Study of drug combination with gemcitabine, cisplatin, carboplatin and avelumab in patients with advanced urothelial cancer to evaluate response to platinum-based chemotherapy
This trial is being conducted in Italy and focuses on patients with metastatic or locally advanced urothelial cancer. The main goal is to determine whether patients whose cancer has specific genetic changes in DDR genes respond better to platinum-based chemotherapy compared to those without these changes.
Main inclusion criteria: Participants must be at least 18 years old and able to provide informed consent. They need confirmed urothelial cancer with measurable disease and available tumor tissue for testing. Good organ function is required, including adequate kidney function with creatinine less than 2.5 mg/dl, acceptable liver function, and adequate blood counts. Patients must have a good performance status and a life expectancy of at least 6 months. They must also agree to use effective birth control during the study and for 180 days after treatment.
Main exclusion criteria: Patients cannot have previously received platinum-based chemotherapy or have active brain metastases. Those with severe kidney or liver dysfunction, uncontrolled heart conditions, or active infections requiring systemic treatment are excluded. Pregnant or breastfeeding women cannot participate, nor can those with known allergies to platinum medications or who have participated in another trial within 30 days.
Treatment approach: Patients will receive either cisplatin or carboplatin combined with gemcitabine hydrochloride through intravenous infusion. Some patients may also receive avelumab, a monoclonal antibody that helps the immune system fight cancer. The treatment period may last up to 18 months for chemotherapy and up to 24 months for avelumab. Regular scans and monitoring will track how well the treatment works and identify any side effects.
Investigational drugs: The trial involves platinum-based chemotherapy, which damages cancer cell DNA to prevent growth and division. While specific drug names aren't detailed in the trial information, the study focuses on understanding how genetic changes affect response to this treatment approach.
Study on Pre-Operative Nivolumab and Relatlimab for Adults with Stage II-IIIa Muscle-Invasive Bladder Cancer
This trial in the Netherlands evaluates treatments before surgery for muscle-invasive bladder cancer. The study tests nivolumab alone or combined with relatlimab as pre-operative therapy.
Main inclusion criteria: Participants must be at least 18 years old with muscle-invasive urothelial cancer stages T2-4a. They must be suitable for and accept radical cystectomy after consultation with a urologist. Imaging scans must show no cancer spread above the lower aorta. Women of childbearing potential need a negative pregnancy test within two weeks of starting treatment and must use highly effective contraception. Patients need adequate organ function with specific requirements for blood counts, kidney function, and liver enzymes.
Main exclusion criteria: Patients who have already received systemic therapy for their cancer are excluded. Those with cancer that is not stage II or IIIa, or with other cancer types besides muscle-invasive urothelial cancer, cannot participate. Vulnerable populations are also excluded.
Treatment approach: Participants receive either nivolumab alone or nivolumab combined with relatlimab through intravenous infusion before undergoing bladder removal surgery. The goal is to shrink tumors before surgery, making them easier to remove. Surgery should occur within 12 weeks from treatment start.
Investigational drugs: Nivolumab and relatlimab are both immune checkpoint inhibitors that help the immune system recognize and attack cancer cells more effectively. They work by blocking proteins that prevent immune cells from attacking tumors.
Study of Livmoniplimab and Budigalimab Compared to Chemotherapy for Adults with Advanced Bladder Cancer
This multi-country trial across Poland, France, Spain, and Belgium compares a new immunotherapy combination with standard chemotherapy for metastatic urothelial carcinoma.
Main inclusion criteria: Participants must have confirmed urothelial carcinoma with metastatic disease visible on imaging. The cancer must have progressed after at least 2 cycles of checkpoint inhibitor treatment. If eligible for platinum-based treatment, patients must have received it previously, either progressing within 6 months after completing it or being unable to receive it. At least one measurable tumor lesion is required, and patients must have a life expectancy of at least 3 months.
Main exclusion criteria: Patients who have not progressed on previous checkpoint inhibitor treatment cannot participate. Those outside the specified age range or who are part of vulnerable populations are excluded.
Treatment approach: Participants are randomly assigned to receive either livmoniplimab combined with budigalimab, or standard chemotherapy with paclitaxel, docetaxel, or gemcitabine. All treatments are given through intravenous infusion. The study runs until September 2028, measuring overall survival, progression-free survival, and quality of life.
Investigational drugs: Livmoniplimab and budigalimab are investigational immunotherapy medications being tested to see if they can improve survival in patients who have not responded to previous treatments. The study aims to find the most effective dose for future use.
Study on Chemo-Immunotherapy with Avelumab for Patients with Locally Advanced Urothelial Cancer
This Netherlands-based trial examines combining chemotherapy with avelumab immunotherapy for locally advanced cases.
Main inclusion criteria: Participants must be at least 18 years old with adequate kidney function (creatinine clearance at least 30 mL/min) and liver function. They need confirmed urothelial carcinoma with specific staging and must show at least stable disease after 3-4 cycles of chemotherapy with cisplatin or carboplatin plus gemcitabine. Patients must be fit for major surgery and have a WHO performance status of 0-2. Women of childbearing potential need a negative pregnancy test and adequate bone marrow function.
Main exclusion criteria: Patients with other cancer types, previous interfering treatments, serious heart problems, pregnancy or breastfeeding, drug allergies, inability to follow procedures, active infections, recent investigational drug use, uncontrolled high blood pressure, or mental health conditions affecting participation are excluded.
Treatment approach: After completing initial chemotherapy, patients receive avelumab through intravenous infusion as immunotherapy before undergoing radical surgery. The treatment aims to increase the rate of complete response before surgery, potentially making tumors easier to remove completely.
Investigational drugs: The study medication works with the immune system to help fight cancer cells, aiming to improve outcomes before surgery for patients with advanced urothelial cancer.
Study Comparing Erdafitinib with Vinflunine, Docetaxel, or Pembrolizumab for Patients with Advanced Urothelial Cancer and FGFR Gene Changes
This trial in France, Spain, and Belgium compares erdafitinib with other treatments in patients with specific FGFR gene changes.
Main inclusion criteria: Participants must be 18 years or older with confirmed transitional cell carcinoma of the urothelium. The cancer must be metastatic or surgically unresectable with documented progressive disease. Patients must have specific FGFR genetic changes and an ECOG performance status of 0-2. For one group, prior anti-PD-L1 treatment is required with no more than two previous treatments. For another group, no prior anti-PD-L1 treatment is allowed with only one previous treatment. Adequate bone marrow, liver, and kidney function is required.
Main exclusion criteria: Patients without advanced urothelial cancer, those who haven't received 1-2 prior treatments including anti-PD-L1 therapy, or those without FGFR aberrations are excluded. Age restrictions apply, and vulnerable populations may be excluded.
Treatment approach: Participants receive either erdafitinib as an oral tablet or one of the comparison treatments (vinflunine, docetaxel, or pembrolizumab) given intravenously. The study measures overall survival from randomization.
Investigational drugs: Erdafitinib targets specific FGFR genetic changes in cancer. Vinflunine and docetaxel are chemotherapy drugs that stop cancer cells from dividing. Pembrolizumab is an immunotherapy that helps the immune system attack cancer cells.
Study on Nivolumab and Ipilimumab for Patients with Advanced Urothelial Cancer After Initial Chemotherapy
This Spanish trial evaluates nivolumab and ipilimumab as maintenance therapy after initial chemotherapy.
Main inclusion criteria: Participants must be at least 18 years old with unresectable locally advanced or metastatic urothelial cancer. They must not have progressed during or after 4-6 cycles of first-line chemotherapy, confirmed by CT scan. Stage IV disease must have been present at first chemotherapy start. Patients must have completed 4-6 cycles of gemcitabine with cisplatin or carboplatin and join the trial within 3-12 weeks after the last dose. Normal organ and bone marrow function is required with specific criteria for blood counts, liver enzymes, and kidney function. Women of childbearing potential need negative pregnancy tests and must use effective birth control.
Main exclusion criteria: Patients who have had surgically removed cancer, those whose cancer progressed during or after first-line chemotherapy, or those outside the specified age range cannot participate. Certain health conditions or treatments may also exclude patients.
Treatment approach: Participants receive nivolumab and ipilimumab through intravenous infusion. Some may receive a placebo for comparison. The study monitors disease progression delay, overall survival, tumor size changes, and quality of life through questionnaires until June 2025.
Investigational drugs: Nivolumab blocks the PD-1 protein to enhance immune response against cancer. Ipilimumab inhibits CTLA-4 to boost immune system cancer-fighting ability. Both are immune checkpoint inhibitors working together to maintain disease control after chemotherapy.
Study on Reduced BCG Dwell-Time for Patients with High-Risk Urothelial Cancer
This trial across Denmark, Sweden, and Iceland tests a new BCG treatment schedule with reduced dwell time in the bladder.
Main inclusion criteria: Participants must be above 18 years old and sign an informed consent form. They need non-muscle invasive bladder cancer (NMIBC) and plan to receive BCG therapy for 1 year, including Ta high grade without CIS, CIS with or without Ta tumors, or T1 with or without CIS. Patients must be able to follow trial protocol and understand the patient information sheet both orally and in writing.
Main exclusion criteria: Patients with cancer types other than urothelial cancer, outside the specified age range, unable to follow procedures or adhere to treatment schedules, pregnant or breastfeeding, with severe or uncontrolled medical conditions, recent participation in another trial, allergic reactions to study medication, or unable to provide informed consent are excluded.
Treatment approach: BCG-medac containing weakened bacteria is administered directly into the bladder through intravesical use. Treatment involves once-weekly sessions for six weeks, followed by maintenance therapy for 12 months. The new schedule reduces the time the medication stays in the bladder during each session.
Investigational drugs: BCG therapy involves placing liquid containing weakened bacteria into the bladder through a catheter. While not harmful, it stimulates the immune system to attack cancer cells. The study evaluates whether reduced dwell time can reduce side effects while maintaining effectiveness.
Summary
The 13 ongoing clinical trials for transitional cell carcinoma metastatic represent a diverse range of treatment approaches across Europe. A notable concentration of trials is taking place in Spain, which hosts 7 different studies, followed by Italy and France. This distribution suggests these countries have established research infrastructure for bladder cancer studies.
The trials focus primarily on immunotherapy approaches, with several studies evaluating checkpoint inhibitors such as nivolumab, pembrolizumab, avelumab, and ipilimumab. These medications work by helping the immune system recognize and attack cancer cells. Several trials are investigating these drugs as maintenance therapy after initial chemotherapy, aiming to prevent cancer progression in patients who have responded to first-line treatment.
Another significant focus is on targeted therapies, particularly erdafitinib, which targets specific FGFR genetic changes in tumors. Multiple trials are exploring this medication alone or in combination with other treatments. The presence of studies comparing new immunotherapy combinations with standard chemotherapy reflects the ongoing effort to find more effective treatment options for patients whose cancer has progressed despite previous treatments.
These trials offer hope for patients with advanced bladder cancer by testing new treatment strategies and combinations. Participation in clinical trials provides access to cutting-edge treatments while contributing to medical knowledge that may benefit future patients. Patients interested in these trials should discuss eligibility and potential participation with their healthcare providers.
Spain
