A study of EP0031 and drug combination for patients with advanced cancers having changes in the RET gene

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What is this study about?

This study is looking at people who have advanced cancers with changes in a gene called RET. When the RET gene is altered, it can cause different types of cancer to grow. The study will test a medicine called EP0031, which is given as a capsule by mouth. Some people in the study may also receive standard chemotherapy medicines including cisplatin, carboplatin, or pemetrexed, which are given through a vein. The main types of cancer being studied include lung cancer (specifically a type called non-small cell lung cancer or NSCLC with RET fusion) and a type of thyroid cancer called medullary thyroid cancer or MTC with RET mutation. The study also includes people with other types of cancer that have RET changes. Some people joining the study will have already received treatment with other RET-targeted medicines, while others will not have received these treatments before.

The purpose of the study is to find out if EP0031 is safe and how well it works in treating cancers with RET changes. The study is divided into different parts called modules. Module A will look at the safety of EP0031 and help determine the right dose to use. Modules B and C will test how well EP0031 works at shrinking tumors and will continue to monitor safety. The study will measure how tumors respond to treatment, how long the response lasts, and how long people live without their cancer getting worse. For some people in the study, tissue samples from their tumor may be taken before and during treatment to better understand how the medicine works.

During the study, people will take EP0031 regularly and visit the study site for check-ups. These visits will include physical examinations, blood tests, heart monitoring with an ECG, and scans to see how the cancer is responding to treatment. The study doctors will watch for any side effects and measure the amount of medicine in the blood to understand how the body processes it. Different groups of people will be placed into different cohorts based on their type of cancer, whether they have received previous RET-targeted treatment, and other factors. The study will continue until enough information is gathered about the safety and effectiveness of EP0031 in treating these types of cancer.

1 Initial treatment period

The treatment will begin after enrollment into one of the study groups based on the specific cancer type and previous treatments received.

The study medication EP0031 will be administered orally in capsule form. This means the medication is taken by mouth.

The specific dose and frequency of EP0031 will be determined based on the assigned study group and will be provided by the treating physician.

Treatment will continue on a regular schedule as determined by the study protocol for the assigned group.

2 Regular monitoring visits

Throughout the treatment period, regular visits will be scheduled to monitor health and treatment response.

During these visits, physical examinations will be performed to assess overall health status.

Vital signs will be measured, including blood pressure, heart rate, temperature, and breathing rate.

Blood samples will be collected for laboratory tests to monitor organ function and detect any changes in blood parameters.

Electrocardiogram tests will be performed to monitor heart electrical activity and rhythm.

Imaging scans will be conducted at scheduled intervals to measure tumor size and assess treatment response according to RECIST v1.1 criteria, which is a standardized method for evaluating whether tumors are shrinking, staying the same, or growing.

3 Optional biopsy procedure

For certain study groups, a tumor biopsy may be performed if the tumor is accessible and the procedure can be done safely.

A biopsy involves taking a small sample of tumor tissue for analysis.

This procedure is optional and will only be performed with consent and if the treating physician determines it is technically feasible with minimal risk.

The biopsy helps evaluate how the tumor is responding to treatment at the cellular level.

4 Additional treatment for specific groups

Some study groups may involve combination therapy with chemotherapy agents in addition to EP0031.

If assigned to a combination therapy group, cisplatin, carboplatin, or pemetrexed may be administered through intravenous infusion, which means the medication is given directly into a vein.

The specific chemotherapy agents, doses, and schedule will be determined based on the assigned treatment group and will be explained by the treating physician.

These medications are standard chemotherapy drugs used to treat various types of cancer.

5 Safety assessments

Throughout the study, any adverse events or side effects experienced will be recorded and evaluated.

Adverse events refer to any unwanted or harmful reactions that may occur during treatment.

Serious adverse events are more severe reactions that require immediate medical attention and will be closely monitored.

The treating physician will assess the severity and relationship of any side effects to the study medication.

Regular laboratory tests will monitor liver function, kidney function, blood cell counts, and other important health indicators.

6 Pharmacokinetic assessments

Blood samples will be collected at specific time points to measure the levels of EP0031 in the bloodstream.

Pharmacokinetic assessments measure how the body absorbs, distributes, and eliminates the medication over time.

These measurements help determine how long the medication stays in the body and how it is processed.

The timing of these blood draws will be scheduled around the medication dosing and will be explained in advance.

7 Ongoing treatment and response evaluation

Treatment with EP0031 will continue as long as the cancer is responding to therapy and side effects remain manageable.

Tumor measurements will be assessed regularly to determine objective response rate, which indicates whether the tumor is shrinking.

Duration of response measures how long the tumor continues to respond to treatment.

Progression-free survival refers to the length of time during and after treatment that the cancer does not grow or spread.

Overall survival measures the length of time from the start of treatment.

The treating physician will discuss treatment response and any necessary adjustments to the treatment plan.

8 End of treatment period

Treatment will continue until the cancer progresses, unacceptable side effects occur, or another reason for discontinuation arises.

A final assessment will be performed at the end of treatment, including physical examination, laboratory tests, and imaging scans.

Follow-up visits may be scheduled after treatment ends to monitor long-term outcomes and health status.

Who Can Join the Study?

You must be 18 years of age or older
You must have a diagnosis of advanced solid tumour, which means a cancer that has grown or spread to other parts of the body
Your cancer must have a specific change in a gene called RET, which can be confirmed through testing of your tumour tissue or blood sample
You must be able to swallow and keep down oral medication
You must have a performance status of 0 or 1, which means you are able to carry out normal activities or have only minor limitations in your daily activities
Your life expectancy must be more than 3 months
You must be willing to take part in all required tests and procedures during the study
You must be able to understand the study and provide written agreement to participate before any study procedures begin
Depending on your specific type of cancer, you may need to have measurable disease, which means your tumour can be seen and measured on scans
For patients with lung cancer with RET fusion: You may need to have received one prior treatment with a first-generation RET-targeted therapy, or you may not have received any RET-targeted therapy before
For patients with medullary thyroid cancer with RET mutation: You may need to have received one prior first-generation RET-targeted therapy, or you may not have received any RET-targeted therapy before
For patients with other solid tumours with RET fusions: You may need to have received one prior first-generation RET-targeted therapy, or you may not have received any RET-targeted therapy before
You may have received up to three prior lines of standard cancer treatments, depending on your cancer type
Some patients may need to have a tumour that can be safely biopsied, which means a small sample of the tumour can be taken for testing
You must be informed about other available treatment options, including approved RET-targeted therapies

Who Cannot Join the Study?

The specific exclusion criteria (reasons why you cannot participate) have not been provided in the available study information
Generally, clinical trials have rules about who cannot join to keep participants safe and ensure the study results are accurate
Common reasons patients may not be able to join cancer studies include having certain other medical conditions, taking specific medications, or having recent treatments
Your doctor will review all requirements with you to determine if this study is right for you

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Institut Gustave Roussy	Villejuif	France
Hospital Universitario Hm Sanchinarro	Madrid	Spain

Other Sites

Site Name	City	Country
Centro Di Riferimento Oncologico Di Aviano	Aviano	Italy
Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano	Italy
Charite Universitaetsmedizin Berlin KöR	Berlin	Germany
Ludwig Maximilian University Of Munich	Munich	Germany
Hospital Universitario 12 De Octubre	Madrid	Spain
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Centre Francois Baclesse	Caen	France
Vall D Hebron Institute Of Oncology	Barcelona	Spain
Hospital Universitario Virgen De La Victoria	Malaga	Spain
Complejo Hospitalario Universitario Insular Materno Infantil	Las Palmas De Gran Canaria	Spain
Udwcmwojnl Mopsrde Ctjzpv Hgqocyffajpcdqlrr	Hamburg	Germany
Mmlhuiu Uyroqmexbu Ox Gphcrg	Gdansk	Poland
Uwycveymyy Hlzztqqo Cketehr	Cologne	Germany
Afvoahbsnr Prhwzchm Hnbudonq Dv Msaafjqfe	Marseille	France
Nlncnenn Ilsrlpjz Oousykodi Iyu Mxghr Sarxaaylxxtqxxjlwlqspmryeklc Iecpqrzl Bqczvmfd	Cracow	Poland
Gmumsx Ufunlgjpea Ftrtjcwdz	Frankfurt	Germany
Ahyxxdj Uodpg Smaulypgz Lnqbaz Du Beaebeb	Bologna	Italy
Clgdqy Lpca Bzqzat	Lyon	France
Ihkewy Ivqrwhrt Fvshymlklnrdk Opvcikficut	Rome	Italy
Hxaxuurl Urqidejmzngsr dp A Cbrrqo	A Coruna Galicia	Spain

Trial status

Country	Status	Recruitment Start
France	Recruiting	01.12.2022
Germany	Recruiting	01.12.2022
Italy	Recruiting	01.12.2022
Poland	Not yet recruiting	01.12.2022
Spain	Recruiting	01.12.2022

Trial locations

Investigated drugs:

EP0031 is an experimental medication being tested in this clinical trial. It is given as a single treatment (monotherapy) to patients with advanced cancers that have specific changes in a gene called RET. The study is looking at how safe this medication is, how well patients tolerate it, how the body processes it, and whether it helps treat these types of cancers. This medication is being tested in patients who may have already received other similar treatments or who have not received such treatments before.

Investigated diseases:

RET-altered malignancies – RET-altered malignancies are a group of cancers that have specific changes in the RET gene, which provides instructions for making a protein involved in cell signaling. These alterations can occur as gene fusions, where the RET gene joins with another gene, or as mutations that change the gene’s structure. When the RET gene is altered, it can cause cells to grow and divide uncontrollably, leading to tumor formation. These genetic changes can be found in various types of cancers, including lung cancer, thyroid cancer, and other solid tumors. The disease progresses as the abnormal cells continue to multiply and may spread to other parts of the body. RET alterations are considered important targets for specific cancer therapies.

Non-small cell lung cancer – Non-small cell lung cancer is the most common type of lung cancer, accounting for approximately 85% of all lung cancer cases. It begins when cells in the lung start to grow abnormally and form tumors in the lung tissue. This type of cancer grows and spreads more slowly than small cell lung cancer. The disease can progress from early stages affecting only the lung to advanced stages where it spreads to lymph nodes and other organs. RET fusion positive non-small cell lung cancer is a specific subtype where the RET gene has joined with another gene, driving the cancer’s growth. As the disease advances, tumors may increase in size and number, affecting lung function and spreading to distant sites in the body.

Trial ID:

2022-501636-42-00

Protocol code:

EP0031-101

NCT ID:

NCT05443126

Trial Phase:

Human Pharmacology (Phase I) – Other

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A study of EP0031 and drug combination for patients with advanced cancers having changes in the RET gene

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?