Study of gemcitabine, cisplatin, and pembrolizumab before and after surgery compared to surgery alone for patients with bile duct cancer

Treatment assignment

Upon joining the trial, your treatment path will be determined through a process called randomization. This means that a computer system will randomly assign you to one of two treatment groups.

One group will receive chemotherapy medications before surgery combined with an additional medication, while the other group will proceed directly to surgery without chemotherapy beforehand.

This random assignment ensures that the trial results are fair and unbiased.

Pre-treatment procedures

If you are assigned to the group receiving treatment before surgery, certain procedures will be performed before starting the medications.

Blood samples will be collected within 10 days before the first treatment to check that your organs are functioning adequately.

Your physical performance status will be assessed within 7 days before the first dose. This assessment measures your ability to carry out daily activities.

If you have a blockage in your bile duct causing symptoms, a drainage procedure will be performed to relieve this obstruction before treatment begins.

Chemotherapy treatment phase

If assigned to the pre-surgery treatment group, you will receive three medications through intravenous infusion, which means the medications will be delivered directly into your vein.

The first medication is gemcitabine, a chemotherapy drug that works by stopping cancer cells from growing and dividing.

The second medication is cisplatin, another chemotherapy drug that damages the DNA of cancer cells to prevent them from multiplying.

The third medication is pembrolizumab, which is an immunotherapy drug that helps your immune system recognize and fight cancer cells.

The treatment will be given in cycles. Specific dosages, frequency of administration, and total duration of this treatment phase will be determined by the trial protocol.

During this phase, you will receive multiple cycles of these medications before proceeding to surgery.

Monitoring during treatment

Throughout the chemotherapy phase, your health will be closely monitored for any side effects or complications.

Blood tests will be performed regularly to measure tumor markers called CA 19-9 and CEA. These are substances in your blood that can indicate how the cancer is responding to treatment.

Imaging scans will be conducted to assess how the tumor is responding to the medications. The response will be evaluated using a standardized system called RECIST, which measures changes in tumor size.

Any adverse events or side effects will be recorded and graded according to a standardized toxicity scale.

Your quality of life will be assessed using questionnaires to understand how the treatment affects your daily activities and well-being.

Surgery

After completing the chemotherapy cycles, or immediately upon joining the trial if assigned to the surgery-first group, you will undergo an operation to remove the tumor.

The type of surgery will depend on the location and extent of your tumor.

During the operation, specific lymph nodes will be removed and examined by a pathologist to determine if cancer has spread to these nodes.

The goal of surgery is to remove all visible cancer tissue with clear margins, meaning no cancer cells are left at the edges of the removed tissue.

Post-surgery treatment

If you received chemotherapy before surgery, you may continue to receive pembrolizumab after the operation as part of the perioperative treatment plan.

The duration and schedule of this post-surgery medication will be determined by the trial protocol.

This additional treatment aims to reduce the risk of cancer returning after surgery.

Pathology examination

After surgery, the removed tissue will be examined by a pathologist to assess the treatment response.

The examination will determine if there is a complete pathologic response, meaning no living cancer cells remain, or a partial response, meaning some cancer cells were destroyed but some remain.

The pathologist will also examine whether the surgical margins are clear of cancer cells, which is called a radical resection.

Additional analysis will be performed on the tissue to look for specific biological markers that may provide information about your cancer.

Post-operative monitoring

Your recovery from surgery will be closely monitored for any complications.

Assessments will be conducted at 30 days and 90 days after surgery to evaluate for any surgical complications or mortality.

Any adverse events occurring after surgery will be documented and managed appropriately.

Follow-up phase

After completing all treatments, you will enter a follow-up period where your health will be monitored regularly.

Follow-up visits will include physical examinations, blood tests to measure tumor markers, and imaging scans to check for any signs of cancer returning.

The trial will track several outcomes including whether you remain free of cancer recurrence, whether cancer returns in the original area or spreads to distant sites, and your overall survival.

Quality of life questionnaires will continue to be administered during follow-up visits.

Blood samples may be collected to analyze circulating tumor DNA, which are small fragments of cancer DNA that can be detected in the bloodstream and may indicate disease status.

This follow-up period will continue for an extended duration to gather long-term outcome data.

Special considerations

If you have a history of Hepatitis B or Hepatitis C, your liver function will be monitored throughout the trial, and specific management protocols will be followed if the infection becomes active.

If you are living with HIV and your infection is well-controlled with antiretroviral therapy, you can participate in the trial. Your HIV specialist will work alongside the trial team to monitor your HIV viral load and immune system status throughout the study.

Your antiretroviral medications must remain stable throughout the trial, and certain drug interactions will be checked to ensure safety.

If you are of reproductive potential, you must use effective contraception during treatment and for at least 18 weeks after receiving the last dose of study medications.