Studio volto a valutare l’efficacia e la sicurezza di entrectinib e crizotinib in pazienti con tumore polmonare non a piccole cellule (NSCLC) ROS1-positivo avanzato o metastatico con e senza metastasi del sistema nervoso centrale (SNC)

1. Why is this study needed? 

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. NSCLC usually develops in the tissues lining the lungs. It can spread to nearby lymph nodes and other organs. Cancers that have spread are known as ‘advanced’ cancers.

Some cancers have a change in a gene called ROS1. A gene is a section of DNA that has instructions for making the body. Cells that have a changed ROS1 gene are able to survive and grow out of control. They become cancerous tumours. NSCLC with a certain change in ROS1 are called ‘ROS1 rearrangement-positive NSCLC’ or ‘ROS1-positive NSCLC’.

Crizotinib is a medicine approved worldwide by health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) for treating ROS1-positive NSCLC that has spread. Crizotinib does not work very well when cancer has spread to the brain. Better treatments are needed for ROS1-positive NSCLC that has spread. In particular, for people with cancer that has spread to the brain.

This study is testing a medicine called entrectinib. It is being developed to treat ROS1-positive NSCLC that has spread. Entrectinib is approved by health authorities in Europe and the U.S. for the treatment of ROS1-positive NSCLC that has spread. Entrectinib is not approved in other countries.

This study aims to compare the effects of entrectinib against crizotinib in people with ROS1-positive NSCLC that has spread. 

2. Who can take part in the study?

People of at least 18 years of age with ROS1-positive NSCLC that has spread can take part in the study, This is only if they have not been treated or have only been given radiotherapy for their NSCLC. They must also be able to swallow pills.

People may not be able to take part in this study if they have certain conditions, such as heart, lung or stomach problems. People also cannot take part if they have an active infection or had another cancer within the past 3 years. People who are pregnant, or currently breastfeeding cannot take part in the study.

3. How does this study work?

People will be screened to check if they are able to participate in the study. The screening period will take place from 1 month before the start of treatment.

Everyone who joins this study will be placed into 1 of 2 groups randomly (by chance, like flipping a coin). Participants will be given either entrectinib OR crizotinib, as pills to be swallowed every day.

Participants will have an equal chance of being placed in either group. This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given.

During this study, the study doctor will see participants once a month for the first 3 months. Then about every 2 months. They will see how well the treatment is working and check for any unwanted effects participants may have. Participants will have 1 follow-up visit at 1 month after completing the study treatment, during which the study doctor will check on the participant’s wellbeing. Then, participants will have follow-up visits or telephone calls from the study doctor every 2 to 3 months for as long as they agree to it. Total time of participation in the study will depend on how participants’ cancer responds to treatment and could be more than 2 years. Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

4. What are the main results measured in this study?

The main result measured in the study to assess if the medicine has worked is how long participants live without their cancer getting worse, in those with NSCLC that has spread to the brain when they start the study.

Other key results measured in the study include:

• How long participants live without their cancer getting worse in the brain or anywhere in the body
• How many participants have a positive response to the treatment
• How much time there is between the participant’s cancer first responding to treatment and the cancer getting worse in the brain or anywhere in the body
• How long participants live
• How participants’ health and any related medical conditions impact their daily life and their ability to function and enjoy life
• How much lung cancer symptoms (such as cough, chest pain and difficulty breathing) change over time compared with the start of the trial
• The number and seriousness of any unwanted effects
• The economic value of the study treatments (based on improved ability to function and enjoy life)

5. Are there any risks or benefits in taking part in this study?

Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future.

It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.

Risks associated with the study medicines

Participants may have unwanted effects of the medicines used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects.

Entrectinib and crizotinib

Participants will be told about the known unwanted effects of entrectinib and crizotinib, and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines.

Known unwanted effects of entrectinib include feeling tired or weak, having a low number of red blood cells, swelling, feeling less hungry than usual, throwing up or wanting to throw up and pain or discomfort in the head.

Known unwanted effects of crizotinib include feeling tired, having a low number of red blood cells, swelling, feeling less hungry than usual, and a feeling of spinning, being unsteady and losing balance.

The study medicine(s) may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.