, or previous treatments with similar drugs are excluded.

What is being tested?

The study is testing if adding pembrolizumab (an immunotherapy drug) to gemcitabine (a chemotherapy drug) improves outcomes in patients whose bladder cancer has not improved after BCG treatment. Pembrolizumab helps the immune system fight cancer while gemcitabine works by killing or stopping tumor cells from growing.

What are the potential side effects?

Pembrolizumab may cause immune-related side effects like inflammation of organs and infusion reactions; fatigue; skin rash; digestive issues such as nausea and diarrhea; liver problems; hormonal gland problems leading to hormone deficiencies. Gemcitabine can cause blood disorders, flu-like symptoms, swelling at the injection site and hair loss.

Eligibility Criteria

Inclusion Criteria

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

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I've had a complete bladder tumor removal and tests show no cancer cells in my urine.

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I have HIV, am on treatment, and my viral load has been undetectable for the last 6 months.

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My condition did not improve after initial and follow-up bladder cancer treatments.

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My bladder cancer is high risk and hasn't improved 9 months after BCG treatment.

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I cannot undergo or refuse to have major bladder surgery as advised by my doctor.

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My bladder cancer is high grade and not deeply invasive.

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I am 18 years old or older.

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I was cancer-free 6 months after starting BCG but it came back during maintenance.

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I am not pregnant and have a negative pregnancy test taken within the last week.

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I am able to care for myself and perform daily activities.

Exclusion Criteria

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

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I have a history of hepatitis B or an active hepatitis C infection.

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I have active brain metastases or cancer in the lining of my brain.

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I had a stem cell transplant from a donor within the last 5 years.

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I have had idiopathic pulmonary fibrosis or organizing pneumonia.

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I have had pneumonitis treated with steroids or have it now.

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I am currently on medication for an infection.

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I have been treated with specific immune therapy drugs before.

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I have not had radiotherapy in the last 2 weeks.

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I have not received any live vaccines in the last 30 days.

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My cancer is of mixed type, not purely one type.

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I have another cancer that has worsened or needed treatment in the last 3 years.

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I am HIV-positive and have had Kaposi sarcoma or multicentric Castleman disease.

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I have active tuberculosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years post treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years post treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years post treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Complete response rate in the carcinoma in situ (CIS) subpopulation

Event-free survival at 18 months

Secondary study objectives

Cystectomy-free survival

Duration of response (DOR)

Incidence of adverse events

+3 more

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, gemcitabine hydrochloride)Experimental Treatment8 Interventions

INDUCTION: Patients receive pembrolizumab IV over 25-40 minutes on day 1 of cycles 1-4. Patients also receive gemcitabine hydrochloride intravesically on days 1, 8 and 15 of cycles 1 and 2. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning cycle 5, patients with no evidence of disease after induction receive pembrolizumab IV over 25-40 minutes and gemcitabine intravesically on day 1 of each cycle. Treatment repeats every 3 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients with T1 tumors undergo a re-staging TURBT within 60 days of registration. Patients also undergo urine and blood sample collection, bladder biopsy, cystoscopy, CT and MRI throughout the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cystoscopy

2016

Completed Phase 4

~810

Biopsy

2014

Completed Phase 4

~1090