FAQs COMPETE

300 patients with Grade 1 or Grade 2 GEP-NETs are being randomized at a ratio of 2:1 by a computerized system. This means that you are twice as likely to receive RPT with n.c.a. Lutetium 177 edotreotide than the standard therapy with everolimus. Neither you nor your trial doctor will be able to choose which group you are assigned to.

• 200 patients are planned to receive RPT with n.c.a. Lutetium 177 edotreotide with a maximum of 4 cycles, administered as an infusion at 3-monthly intervals for 9 months, or until diagnosis of progression.To protect the kidneys, 30-60 minutes before each cycle with RPT an Amino-Acid Solution (AAS) is given as an infusion over 4-6 hours.
   
• 100 patients are planned to receive everolimus, 10 mg daily, administered orally as a tablet.

• you are at least 18 years old
• you have a neuroendocrine tumor of gastroenteric or pancreatic origin (GEP-NET) that started in the gastrointestinal tract or pancreas
• your GEP-NET has somatostatin receptors on its surface (SSTR+)
• your GEP-NET has spread to other parts of the body (metastatic) and cannot be removed completely by surgery

The duration of trial participation for all patients will be 30 months plus pre-examination, which can be up to 90 days. Information about any other cancer treatments that you receive or any new tumors that may develop will be collected for 5 years (60 months) after the end of the trial.

If you are assigned to the treatment with n.c.a. Lutetium 177 edotreotide, you will have an appointment at the clinic for each of the four treatment cycles, administered every three months. This will continue for nine months. A short hospital stay (one to three days) might be required for treatment depending on local regulations and your trial doctor. After completing the course of treatment, you will be contacted by the trial team every six months, for five years.

Your trial team will conduct tests to make ensure that you are ready for the treatment.

The tests may include:

• a physical examination
• blood tests and a urine test
• a pregnancy test
• a heart trace (ECG)
• a computerized tomography (CT scan) or a magnetic resonance imaging (MRI scan) for imaging and localization of the diseased tissue
• a radioactive scan to ensure your tumor has somatostatin receptors on the cell surface (SSTR+)

In order for the trial doctors to identify the tumor grade, the trial team will ask to use a sample of your tumor taken at the time of your diagnosis. You will need to have a biopsy if a suitable sample is unavailable.

You will need to complete a quality-of-life (QoL) questionnaire before the treatment can start and at set times during the trial. The questionnaire will assess how you have been feeling and what side effects, if any, you have been experiencing.

The trial team will be monitoring your health during treatment and afterwards. The trial team will tell you about possible side effects of your treatment before you start the trial. Please consult your trial doctor should you feel sick or experience any other symptoms. Your trial doctor may, depending on the severity of the side effects, give you medication to treat this side effect, prescribe a break from medication, or consider stopping the trial in consultation with you.

Medical administration of radionuclide therapies such as n.c.a. Lutetium 177 edotreotide is guided by national radiation safety regulations, which differ from country to country. As you will be emitting small quantities of the radioactive substance over a seven-day period following the RPT, you will be given precautions and recommendations to follow by the trial team, such as:

• good hydration is recommended – drink more fluids (water) than you usually do
• urinate as often as possible and observe rigorous hygiene in order to avoid risk of contamination of others (sitting down to urinate; using toilet paper after urinating; flushing the toilet twice; washing hands thoroughly and having a towel that only you use)

If you are assigned to the treatment with n.c.a. Lutetium 177 edotreotide, you will be emitting small quantities of the radioactive substance over a seven-day period following the RPT. You will be given precautions and recommendations to follow by the trial team, such as:

• limit the time visitors spend with you to 30-40 minutes per visit for 1 week after treatment.; for prolonged periods, visitors should stay more than 2 meters (6 feet) away; visitors under 15 years of age and pregnant visitors should spend less time with you.
• avoid any physical contact with children or pregnant women for 1 week
• do not sleep in the same bed as your partner for 1 week
• avoid crowded public places for 1 week

Everolimus is an immunosuppressive cancer therapy that affects the division and growth of cancer cells by blocking the enzyme mTOR. You will take everolimus in tablet form that is swallowed whole every day. This can continue for as long as it is helping you and the side effects are not severe, as agreed with your trial doctor.

The trial team will ask you to keep a diary recording each time you take everolimus. This helps your trial doctor know how many doses of treatment you have had.

You may withdraw your consent to treatment at any time; however, follow-up procedures and information will continue to be collected unless you withdraw from the trial completely. You are free to withdraw from the trial at any time. If you withdraw, your regular medical care will continue unchanged.

All treatment costs will be covered. Should travel be necessary, expenses will be covered based on travel distance and country and according to sponsorship regulations.

COMPETE is conducted predominantly in Europe, North America, South Africa and Australia, in at least 14 countries and 60 sites. You can find a full list of all participating centers at the website: clinicaltrials.gov.

Should travel be necessary, travel assistance will be offered, and expenses will be covered based on travel distance and country and according to sponsorship regulations.