VanSel1 drug trial Cycle 2 Days 16-21

One more dose of selumetanib tonight and Steve will have finished the third week of cycle 2 of the VanSel1 clinical drug trial.  Just one more week to go before we know whether it's all been worthwhile.

When asked how he's doing these days, Steve's stock answer is that he has felt better, but it's bearable.  Which is true up to a point.  None of the horrible metallic taste associated with standard chemo.  Not a lot of nausea.  No tingly fingers or toes (peripheral neuropathy). No need for blood transfusions or problems with low white blood cell counts, compromising his immune system.

But the fatigue is still there - he has little energy, so has been taking it easy most of the time, over the last 10 weeks. Daily diarrhoea takes its toll over a sustained period. He literally feels drained, although taking imodium is usually an effective way to manage this side effect.

There have been stomach cramps and times when his appetite has all but disappeared - one day, he couldn't even finish the banana he thought he might be able to eat for one meal....Then there are times when he suddenly feels the need to eat or become nauseous.  All completely unpredictable, so no point in spending a lot of time cooking elaborate meals.  We need things which can be prepared very quickly when needed, and can be eaten in small batches. Tapas to the rescue!

However, the once awful skin rash is not very noticeable now; the cough appears to be easing off a little and yesterday, for the first time in ages, Steve ate three meals - most unusual, but encouraging.  In addition, this weekend he has seemed brighter in himself.  

So... the side effects are bearable, but not the sort of thing you would wish to live with on a daily basis, given a choice. Likewise, the knock-on impact of these side effects which make it difficult to go out, visit family and friends and travel any distance would not make for the most enjoyable or fulfilling life on a long term basis.  

But if it means that the cancer stayed stable, would you be prepared to live with those sort of restrictions, and manage those side effects, if it gave you extra time? Tough choice....but not one we have to face quite yet, and maybe not at all...We'll just have to wait and see. 

Without doubt, Steve's skin condition has improved slowly since taking a break in treatment then resuming with a lower dose. Who knows, perhaps the worst of the remaining side effects may ease off over the next week in a similar manner, albeit taking a little longer....  

On the bright side, we cheered on Oxford to a convincing win in the Boat Race today!  

And being tied to the house has meant that more progress has been made with spring cleaning, redecorating and reclaiming the garden from the wilderness that has taken over over the last five years since diagnosis, when home maintenance and gardening were the last thing on our minds.  

Busy week ahead.  More of that in a future post. I'm ending today with good news.  The European Parliament has voted in favour of new legislation which will require all clinical trials to be registered and results published on a publicly accessible data base.  What a pity we have to wait until 2016 before it comes into effect.  

Still, it's another piece in the jigsaw puzzle of beneficial changes that are on the cards, including the (Saatchi) Medical Innovation Bill (if you haven't given your support yet please follow THIS LINK and sign the petition!) and the Early Access to Medicines Scheme (EAMS) , which starts this month! 

Vansel Early Phase Drug Trail Cycle 1 Days 17- 21: Routines and reactions

Just one more dose of selumetanib tonight and Steve will have completed the first week of taking both drugs in the VanSel drug trial.  We have been getting used to changing the pattern of our daily life to fit around the drug trial requirements and facing up to the reality of side effects now that Steve's body has started to react to the treatment.

It's difficult to remember the last occasion when our meal times were regulated over a prolonged period.  We have grown accustomed to eating when hungry and grazing in between if necessary to top up blood sugar levels.  But that has had to change under the new regime.  

Steve must not eat for two hours before and one hour after taking the selumetanib capsules, which he does twice a day at 11.30 am and 11.30 pm.  That effectively means two 3 hour blocks of time every day when only water can pass his lips. Fasting time....

Mornings are generally not too difficult, although long lazy breakfasts finishing after 9.30 am and the occasional brunch are off the agenda for the time being.  However, the evenings have been a bit of a challenge.  It's only when you can't have a glass of wine or a nightcap and a nibble after 9.30pm that you realise how much you miss it!

I'm sure we will get into a new routine over time, but at the moment we find ourselves clock watching and saying, you've only got 5 minutes to finish your food and drain the cup of coffee or glass of wine before the curfew begins.  Not the way to relax and unwind!  

Until we get our eating patterns sorted out at home, we are reluctant to go out for meals where we have little or no control over when food and drink arrives.  I'm sure we will find ways of dealing with this, given time.  But for the moment, we are taking it softly, softly.

As well as establishing and getting used to new routines, we have been watching out for reactions to the trial drugs.  The most obvious side effect is on the gut - stomach cramps from time to time and more visits to the loo, but not so bad that Steve needs to take imodium every day. Nevertheless, he feels a bit vulnerable at the moment and is reluctant to stray far from home.  

On Thursday evening, another reaction manifest itself - a skin rash, which is another common side effect on the VanSel trial. It's more of a flush than a rash, mainly affecting his chest, neck and face.  Not itchy or painful, just noticeable and making him feel rather self-conscious - more ruddy farmer than tanned Adonis! However, the doctor said it's a sign of the drug working, so we are taking that as a positive.  

The change in complexion has gone hand in hand with a slight puffiness around his nose and cheeks, which is more obvious to Steve than to anyone looking at him.  However, the combination of rash and puffiness makes his skin feel tight and wearing glasses somewhat uncomfortable, even though he is using aqueous cream to keep the skin supple and factor 50 sunscreen when outdoors. 

Less easy to define is the feeling of being slightly fuzzy or out of focus in the head; not as sharp as he normally is...and perhaps a bit less energy than usual.

We will discuss all these reactions with the doctor on the next hospital visit for his usual blood tests and observations. However, although slightly unnerving and unsettling, so far these effects are nothing like as debilitating as those Steve experienced on his last two treatment regimes, and for that we are truly grateful.  

The only other thing we are trying to get our heads round is not having an "end date" for the Vansel trial.  Unlike previous treatment regimes, it won't necessarily be over after a specific number of cycles.  If the Vansel combination works for Steve, i.e. the cancer does not grow or spread and he can manage the side effects, then he could carry on taking these drugs beyond the study end date.  

That's got to be good news in terms of progression-free survival.  However, we would have to reconcile ourselves to some permanent life style changes, like many others who have to manage chronic health conditions with medication and new routines. 

But I'm getting way ahead of myself now....we won't know until mid-April when Steve has his next scan whether the drugs are doing the job we hope they are.  All we can do is sit tight and keep our fingers crossed.  Please cross yours too!  

Thank you x

Clinical trials: Clearer rules and better protection for patients

Thousands of clinical trials have not reported their results; some have not even been registered.  Information on what was done and what was found in these trials could be lost forever to doctors and researchers, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated. 

All Trials is a campaign to ensure that the results of all clinical trials are registered and reported.  You can read more and sign the petition by following the link HERE!

There is one last hurdle remaining now in clinical trial reform. The Willmott Report will secure better regulation of clinical trials in Europe, for the benefit of all. It has already been approved by the MEPs Public Health Committee and will go before the European Parliament in April. If passed, the proposed regulation of clinical trials will become law. 

You can help achieve this objective by urging your MEP to vote in favour of the Willmott Report on Clinical Trials Regulation when it goes before the European Parliament on 2nd and 3rd April.   

You can find contact details for your MEP on your local council website.  

Here is the text of a letter I have sent to our MEPs.  Please feel free to copy, adapt and paste to make it your own.  I will report responses in due course.

Dear ....MEP

I am writing to urge you to support the Willmott Report on the Clinical Trials Regulation.

I have a personal interest in this matter.  In June 2009, my husband was diagnosed with mesothelioma - a cancer caused by exposure to asbestos, for which there is currently no cure. However, we are confident that one day researchers will find a way to deal with this killer disease.  Research and clinical trials looking for a cure for mesothelioma give us a glimmer of hope on a difficult journey.  

On 3 April 2014 you will have the chance to vote in favour of greatly increasing the transparency of data obtained in clinical trials.   Once the regulation is in force all pharmaceutical companies and non-commercial sponsors of clinical trials in the European Union will have to:

• Submit a summary of results to a publicly accessible database, within a year of completing the research
• Submit a summary understandable to a layperson
• Submit the full Clinical Study Reports of trials when applying to put a medicine on the market
• Register or publish old trials, if they want to use them to back up applications for new trials
• Face financial penalties if transparency requirements are not met

These rules will apply regardless of whether the trial was successful, unsuccessful or inconclusive.

Around half of all clinical trials have not been published; some trials have not even been registered. If action is not taken urgently, information on what was done and what was found in trials could be lost forever, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated unnecessarily.  

Please will you help improve patient safety, sound science and the advancement of medicine by voting in favour of the report on 3 April?  

I look forward to writing about this important step forward in the regulation of clinical trials on the blog.  With your support, I know it will happen.  

Thank you.

Kind regards,

VanSel Phase 1 clinical drug trial

Now we know that Steve is definitely taking part in this Phase 1 study, I thought it might interest you to know a bit more about it.  If you want to know more about clinical drug trials and the difference between phase 1 and later phase trials click here, this link with take you to the Cancer research UK website where it's explained very clearly .

The purpose of the biological therapy trial is to determine whether using two drugs, vandetanib and selumetinib, in combination is effective in the treatment of cancer.  

• Vandetanib is a VEGFR (Vascular Endothelial Growth Factor Receptor) and EGFR (Epidermal Growth Factor Receptor) inhibitor; VEGF is a substance made by cells which helps new blood vesssels develop and grow. VEGR inhibitors stop cancers developing the blood vessels that they need to grow
• Selumetinib is a MEK (Mitogen Activated Kinase) inhibitor which blocks the pathway along which signals are sent to cells telling them to divide and grow

Although these types of drugs have shown to have an effect in non small cell lung cancer (NSCLC), this is the first time the drugs have been used together.  The aim is to see if combining these drugs has an increased anti-tumour effect for patients whose treatment options are limited.

Steve will be participating in the first part of this study which is for patients with any solid tumour.  The second part of this study is only for patients with non small cell lung cancer. 

The four main aims of this clinical study are to find out:

• If the two drugs can be given safely to patients when given together
• The maximum dose that can be given safely to patients
• More about the potential side effects of the drugs and how they can be managed
• What happens to vandetanib and selumetinib inside the body

The first part of the trial is a "dose escalation" study.  In this phase, 9-24 patients will receive vandetanib and a low dose of selumetinib to establish a safe dose to recommend for the next stage of the study.  If they don’t have any serious side effects, the next cohort of patients will have a higher dose of selumetinib, and so on, until they find the best dose to give. 

Steve will be one of the first people taking part at the start of cohort "5b" which means he will take a higher dose of vandetanib  than those in earlier cohorts.  We have yet to find out what dose of selumetinib he will be taking, but I imagine it must be near the top end by now, as we understand that the study will finish after six cohorts.  

The first cycle of treatment lasts 42 days.  Vandetanib tablets are taken once a day for 14 days, starting with a high ("loading") dose for the first four days to get the drug into the system, then a lower dose (the "continuous dose") for the rest of the cycle.  On day 15 you start taking selumetinib capsules each day as well as the vandetanib for the next 28 days, until the end of cycle 1.  

Not the VanSel drugs!  I will post a picture of the real thing  when we have both

There is no need for a "loading dose" of vandetanib in Cycle 2, so that lasts 28 days, taking both drugs every day.  As long as you don’t have bad side effects, you can carry on taking both drugs every day for as long as the treatment continues to help you.  You can also stop at any time, if disease progresses, if the side effects are too bad for you, or if you have simply had enough and want to stop.

The study started in December 2011, so the researchers have already gathered a lot of information about the two drugs and how they work.  Doses are now being fine tuned to get the optimum combination.  

There are a dozen or so hospital visits during cycle 1 to check on how you are doing - physical examination, blood pressure, blood samples, ECG and eye tests at different intervals - plus three occasions when bloods are taken for research over a 24 hour period, which involves hospital visits two days running (which is a bit of a pain, but avoids an overnight stay).  

In cycle 2 there are weekly check ups.  If you carry on to cycle 3 or beyond, check ups are monthly.

As with all drugs, there are side effects - the most common being diarrhoea, fatigue, nausea, mouth sores and skin disorders...plus swelling of the face and extremities, vomiting and fever.  Less common side effects are blurred vision and changes in the electrical activity of the heart and heart rhythm (hence the eye tests and ECGs).  

Hey ho!  When you read a list like that, you begin to wonder if this is a good idea.....However, not everyone experiences all of these things and there is medication to help manage these side effects.  Steve has managed before on his two previous treatment regimes and we are hopeful that he will be able to manage again this time round. 

As before when Steve has been undergoing treatment, I will try to update the blog more frequently.  If nothing else, it can be a useful record of events to refer to when faced with the usual questions by the trial team - How have you been feeling?  What have you experienced?  When?  For how long? How intense?

You may find it a bit boring as a result....not as much fun as talking about adventures and new experiences, but just as important in its own way, especially for anyone else offered the opportunity to take part in the trial who is wondering what happens. 

Life is likely to be very different for a while from next week onwards, so we will be making the most of this weekend to visit family, be sociable and enjoy some good food and wine while we can.  After that it will be onwards and upwards, we hope!

the green light

We have been in limbo these last few days, waiting for Steve's test results and news of whether he can take part in the VanSel1 drug trial.  

The hospital just phoned.

The answer is yes!

Now we have the green light, it's all systems go to start next week.  

Just time to fit in some family visits and socialising this weekend before we sail off into uncharted waters.

I will do another post with more about what we have been told will happen, after we have caught our breath and adjusted mentally to the reality of going back on trial.....

tests, tests and more tests...

After having his "baseline" scan last Friday, we were back in hospital again today for Steve to be tested to make sure he's fit enough to start the VanSel1 drug trial next week.  

It's a very thorough procedure, partly to make sure he meets the trial eligibility criteria and partly to have a baseline against which any changes to his body arising from the drugs or their side effects can be measured.  

So - what was involved?

• Physical examination, including height and weight measurements
• Vital signs (blood pressure, pulse rate and temperature)
• Blood tests 
• Urine tests
• ECG  (heart trace - three tracings over 5-10 minutes)
• Echocardiogram (a bit like an ultrasound scan, with jelly on the chest )
• Eye test - to rule out any eye conditions that might be made worse taking the study treatment

The echocardiogram was carried out at a different Oxford hospital and the eye test by a local optician, but luckily we had time to go home for lunch in between.  While we were at home, Julianna the trial nurse phoned to say that Steve's potassium levels were spot on.  No need to go back to the Cancer Centre for a top up, which would have been necessary had they been too low for the trial.  Eating all those bananas has clearly paid off!

The tests themselves were relatively straightforward.  It was only the very thorough eye tests, which involved dilating the pupils, which caused any problems.  Even though it was cloudy, the brightness on going outside after the test hurt Steve's eyes.  But he was back to normal by the time we arrived home....Must remember to take sunglasses or a baseball cap next time to shade his eyes! 

Only when they check the results of all these tests will we know if Steve can take part in the trial. 

Now we wait....

signing on the dotted line

This time least week, we thought we would be spending today in London on a tour of the Houses of Parliament, organised by the Friends of the Ashmolean Museum.  That was not to be because...

This time last Friday following a phone call from the Cancer Centre, we thought we would be spending the day in Oxford on a tour of various hospital departments, organised by the Clinical Trials Unit so that Steve could have the various tests needed to see whether he is eligible for the VanSel1 drug trial.  

Today, we weren't quite sure where we were going as the driver of the No 4 bus (which should have taken us to the hospital) lost the plot and went off route, much to the consternation of passengers...ourselves included!  However, we did eventually get back on track and arrived at the hospital on time for Steve's appointment at the Clinical Trials Unit.

We had been told that Steve would be having a whole array of tests today, with the aim of starting the drug trial next week if all is well.  However, it proved impossible to get a CT scan slot today.  As a result, everything has been shunted back a week before we've even started - always assuming, of course, that Steve "passes" the tests.

However, it was a good opportunity to meet key members of the team who will be looking after Steve if/when he goes on trial: Julianne, the clinical trial nurse, and Dr Nick, one of the trial doctors.  We had already met the other doctor, Dr Ioannis, when we picked up the information sheet last week.  

We now know that if the tests are OK, Steve definitely has a place on the trial even though he would be starting a week later than originally planned.  

He would be in a new group, Cohort 5B, which means the study has already established that the dosage level in earlier cohorts is well tolerated, without severe side effects.  He will be in the first group to get a slightly larger dose of one of the two drugs involved in the trial (both of which have been tested and found safe on their own).  

We discussed the side effects and pattern of hospital visits - more about that in a future blog, when we know for sure whether or not he will be taking part.  

Appointments now in place for a scan at the end of this week and the rest of the tests next week.  We ought to know the results by Friday 31 January and if all OK, the trial will start in early February.  

After about an hour and a half of discussion, Steve signed on the dotted line.  Consent given.  Another small step forward on the next stage of the journey....

preparations and parties

Since I last posted, there has been a significant date for us. 16 December marked four and a half years since Steve was diagnosed with mesothelioma.  I  hoped and felt, but never dared expect, that I would be able to say that when I started writing this blog.  But it's a very good feeling to pass yet another milestone on this journey!  

The last 10 days or so have been dominated by preparations and parties.  

Preparations
We have started collecting information to look at and consider carefully before we meet Steve's consultant in January to discuss options now that the mesothelioma has started to grow again.  

Andrew Lawson, doctor and fellow meso victim, has already given us some words of wisdom from his perspective as a seven year survivor.  

Barts Hospital has come back to us with details of a clinical trial of a new drug called Tremelimumab due to start in January.  Looks interesting but we are not sure whether Steve would be eligible as it appears to exclude people with a medical history of autoimmune diseases, including arthritis. Waiting for clarification on that and details of other trials currently recruiting at Barts.

We have asked the Specialist Lung Nurse team at our hospital to ensure that we talk to the consultant in January; told them we would like to know more about the Phase 1 VanSel clinical trail currently recruiting and sent links to the Barts clinical trials, so that we can have an informed discussion when we see Dr T.

Having started that ball rolling, we have at last made progress on Christmas preparations - cards printed, signed and posted; some presents on the way, others on order and due to arrive any time now (I hope!); wreath shining on the front door; the tree came inside and was dressed today, although we have yet to decorate the rooms, hang cards and distribute the ones we deliver by hand ..still, plenty of time to do that!  

Parties
Having worked hard on the preparations, we thought we deserved a bit of partying!  

The festive season kicked off with Em and Nick's engagement party, dancing until the early hours!  That was followed by Helen's "Equator Day" gathering to celebrate that she has now lived in the UK as long as she lived in Zimbabwe! 

Christmas proper kicked off on Sunday with mulled wine and mince pies at Tony's house, one of our neighbours just a few doors away, and a chance to chat with other neighbours we don't see that often.

Wride and Company (i.e. me and Steve!) travelled to London yesterday for the "office" Christmas lunch at Ronnie Scott's Jazz Club in Soho - an event which lived up to and indeed, exceeded, expectations!  In fact, it was a complete hoot, with good food and wine, prosecco on the house on arrival, party hats, streamers, poppers and balloons AND kazoos for when people had loosened up a bit (which didn't take long).  The house band were great, especially the second set where they invited requests for songs to sing in different styles, like a reggae version of Silent Night, and operatic version of Jingle Bells, Good King Wenceslas punk style....you get the picture.....

This will give you a flavour ...it's the last couple of minutes of the show - Steve is the one in the dark clapping like mad!! 



With preparations to complete and more parties to look forward to in the coming week, I doubt whether I will post again this side of Christmas.  So I will take this opportunity to wish you all well and send love from both of us to you and your families.  And very special positive thoughts and hugs to the meso warriors and their carers, and those who find themselves alone this Christmas time, but not by choice.  

Linda and Steve xx

Getting back up to speed and the start of an action plan

After being stopped in our tracks for a short while following Thursday's news that Steve's meso is on the move again, we are slowly but surely getting ourselves back up to speed - helped on our way by all the messages of support and good wishes.  Thank you all so much!  It feels wonderful to have so many people there for us, helping us move forward.  I will try to reply to you all individually, but it will take a bit of time.

Now the raw edge of the news has dulled a bit, we have been thinking about where we go from here.  One decision has been made.  Steve definitely wants to do something, rather than sit back and wait for the meso to grow and spread before taking any action.  So Option 1 has been set aside.

There is scientific evidence that mesothelioma patients who experience a relapse after being treated with pemetrexed based drugs (like Steve) may benefit from being treated with same drugs again.  You can read a summary of this Italian study by clicking here.  Our meso friend Heather confirms that this was her husband Alan's experience too.  So a further regime involving pemetrexed (aka Alimta) looks like a good fall back option to have in the bag, if all else fails.

However, Steve is keen to try something new, so we are focussing our attention on drug trails which are currently recruiting.  We know from experience last time round on the Velcade trial, that people on drug trails are monitored very closely and given lots of attention, which is always reassuring.  

We also know that drug trials are essential to find a cure for mesothelioma, so by taking part in another one, Steve would be helping others in his position in the long term.  Who knows?  He might even find himself taking the drug that is more effective than the current gold standard....  

Of course, he might find himself taking a placebo in a Phase 2 trial.....But as long as that's combined with pemetrexed (and maybe a platinum-based drug) he would be no worse off than if he had another chemo regime like the last one.

Phase 1 trials are different - everyone gets the trial drug. It's very much a step into the unknown, but it might be a leap in the right direction.  

To make an informed decision, we need relevant, detailed information about the trials on offer; what they involve; how they work; the side effects of treatment; whether Steve would be a suitable candidate.  And we need to gather this in an organised way, so that we can have a productive discussion with the consultant on 9 January.  

This morning we talked about a multi-pronged approach to move forward:

• Contact the specialist lung nurses at our cancer centre to ensure that it's the consultant we see in January (rather than a registrar) and to let him know that we want to know more about the Oxford-based VanSel-1 Phase 1 trial which he is leading, as well as his professional opinion about other drug trials within travelling distance of Oxford
• Contact Barts Clinical Research Centre with a synopsis of Steve's meso history to seek their views on whether they would consider him a potential candidate for any of the trials that are currently recruiting, including the SKOPOS trial of Trovax alongside chemo (although Steve's history of arthritis would probably rule him out of this immunotherapy trial); MESO 2, which involves adding a biological therapy drug called Ganetespib to the standard chemo; COMMAND trial which involves taking either another biological therapy drug called Defactnib or a placebo (not so good if you get the placebo and the meso continues to grow); the ADAM trial - a phase 2 study to compare the results of a drug called ADI-PEG 20 with best supporting care (again, not so good if you don't receive the trial drug)
• Contact Andrew Lawson - a doctor and fellow meso patient, to find out more about his treatment which involved drug trials abroad and whether he has any advice about those currently on offer in the UK
• Talk informally to our friend and neighbour down the road, who also happens to be an oncologist (although he doesn't work locally) 

At the moment, from our point of view, the front runners in terms of drug trials appear to be MESO 2, where at least you get standard chemo if you are not picked randomly for the trial drug, and the Oxford-based VanSel 1 trial - a step into the unknown...but isn't life like that anyway?

But enough of this stream of consciousness stuff!  Back to reality now...

I have to get a copy of today's Guardian as one of my images is featured in the magazine for the second successive week; 

we have an engagement party to look forward to this evening; a Secret Santa present to wrap and post; cards to print, sign and post; presents to think about; other meso warriors' news to catch up on as well as lots of e-mails to reply to and plans to make for what promises to be a very busy time between now and D-Day on 9 January.  Oh yes....and Christmas/New Year in between!

Big hug to all the meso warriors, especially Jan whose scan results did not bring good news and who is now so breathless when climbing the stairs and walking any great distance that she is now investigating chair lift and wheelchair options. Good luck too to Amanda and Ray, who is almost at chemo cycle 4, with cycle 5 scheduled for New Year's Eve, and Mavis who gets her scan results next week 

xxx