A Study Testing How Pralsetinib Affects Other Medications in Patients with Advanced or Metastatic Solid Tumors

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What is this study about?

This study involves patients with advanced or metastatic solid tumors, which are cancers that have spread from where they started to other parts of the body or cannot be removed by surgery. The treatment being tested is pralsetinib, also known as Gavreto, which is given as hard capsules taken by mouth. This medication is designed to work in patients whose tumors have specific changes called RET fusions or mutations, which are abnormal changes in genes that can cause cancer to grow.

The purpose of this study is to understand how pralsetinib affects the way the body processes certain other substances and hormones. Specifically, the study will look at how pralsetinib influences substances that are broken down by specific enzymes in the body called CYP3A4, CYP2C8, and CYP2C9, as well as hormones called estradiol and norethisterone acetate. This information is important because it helps doctors understand if pralsetinib might change how other medications or hormones work when taken at the same time.

During the study, patients will receive pralsetinib at a dose of up to 400 milligrams per day for a treatment period of up to 2 years. Blood samples will be collected at different times to measure the levels of the test substances and hormones in the body. The study will compare these measurements when the substances are given alone and when they are given together with pralsetinib. This will help researchers understand if pralsetinib changes how quickly or slowly the body processes these substances. The study is open-label, which means both patients and doctors will know what treatment is being given.

1 Initial treatment period without study medication

On Day 1, a single dose of probe substrates will be administered. These are test medications used to measure how the body processes certain substances through specific liver enzymes called CYP3A4, CYP2C8, and CYP2C9. Hormones estradiol and norethisterone acetate will also be given.

Blood samples will be collected over a 24-hour period to measure the levels of these substances in the bloodstream.

2 Starting pralsetinib treatment

From Day 2 onwards, treatment with pralsetinib (also known as Gavreto) will begin.

Pralsetinib is taken by mouth in the form of hard capsules.

The medication will be taken daily to reach a stable level in the body.

3 Second testing period with study medication

After taking pralsetinib daily for a sufficient period to reach steady levels in the body, another dose of the same probe substrates and hormones will be administered.

Blood samples will again be collected over a 24-hour period to measure how pralsetinib affects the way the body processes these test substances.

This comparison will help determine if pralsetinib changes the breakdown of other medications in the body.

4 Continued treatment phase

Treatment with pralsetinib capsules will continue on a daily basis.

Regular monitoring will be conducted to assess how the body is responding to the medication and to check for any side effects.

Blood tests will be performed to monitor organ function, including liver and kidney function, blood cell counts, and other laboratory values.

5 Ongoing safety monitoring

Throughout the study, physical examinations and assessments of overall health status will be conducted.

Any side effects or changes in health will be recorded and evaluated.

The treatment will continue as long as it is beneficial and well-tolerated, or until the study is completed.

Who Can Join the Study?

You must be willing and able to take part in the study, follow all study requirements, and provide written consent before any study procedures begin.
You must be an adult patient, at least 18 years of age or older at the time of signing the consent form.
Your body mass index, which is a measure of body fat based on height and weight, must be between 18 and 32, and you must weigh at least 50 kilograms.
Your ECOG performance status, which is a scale that measures how the disease affects your daily living abilities, must be 2 or less on a scale from 0 to 5.
You must have recovered from side effects of previous treatments to a mild level or to your baseline condition, except for hair loss, inability to have children, or mild nerve damage.
You must have a confirmed diagnosis of advanced or metastatic solid tumors, which means cancer that has spread or is in a late stage, that has come back or has not responded to standard treatments, and that has a specific genetic change called an RET fusion or mutation detected by an approved test.
Your blood tests must show adequate organ function, including: enough white blood cells to fight infection, enough platelets for blood clotting, sufficient red blood cells or hemoglobin to carry oxygen, liver enzyme levels that are not too high, bilirubin levels within acceptable range, kidney function that is adequate, normal phosphorus levels in your blood, and normal blood clotting times.
At least 4 weeks must have passed since you had major surgery, radiation therapy, chemotherapy, immunotherapy, or targeted therapies, and you must have recovered from side effects. If you received certain long-acting treatments, at least 6 weeks must have passed since your last treatment.
If you are a male patient with a female partner who can become pregnant, you must agree to use a highly effective method of birth control during the study and for 90 days after the last dose of the study medication.
If you are a male patient, you must not donate sperm during the study and for at least 90 days after the last dose of the study medication.
If you are a female patient, you may participate if you have had surgery that makes pregnancy impossible or if you are past menopause, which means no menstrual periods for more than 1 year and certain hormone levels in your blood. Women without periods for 12 months or more may still be considered able to become pregnant if the lack of periods might be due to previous chemotherapy or hormone treatments.

Who Cannot Join the Study?

You cannot participate if you have brain metastases, which means cancer that has spread to the brain, unless they have been treated and are stable without symptoms for at least 2 weeks before starting the study
You cannot participate if you have leptomeningeal disease, which is cancer that has spread to the thin layers of tissue covering the brain and spinal cord
You cannot participate if you have spinal cord compression, which means pressure on the spinal cord from a tumor
You cannot participate if you have uncontrolled high blood pressure
You cannot participate if you have had a myocardial infarction, which is a heart attack, within 6 months before starting the study
You cannot participate if you have unstable angina, which is chest pain that occurs unpredictably and may signal a heart attack
You cannot participate if you have congestive heart failure, which means your heart cannot pump blood effectively enough to meet your body’s needs
You cannot participate if you have serious heart rhythm problems that are not controlled
You cannot participate if you have active bleeding or a bleeding disorder
You cannot participate if you have a known infection with HIV, hepatitis B, or hepatitis C viruses
You cannot participate if you are pregnant or breastfeeding
You cannot participate if you have received certain cancer treatments within a specific time before starting the study
You cannot participate if you are taking medications that strongly interact with the study drug

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Hospital Universitario Hm Sanchinarro	Madrid	Spain

Other Sites

Site Name	City	Country	Status
Hovmfssx Skr Pmvdj	Logrono	Spain

Trial status

Country	Status	Recruitment Start
Spain	Not yet recruiting	15.10.2025

Trial locations

Investigated drugs:

Pralsetinib

Pralsetinib (also known as Gavreto) is a cancer medicine used to treat advanced or metastatic solid tumors. In this study, it is being tested to see how it affects the way your body processes other medications and hormones.

Midazolam is a medication commonly used as a sedative or to help with sleep. In this study, it is used as a test drug to measure how pralsetinib affects the way your body breaks down certain medications that use the same processing pathway in your liver.

Repaglinide is a medication normally used to help control blood sugar levels in people with diabetes. In this study, it is used as a test drug to see how pralsetinib affects the way your body processes medications that use a specific liver pathway.

Warfarin is a blood thinner medication that helps prevent blood clots. In this study, it is used as a test drug to measure how pralsetinib affects the way your body processes medications that use another specific liver pathway.

Estradiol is a form of the hormone estrogen. In this study, it is being tested to see how pralsetinib affects the levels of this hormone in your body.

Norethisterone acetate is a form of the hormone progesterone. In this study, it is being tested to see how pralsetinib affects the levels of this hormone in your body.

Advanced Solid Tumors – Advanced solid tumors are cancers that have grown significantly in size or spread beyond their original location in the body. These tumors develop from abnormal cells in organs or tissues and continue to grow in an uncontrolled manner. The term “advanced” indicates that the cancer has progressed to a later stage where it may have invaded nearby tissues or structures. These tumors can occur in various parts of the body including the lungs, breast, colon, or other organs. As the disease progresses, the tumor may continue to grow locally or spread to distant sites through the bloodstream or lymphatic system.

Metastatic Solid Tumors – Metastatic solid tumors are cancers that have spread from their original site to other parts of the body through a process called metastasis. The cancer cells break away from the primary tumor and travel through the blood or lymphatic system to form new tumors in distant organs or tissues. Common sites where these tumors may spread include the liver, lungs, bones, or brain. The metastatic tumors consist of the same type of cancer cells as the original tumor. This represents an advanced stage of cancer where the disease has moved beyond its initial location. The progression involves cancer cells establishing themselves in new locations and continuing to grow and multiply.

Trial ID:

2025-523158-15-00

Protocol code:

RGL-RET-001

Trial Phase:

Human Pharmacology (Phase I) – Other

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A Study Testing How Pralsetinib Affects Other Medications in Patients with Advanced or Metastatic Solid Tumors

What is this study about?

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