Bladder Cancer > Gemcitabine Hydrochloride

Pembrolizumab + Gemcitabine for Bladder Cancer

Recruiting in Palo Alto (17 mi)

+245 other locations

Overseen By Michael E Woods

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of adding pembrolizumab to gemcitabine in treating patients with non-muscle invasive bladder cancer whose cancer does not respond to Bacillus Calmette-Guerin (BCG) treatment. Chemotherapy drugs, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the patient's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding pembrolizumab to gemcitabine may delay the return of BCG-unresponsive bladder cancer for longer period compared to gemcitabine alone.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain treatments like systemic anti-cancer therapy or radiotherapy within specific timeframes before joining the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Pembrolizumab and Gemcitabine for bladder cancer?

Pembrolizumab has been shown to improve survival in patients with advanced urothelial cancer and is approved for use in certain types of bladder cancer. Gemcitabine is commonly used in combination with other drugs for bladder cancer treatment, suggesting potential effectiveness when combined with Pembrolizumab.

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Is the combination of Pembrolizumab and Gemcitabine safe for humans?

Pembrolizumab and Gemcitabine have been studied for safety in various conditions, including bladder cancer. Gemcitabine was well tolerated in studies with few side effects, and Pembrolizumab has been approved by the FDA for certain types of bladder cancer, indicating a recognized safety profile.

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How is the drug Pembrolizumab + Gemcitabine unique for bladder cancer treatment?

Pembrolizumab + Gemcitabine is unique because it combines an immune checkpoint inhibitor (Pembrolizumab) with chemotherapy (Gemcitabine), offering a novel approach for patients who cannot tolerate traditional cisplatin-based treatments. This combination leverages the immune system to fight cancer while also using chemotherapy to target cancer cells directly.

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Eligibility Criteria

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.

Inclusion Criteria

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

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

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

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

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

My bladder cancer is high grade and not deeply invasive.

I am 18 years old or older.

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

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

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

Exclusion Criteria

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

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

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

I have had idiopathic pulmonary fibrosis or organizing pneumonia.

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

I am currently on medication for an infection.

I have been treated with specific immune therapy drugs before.

I have not had radiotherapy in the last 2 weeks.

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

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

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

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

I have active tuberculosis.

Participant Groups

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.

Group I: Treatment (pembrolizumab, gemcitabine hydrochloride) Experimental Treatment 8 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.

Gemcitabine Hydrochloride is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Gemzar for:

• Non-small cell lung cancer
• Pancreatic cancer
• Breast cancer
• Ovarian cancer

🇺🇸 Approved in United States as Gemzar for:

• Pancreatic cancer
• Non-small cell lung cancer
• Breast cancer
• Ovarian cancer

🇨🇦 Approved in Canada as Gemzar for:

• Pancreatic cancer
• Non-small cell lung cancer
• Breast cancer
• Ovarian cancer

🇯🇵 Approved in Japan as Gemzar for:

• Pancreatic cancer
• Non-small cell lung cancer
• Breast cancer
• Ovarian cancer

Find A Clinic Near You

Research locations nearby Select from list below to view details:

Trinity Health Muskegon Hospital Muskegon, MI

Valley Health System-Hematology/Oncology Westwood, NJ

Marie Yeager Cancer Center Saint Joseph, MI

Benefis Sletten Cancer Institute Great Falls, MT

More Trial Locations

Who is running the clinical trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. [2022] To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer.

2. United States pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021] The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. [2018] Pembrolizumab is a humanized monoclonal antibody that targets PD-1. In the Phase III trial KEYNOTE-045, pembrolizumab was associated with a significant overall survival benefit when compared with docetaxel, paclitaxel and vinflunine in second line metastatic urothelial carcinoma (UC). Additionally, in the first line, early results from an interim analysis of the Phase II trial Keynote-052 study indicated that pembrolizumab is efficacious for cisplatin-ineligible patients. Based on data from these trials, pembrolizumab was the most recent among the five checkpoint inhibitors tested in UC to be approved by the US FDA in May 2017. It was granted regular approval for patients with advanced-stage UC who progress after receiving platinum-based chemotherapy and accelerated approval in the first line for patients who are ineligible to receive cisplatin.

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. [2023] The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC).

5. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. [2022] There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients.

6. England pubmed.ncbi.nlm.nih.gov

Metastatic bladder cancer: advances in treatment. [2022] At present, a combination of cisplatin, methotrexate, vinblastine and doxorubicin is the most widely used chemotherapy for metastatic bladder cancer. However, long-term follow-up shows that this combination may have little effect on survival. In addition, this regimen is toxic. New agents are needed which combine efficacy with good safety profiles. Agents which have been investigated include gallium nitrate, interferon-alpha and paclitaxel both as single agents and in combination with established cytotoxic drugs. A number of studies have been conducted in bladder cancer with the novel nucleoside analogue, gemcitabine. Response rates of up to 33% have been recorded in two phase II studies. Gemcitabine was well tolerated in both studies with few of the side-effects normally associated with cytotoxic drugs. A third study is ongoing.