A trial looking at crizotinib for advanced cancer (CREATE)

In summary, crizotinib helped to control cancer growth in some people in the trial.  

The researchers also found that crizotinib helped to control the cancer best in people with changes to the MET and ALK genes in their cancer cells. 

There is a detailed summary of each published result below. 

The trial team haven’t produced results for people with anaplastic large cell lymphoma.

Trial design
This was a phase 2 trial. Everyone had crizotinib for as long as it worked and the side effects weren’t too bad. 

In this trial, some people had changes to the ALK or MET genes in their cancer cells. This is ALK or MET positive cancer. And some didn’t have these changes. This is ALK or MET negative cancer. The trial team tested a sample of tissue (biopsy ) to check this. 

Results for inflammatory myofibroblastic tumour (IMFT)
20 people joined this part of the trial. The researchers had the results for 19.

12 people had cancer that ALK positive cancer. Researchers looked at how well their treatment worked. They found in:

• 2 people the cancer went away completely (complete response)
• 6 people the cancer went away a little bit (partial response)
• 4 people the cancer stayed the same

7 people had cancer that was ALK negative. Researchers looked at how well their treatment worked. They found:

• in 1 person the cancer went away a little bit 
• in 5 people the cancer stayed the same
• in 1 person the cancer got worse 

The researchers say that these results show that crizotinib worked for people with this type of cancer that was ALK positive. They say it could be the standard treatment  for people who can’t have surgery with the aim to cure. 

Results for alveolar soft part sarcoma (ASPS)
48 people started treatment in this part of the trial. 3 people had cancer that got worse very quickly so they weren’t included in the analysis. The team had the results for 45.

Of those, 40 people had cancer that was MET positive. Researchers looked at how well their treatment worked. They found in:

• 1 person the cancer went away a little bit (partial response)
• 35 people the cancer stayed the same (stable disease)
• 4 people the cancer got worse

4 people had cancer that was MET negative. Researchers looked at how well their treatment worked. They found in:

• 1 person the cancer went away a little bit 
• 3 people the cancer stayed the same

They didn’t know if 1 person was MET positive or negative. Their cancer stayed the same. 

At 1 year the team looked at the number of people living without signs of their cancer getting worse. On average this was:

• about 37 out of every 100 people (37.5%) who were MET positive
• 50 out of every 100 people (50%) who were MET negative

CREATE trial - bar chart - 1 year - the number of people living without signs of their cancer getting worse

At 1 year they looked at the number of people living. This was:

• about 95 out of every 100 people (95%) who were MET positive
• 75 out of every 100 people (75%) who were MET negative

CREATE trial - bar chart - 1 year - number of people living

The trial team found that crizotinib worked best in people with alveolar soft part sarcoma that was MET positive. 

Results for a type of kidney cancer called papillary renal cell cancer type 1 (PRCC1)
23 people had treatment in this part of the trial. 

4 people had cancer that was MET positive. The team looked at how well their treatment worked. They found in:

• 2 people the cancer went away a little bit (partial response)
• 1 person the cancer stayed the same (stable disease)
• 1 person the cancer got worse

16 people had cancer that was MET negative. The team looked at how well their treatment worked. They found in:

• 1 person had cancer that went away a little bit
• 11 people had cancer that stayed the same 
• 4 people the cancer got worse

For 3 people the researchers didn’t know if their cancer was MET positive or negative. The team looked at how well their treatment worked. They found in:

• 1 person the cancer that went away a little bit
• 1 person the cancer stayed the same 
• 1 person the cancer got worse

At 1 year the team looked at the how many people were living without signs of their cancer getting worse. On average this was:

• 75 out of every 100 people (75%) who were MET positive
• just under 30 out of every 100 people (27%) who were MET negative

CREATE trial - bar chart - At 1 year the team looked at the how many people were living without signs of their cancer getting worse

At 1 year they looked at the number of people living. On average this was:

• about 75 out of every 100 people (75%) who were MET positive
• just over 70 out of every 100 people (72%) who were MET negative

CREATE trial - bar chart - 1 year they looked at the number of people living

The team found that crizotinib worked for people with advanced or metastatic PRCC1. It controlled the cancer longest in people with cancer that was MET positive.

Results for clear cell sarcoma (CCSA)
28 people had treatment in this part of the trial. 26 people had cancer that was MET positive. The team looked at how well their treatment worked. They found in:

• 1 person the cancer went away a little bit (partial response)
• 17 people the cancer stayed the same (stable disease)
• 8 people the cancer got worse 

2 people had cancer that was MET negative. The team looked at how well their treatment worked. They found in:

• 1 person the cancer stayed the same 
• 1 person the cancer got worse

They looked at the average length of time before the cancer started to grow again. This was on average:

• 131 days in people who were MET positive
• 96 days in people who were MET negative 

Researchers concluded that crizotinib worked for people with clear cell sarcoma that was MET positive. The team say it worked as well as some other treatments. These treatments were a chemotherapy drug called doxorubicin and a targeted drug called pazopanib. 

Results for alveolar rhabdomyosarcoma (ARMS)
13 people had treatment in this part of the trial. 5 people had cancer that got worse very quickly so they weren’t included on the analysis. The team had the results for 8 people.

7 people had cancer that was MET positive and ALK negative. The team looked at how well their treatment worked. In:

• 1 person the cancer went away a little bit (partial response)
• 6 people the cancer got worse

1 person had cancer that was MET and ALK negative.  And their cancer got worse. 

This part of the trial stopped recruiting people earlier than planned as treatment wasn’t working. The team found that crizotinib didn’t work for people with alveolar rhabdomyosarcoma (ARMS). But the researchers say this is a difficult type of cancer to treat. 

All trial results help doctors and researchers understand more about different cancers and the best way to treat them. 

Side effects
Some of the common side effects of crizotinib included: 

• feeling or being sick
• tiredness
• diarrhoea or constipation
• blurred vision
• body swelling 
• weight loss

Conclusion
The trial team concluded that crizotinib helped to control the cancer in these rare cancer types. Although it didn’t work for people with alveolar rhabdomyosarcoma (ARMS). 

Researchers say crizotinib worked best for people who had ALK or MET positive cancer. And that it worked best for people who had inflammatory myofibroblastic tumour (IMFT).

For  some people it didn’t shrink the cancer as much as researchers had hoped. 

The team found most of the side effects were manageable. 

All trial results help doctors and researchers understand more about different cancers and the best way to treat them. The trial has also helped them learn more about how cancer cells work in these cancer types which will be very useful in the future.

Where this information comes from    
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.