Phase I/II study - patients with previously treated solid tumours
Research type
Research Study
Full title
A PHASE I/II, MULTICENTER, OPEN-LABEL, DOSE ESCALATION STUDY OF THE SAFETY AND PHARMACOKINETICS OF COBIMETINIB IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH PREVIOUSLY TREATED SOLID TUMORS
IRAS ID
174562
Contact name
Lynley Marshall
Contact email
Sponsor organisation
F. Hoffmann-La Roche Ltd
Eudract number
2014-004685-25
Duration of Study in the UK
6 years, 3 months, 1 days
Research summary
Summary of Research
Cobimetinib, the study medication, is being developed for use in the treatment of tumours. Cobimetinib Drug Product is supplied either as a 20-mg tablet or as a 4.8mg/mL suspension. The purpose of this study is to test the safety of cobimetinib at different dose levels and to find out what effects, good or bad, cobimetinib has on children, adolescents and young adult participants.
Patients will be invited to participate in this research study if they have a solid tumour for which previous treatment was ineffective or was associated with intolerable side effects, or if the tumour came back despite previous treatment.Participants will be enrolled in two stages: a dose-escalation stage and an expansion stage. A recommended dose will be identified in the dose-escalation stage of the study. Additional participants will be enrolled and treated at the recommended dose in the expansion stage. Treatment will be given orally in 28-day cycles once daily for 21 days, followed by no treatment for 7 days. Some participants in this study will receive cobimetinib as tablets, and some participants will receive cobimetinib as a suspension. The participant will receive treatment with the study medication, as long as the participant’s tumour has not worsened, the study treatment has not become intolerable e.g. due to severe side effects (determined by the Study Doctor in discussions with the participant/legal guardian), the participant/legal guardian or their Study Doctor decide it is in their best interest to stop the treatment or the study is ended by the study sponsor.
Approximately 70 participants (children, adolescents, and young adult patients) are expected be enrolled in this study, at approximately 30 investigative sites in Europe and North America. There may be more participants enrolled if efficacy signal is observed confirmed. This study is open to male and female participants up to 30 years of age (at the time of entering the study), who meet the study requirement
Summary of Results
Study overview
• This study was carried out to find out how safe cobimetinib (the medicine being studied) was in children and young adults with relapsed or refractory solid tumours that are thought to be caused by an overactive enzyme known as MEK, and how well it worked.
• In this study, people were treated with a drug called cobimetinib (known by its brand name, COTELLIC®). Cobimetinib is a type of cancer therapy that targets an enzyme known as MEK.
By targeting MEK with cobimetinib, the growth of cancer cells may be slowed down and the tumour may shrink.
• In this study, people were given cobimetinib, a type of targeted cancer therapy.
• The main finding was that the appropriate dose of cobimetinib for use in children was identified.
• Side effects were similar to those seen in adults treated with cobimetinib in other clinical studies.
• Cobimetinib reduced the size of some people’s tumours, but in most people their cancer either stayed the same or got worse.
• The study started in May 2016 and finished in July 2021. This summary was written after the study had ended.
• The study took place at 17 study centres – across seven countries, these were in Europe, Israel, the United Kingdom and the United States of America.
• In this study, 56 children and young adults with relapsed or refractory solid tumours took part.
• People who took part in the study were between 3 and 29 years of age.
• 33 of the 56 people who took part were boys/ young men. 23 of the 56 people who took part were girls/ young women.
• This was a ‘Phase 1/2’ study. This means that cobimetinib has been tested before in a number of adults with different cancers, but this study was the first time it had been tested in children and young adults with solid tumours.
• This was an open-label study. This means that the people taking part in the study and the study doctors knew what study medicine each person was given.
• During the study, people were given cobimetinib either as a tablet (taken by mouth) or as a suspension (taken by mouth) every day for 3 weeks, followed by a 7-day break (known as a ‘treatment cycle’). People in the study took cobimetinib until their cancer got worse, they experienced unacceptable side effects, they died or they withdrew from the study.
• When the study finished, the people who took part were asked to go back to their study centre for more visits to check their overall health.Side Effects
Side effects are medical problems (such as a headache) that happen during the study. They are described in this summary because the study doctor believes the side effects were related to the treatment in the study. Not all of the people in this study had all of the side effects. Side effects may be mild to very serious and can be different from person to person. It is important to be aware that the side effects reported here are from this single study and may be different from those seen in other studies.
Serious common side effects
A side effect is considered ‘serious’ if it is life-threatening, needs hospital care or causes lasting problems. During this study, around 7 out of every 100 people (7%) had at least one serious side effect.
Most common side effects
During this study, around 9 out of every 10 people (89%) had a side effect that was not considered serious.
The most common side effects were diarrhoea (39%), abdominal pain (20%) and feeling tired (18%).
Some people had more than one side effect – this means that they are included in more than one of the numbers above.
During this study, 6 out of 56 people (11%) decided to stop taking cobimetinib because of side effects. These side effects included eye problems (retinal detachment, keratitis and chorioretinopathy), heart rhythm disorders (QT prolongation) and difficulty in thinking or concentrating (encephalopathy). Most of these side effects occurred while the doctors were testing different doses of the study medicine and learning which was the best dose to use.
None of the people in the study died because of a side effect.
You can find information about other side effects (not shown in the sections above) on the websites listed at the end of this summary.
Other results of the study
Overall, researchers found that there were no new side effects for children and young adults who were given cobimetinib. However, they found that cobimetinib did not work as well as they expected when given as a single treatment.
How well did cobimetinib work at reducing the size of the tumours?
Researchers took measurements from scans of each person’s tumour to check whether their tumour got smaller or disappeared after taking cobimetinib. For most people in this study, their cancer did not improve when taking cobimetinib.
How well did the study medicine work?
When taking the study medicine, only a few people’s cancer got smaller (3 out of 56 people [5%]), while for most people their cancer stayed the same (33 out of 56 people [59%]). In other people, their cancer got worse (13 out of 56 people [23%]).
How has this study helped research?
The information presented here is from a single study of 56 children and young adults with relapsed or refractory solid tumours. These results helped the researchers learn more about these solid tumours and the study medicine, cobimetinib. Researchers found that there were no new side effects for children and young adults who were taking cobimetinib compared with the side effects that had already been seen in adults. However, they found that cobimetinib did not work as well as they expected when given as a single treatment.
No single study can tell us everything about the risks and benefits of a medicine. It takes lots of people in many studies to find out everything we need to know. The results from this study may be different from other studies with the same medicine.
Are there plans for other studies?
At the time of writing this summary, no more studies looking at cobimetinib in children or young adults with solid tumours are currently planned.
More information
• You can find more information about this study on the websites listed below:
• https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5BcbW9wgc64X2JjNxW-2BqMpAMbGSyAKecX2DRFKGkNdujYg-3D-3DHUmS_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI-2Fh818VtHmzFmtnfdf-2FJJzUmh7IJ0Evqe80CfU2XgffvAd2SUmZTWfcBphPweBvh2JOVsqbYqmzyXNWYhj35i8DYeoqbliqEBgSITvphsmB3r5HPCdje4vryY-2FsGXrU8KAsrwa33hGSxa4-2Fb9aS7yU2O8miXvfPEIBXr2bLtu8ew-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C37160122e9a6471de70f08da5ff80b15%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637927816182425933%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=N17nD%2BjRX4muIV49XGYk2ta80l%2B6sZ6%2BD%2FEo1eKtQt0%3D&reserved=0
• https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2Fctr-search%2Fsearch%3Fquery%3D2014-004685-25&data=05%7C01%7Capprovals%40hra.nhs.uk%7C37160122e9a6471de70f08da5ff80b15%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637927816182425933%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=V7HClJtIwVa7ckeGWrDQjYmx91T0%2BusHainDIoEv0QY%3D&reserved=0 https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbSgv9uUS1wsd00iFWSZyptH89w1tcscJeKmImtXTgMdpXh-2FXhkfwQ6rt-2BJsuTuM89PFLyMIg-2Fm5jsNtEzFrcZYHDIBHf-2FglTgSPeFWoJvUGgA6r4-2FY6eNQrk6f6cN9slf1DfgaRYFZhPig9i6NTbdls-3DGJkN_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI-2Fh818VtHmzFmtnfdf-2FJJzjupJ0uNXBS0LDY9zNXRpg3EXwCGVYZ-2BuX9dyrsiE4M8i-2FfZav-2FeA1CGc-2FS6-2FmFpL9CSYt4mBptXBI9vlQvzMlEngpxYADh-2FqNsO1zUQ2u76UeqzNSkmdVlbvqp-2FvUsENFO-2BflGkQUdykex2pDfcvYA-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C37160122e9a6471de70f08da5ff80b15%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637927816182425933%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=RPq%2F0e0ILm1atn9In50KVfstJFUmNidwhEzjVEh3Pvg%3D&reserved=0
If you would like to find out more about the results of this study, the full title of the relevant scientific paper is: “Cobimetinib in paediatric and young adult patients with relapsed or refractory solid tumours (iMATRIX-cobi): A multicentre, phase 1/2 study”.
The authors of the scientific paper are: Tanya Trippett, Helen Toledano, Quentin Campbell Hewson, Arnauld Verschuur, Anne-Marie Langevin, Isabelle Aerts and others.
The paper will be published in the journal ‘Targeted Oncology’, Who can I contact if I have questions about this study?
If you have any further questions after reading this summary:
• Visit the ForPatients platform and fill out
https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbSgv9uUS1wsd00iFWSZyptH89w1tcscJeKmImtXTgMdpXh-2FXhkfwQ6rt-2BJsuTuM89PFLyMIg-2Fm5jsNtEzFrcZYHDIBHf-2FglTgSPeFWoJvUGgA6r4-2FY6eNQrk6f6cN9slf1DfgaRYFZhPig9i6NTbdls-3DHYho_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI-2Fh818VtHmzFmtnfdf-2FJJzewaBgBqi6nmtPN-2FsSyCYWJ2kodZxniaaAvW-2BvN7Lg-2B9OVIx0gRg8rqvVxvi-2FGrPApFuob57omngbvrwYUsw9ErAGmCBMro4LYaqlCrbgp6y00ZLAV1wFkWdhDndhM-2BwyVkkaTHdGYTpNa-2F5yUf3EPg-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C37160122e9a6471de70f08da5ff80b15%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637927816182425933%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=EIsezujTbBJ7hJ8c7Wq68TL7rUZu1wvKUtineOVlBCM%3D&reserved=0
• Contact a representative at your local Roche office.
If you or your child took part in this study and you have any questions about the results: Speak with the study doctor or staff at the study hospital or clinic.
If you have questions about your/your child’s treatment: Speak to the doctor in charge of your/your child’s treatment.REC name
London - Hampstead Research Ethics Committee
REC reference
16/LO/0017
Date of REC Opinion
16 Mar 2016
REC opinion
Further Information Favourable Opinion