Title: SIOP-PNET5-MB: An international prospective study on clinically standard-risk medulloblastoma in children older than 3 to 5 years with low-risk biological profile or average-risk biological profile - Clinical Trials Unit funding.
Funder: The Brain Tumour Charity

Abstract: Medulloblastoma is a cancer of the brain that usually affects children, adolescents and young adults. For the majority of patients treatment includes surgery, radiotherapy and chemotherapy. Unfortunately, current treatments are not always successful and where cure is achieved the side-effects of treatment can be severe. Many surviving patients are sadly left with low intelligence and other severe neurological and hormonal side-effects. There is now emerging evidence that the biological make-up of medulloblastoma has an effect on how successful treatment is and the likelihood of cure. PNET5 is a clinical trial for children, adolescents and young adults who have recently been diagnosed with medulloblastoma, in which treatment is determined by the biological markers identified in the cancer (tumour). Expert doctors (pathologists) and scientists will look at the tumour removed from patients after their surgery and decide on how a patient should be treated based on whether biological markers are present or not. There is some evidence that patients with a ‘favourable’ biological profile have a better chance of cure with current treatments than those with a ‘standard’ risk profile; and therefore it may be possible to cure these patients with less treatment and thereby reduce acute and long term toxicity. For those patients with a ‘standard’ risk biological profile, it may be possible to improve cure rates by adding a drug called Carboplatin to radiotherapy. Carboplatin is used as a radiosensitizer meaning it is added to radiotherapy to make it more effective. However, we don’t know whether these theories are true and we need to test them in a clinical trial. The clinical trial questions are: • Can we maintain cure rates if we reduce treatment in those patients who have a ‘favourable’ biological profile? Patients in this group will have less radiotherapy and chemotherapy than what is standardly given to patients with medulloblastoma. We hope that by giving less treatment patients will suffer less side-affects. • Can we improve cure rates in patients who have a ‘standard’ risk biological profile? Patients in this group will be randomly allocated to receive a chemotherapy drug called ‘carboplatin’ at the same time as radiotherapy or radiotherapy alone. By adding carboplatin we hope to make the radiotherapy more effective. In addition we will be looking at the quality of life of patients during and after treatment; and collecting samples of tumour tissue to look at the biology of the disease.

Lay abstract: Medulloblastoma is a cancer of the brain that usually affects children, adolescents and young adults. For the majority of patients treatment includes surgery, radiotherapy and chemotherapy. Unfortunately, current treatments are not always successful and where cure is achieved the side-effects of treatment can be severe. Many surviving patients are sadly left with low intelligence and other severe neurological and hormonal side-effects. There is now emerging evidence that the biological make-up of medulloblastoma has an effect on how successful treatment is and the likelihood of cure. PNET5 is a clinical trial for children, adolescents and young adults who have recently been diagnosed with medulloblastoma, in which treatment is determined by the biological markers identified in the cancer (tumour). Expert doctors (pathologists) and scientists will look at the tumour removed from patients after their surgery and decide on how a patient should be treated based on whether biological markers are present or not. There is some evidence that patients with a ‘favourable’ biological profile have a better chance of cure with current treatments than those with a ‘standard’ risk profile; and therefore it may be possible to cure these patients with less treatment and thereby reduce acute and long term toxicity. For those patients with a ‘standard’ risk biological profile, it may be possible to improve cure rates by adding a drug called Carboplatin to radiotherapy. Carboplatin is used as a radiosensitizer meaning it is added to radiotherapy to make it more effective. However, we don’t know whether these theories are true and we need to test them in a clinical trial. The clinical trial questions are: • Can we maintain cure rates if we reduce treatment in those patients who have a ‘favourable’ biological profile? Patients in this group will have less radiotherapy and chemotherapy than what is standardly given to patients with medulloblastoma. We hope that by giving less treatment patients will suffer less side-affects. • Can we improve cure rates in patients who have a ‘standard’ risk biological profile? Patients in this group will be randomly allocated to receive a chemotherapy drug called ‘carboplatin’ at the same time as radiotherapy or radiotherapy alone. By adding carboplatin we hope to make the radiotherapy more effective. In addition we will be looking at the quality of life of patients during and after treatment; and collecting samples of tumour tissue to look at the biology of the disease.

Research activity codes: 6.1 PHARMACEUTICALS;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS