Tag Archives: clinical trials

Let’s ride

Posted on September 21, 2011 | 9 Comments

Ok. So. About that LDK378 trial…The gallery above is from my first day two weeks ago. Please note the woodchuck.  And Sarah, giving me the high five after my lead-in dose.  And how tired David looks; it was a very long day. Long enough that I had time to wander the halls, peruse the Wall of Hope and hang out in the lovely Healing Garden. Long enough that it was barely light when we left the house and quite dark when we returned home.

I’m going to directly lift from the Research Consent Form (a many paged document that you must read and sign prior to enrollment in a trial) to describe the specifics of day one:

PK run-in period (3days) in Part 1 of the study 

Pharmacokinetics (PK) is the study of the actions of a drug in the body over a period of time (eg, how it is absorbed, distributed, broken down, and excreted).

The PK run-in is a 3 day period (before you begin daily study treatment with LDK378) where you will be given a single dose of LDK378 and then have repeated blood tests to see how your body handles the drug. (The tests are called pharmacokinetics or PK tests.) About 1/3 teaspoon of blood with be drawn at each PK blood draw.

  • Day one of PK run-in:  You will have blood drawn, take one dose of LDK378, and then have blood drawn 7 more times with the 8 hours after taking LDK378.
  • Procedures performed on Day 1 of the PK run-in:
  • Physical examination
  • Vital signs
  • In addition, blood pressure and heart rate will be measured before every PK blood sample is drawn.
  • 3 consecutive  EKGS after the single dose of LDK378 and another EKG 4 hours after the dose of LDK378.
  • Additional blood for research blood test to measure biomarkers and the amount of circulating tumor cells in your blood (about 4 teaspoons). Biomarkers are substances such as proteins that may give information about how LDK378 is affecting your body.

So that is the technical run-down. In reality, it all felt rather festive.  Just as my t-shirt proclaimed, this wasn’t my first rodeo and I kind of knew what to expect. 

Not long after the first dose, I experienced some cramping and Irene performed anti-diarrhea acupuncture. That was it for drama; no other discernible side effects. 

Wouldn’t it be wonderful if my personal history of lung cancer treatments someday represented the paradigm; thus far, they have only gotten easier and become more effective.

Consider: almost immediately following my diagnosis in 2005, I endured a rather brutal lower left lobectomy. That was followed by four grueling sessions of cisplatin and taxotere. In 2008 I spent two months taking tarceva with all of the side effects and none of the benefits.

And then came crizotinib (now Xalkori). Not only were the side effects minimal, it stamped out the cancer raging in my lungs and kept it at a low smolder for almost three years.

Will the LDK378 do the same? I am hopeful. The day after my lead-in dose, I was able to walk to the top of a steep hill without stopping numerous times to catch my breath; something I’d not been able to do for some time now. I felt great.

And then, I started to feel crappy again. Which is part of why I haven’t written yet.

However, before any conclusions are leapt to, I need to add that there were several extenuating circumstances. Two weeks before my lead-in dose, I had been on a ten day course of levaquin for a sinus infection. It was the first time I’d had antibiotics in months, and a curious thing happened.

The cough and accompanying rattle in my lungs, which had persisted almost since my bout with the flu, disappeared. I had assumed both symptoms were due to the progression of my lung cancer and was actually quite startled when they cleared up.

My lead-in dose was on a Wednesday, and I didn’t have another dose (the start of continual dosing) until the following Monday. In the meantime, the feeling of low level crappy returned; aches, chills, fatigue and a cough. What the hey!

Several months ago I found an imbedded deer tick but in subsequent days did not develop a bullseye rash. However, just to rule out lymes disease as a potential cause of my current symptoms, I was tested. In addition, my circulating hormone levels and thyroid were checked; all three were normal. Alice (Dr. Shaw) called on Sunday to see how I was feeling and mentioned that the pre trial PET scan had shown more uptake in my lungs than she had anticipated.We discussed the possibility of a smoldering low level pneumonia, as areas of inflammation can light up a PET scan and be confused with cancer. Finally, yesterday I saw the ENT to rule out a lingering sinus infection. My nasal passages were clear, but we decided it might be smart to go back on another ten days of levaquin and see what happens.

So here’s hoping. The side effects from the LDK378 would seem to be non-existent. If the antibiotics do their magic, perhaps I can really get back in the saddle again. I am so ready.

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Posted in ALK mutations, clinical trial, LDK378

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Saddle up

Posted on September 11, 2011 | 9 Comments

THIS AIN'T MY FIRST RODEO

 

Wednesday morning, September 7th. Lead in dose of LDK 378 and dressed for success.

It was a long day (eleven hours not including the commute), but went quite well. Per trial protocol, I returned to MGH Thursday, Friday and Saturday morning for PK’s and blood draws. After a day off, I’ll be back again bright and early tomorrow to begin regular dosing.

I’m going to fill in the blanks, but not tonight. This tuckered cowboy is hitting the sack.

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Good news: Pfizer, Abbott and my latest scan

Posted on September 3, 2009 | 5 Comments

I headed down the highway to Boston at a little past six in the morning yesterday. Those grasses that I marveled at two days prior were now covered in dew, and in the early morning light it looked like so much pink froth.  Incredible!

Traffic is a bear this time of day, and even with my early departure, I arrived only a few minutes prior to my 9:30 a.m. appointment.  After the white ID bracelet was placed on my wrist, (hospital jewelry) my weight, blood pressure and oxygen levels were checked. I was then led to a room and given a warm blanket.  Rosalba did my blood draws. Jose provided me with a new schedule, a months supply of PF-02341066, and a hug. Irene stopped by for a chat and a wee bit of acupuncture, and Marguerite to check in and for conversation.  Dr. Shaw (Alice) gave me a brief physical and went over Monday’s scans. Happily, everything is stable.

When a radiologist reads a scan, they carefully note each nodule, micro calcification and appearance of inflammation.  My lungs have some of each. Although any of these features could indicate disease, they may also represent scarring and inflammation that is benign.  Stability, or a lack of visual change, is a very reassuring indication (surpassed only by the ever hoped for complete resolution).

As of October 1st, I will have been on the trial drug for one year.  A year of stability is huge.  I have stage IV NSCLC and I have gone for almost an entire year without progression of disease, AND I have felt great.  If you’re not jumping up and down yet, start now:  statistically speaking, I should probably be dead, and not only am I still alive, I am not sick.  I feel great.  This really is flipping amazing.

Yesterday the New York Times had an article about Pfizer’s current focus on developing new drugs to treat cancer (click here). Pfizer is the largest pharmaceutical company in the world, and in the past oncology has not been one of their top focuses. They are also the maker of the experimental drug (PF-02341066) that is responsible for the halt of my lung cancer.

This article comes on the heels of an announcement that Pfizer will collaborate with Abbott Laboratories to develop a test to identify genetic mutations in NSLC (click here). Abbott’s test shall be specifically designed to search for the ALK mutation present in approximately 6-7% of tumors, in order to determine who will best benefit from treatment with PF-02341066.

It is clear that both Pfizer and Abbott see great promise in targeted therapies and are prepared to pour a lot of time and money into research and development.  I couldn’t be happier. It’s good to have some very big guns up at the front in the war against cancer.  It’s a real morale booster for those of us in the trenches.

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The “Now you see it, now you don’t” scan

Posted on August 10, 2009 | Leave a comment

Before I move on, I thought we’d take one last, long view of the before and after CT scans of my lungs. The scan on top was taken on September 16th of 2008 two weeks prior to starting the PF-02341066 trial. The lower scan was taken seven weeks after my lead-in dose (taken one week before starting regular doses) on November 19th.

beforeandafterlinneacancerslice1beforeandafterlinneacancerslice2 I had been receiving scans every three months for three years at the time of the September 2008 scan.  They had gone from questionable to progressively worse. “Interval increase in size and number of multiple bilateral pulmonary nodules is consistent with progression of metastatic disease”, read a report from August of 2007.

In stark contrast, the radiology report from November 19th of 2008 read: “Marked interval improvement of bilateral pulmonary lesions, with near complete resolution.  Small remaining lesions, left lower lung septal thickening, and left pleural effusion as above.”

I should point out that radiologist’s reports are, by necessity, very conservative in their wording.  Keeping this in mind, “near complete resolution” practically gushed with enthusiasm.

The scan from September illustrates clearly how far the cancer had advanced. The remaining upper lobe of my left lung was literally clouded with malignant nodules.  My right lung also shows a diffuse haziness indicating the spread of disease.  I had once again developed a hacking cough and increasing shortness of breath, and it was no longer possible to engage in many of the activities I had previously.  I was losing ground in my battle with cancer and it seemed inevitable that I would have to concede defeat.

But that was before PF-02341066.  Now I could literally and figuratively breathe again.  I was yet at war, but at long last I had a victory.

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PF-02341066 trial moving to Phase III

Posted on August 6, 2009 | 11 Comments

David, Peter and I drove to Boston early this morning for my routine trial appointment. The trial team has decided that I only need to come to the hospital once a month now.   My scan regimen has changed slightly as well. Although I must still have scans every two months, it won’t be necessary to get the abdominal scan each time. That means no more barium milkshakes for the moment. YES for small victories.   My oncologist, Dr. Shaw, just returned from the 13th WCLC (World Conference on Lung Cancer) in San Francisco this past weekend. At the meeting, Dr. Shaw presented updated data on the efficacy of the PF-02341066 trial. The results continue to be very promising and continue to generate excitement in the field of thoracic oncology.
The trial will soon enter Phase III. Prior to FDA approval of a drug, a controlled and randomized trial must be conducted.  It will be at multiple locations around the globe and will enroll many more people.  All those enrolling in Phase III must have the ALK mutation as well as only one failed first line therapy.  The fact that it is randomized means that some subjects will receive standardized chemo rather than the trial drug. However, should they suffer adverse effects from the standard chemo, or have progression of disease at their first scan at six weeks, they will be permitted to switch to the trial drug.  A phase II of the trial will be running simultaneously (the primary goal of Phase I is to assess for safety and dose escalation, Phase II is efficacy of the drug). Those subjects who possess the ALK mutation, but have also had more than one failed first line therapy, may enroll in a Phase II of the trial. So–bottom line–you need to have the mutation.

It was also fun to see images of my CT scans that were used as slides at the presentation. She also showed us a chart of subject response and it was interesting to see the hard data. Although my own response was characterized by my oncologist and the radiologist as “an almost total response”, statistically it is approx. a 70%  PR, or partial response.

It is beyond me how they determine such things (although Dr. Shaw explained that the methodology is to assess a two dimensional shrinkage of tumor as shown by scans). My CT scan could hardly look much better. However, I know that we are continuing to watch an area that represents either scarring or lung cancer. Only the statistical percentage is surprising, and I learned early in this journey to not pay too much attention to numbers. I just know how good I feel and that I continue to wake up every morning.  Wasn’t it Woody Allen who said that “80% of success is showing up”?
We also talked more about how the trial drug actually works.  The mutation that I have acquired (it is not inherited and so has been caused by exposure to one or more carcinogens) means that my DNA has been permanently altered, and altered in such a way that it makes cancerous cells.  The altered gene has become an oncogene:  a gene that contributes to the conversion of a normal cell into a cancerous one.  By locating where that mutation was (on the ALK gene), researchers were able to pinpoint a target.  The trial drug (PF-02341066) is a targeted therapy.   It is referred to as cancer growth blocker.  Growth factors trigger the cancer cells to divide and grow, and cancer cells are often very sensitive to them.  If these growth factors can be blocked, it is possible to stop growth and division of the cancer cells.

PF-02341066 is a Tyrosine kinase inhibitor.  This refers to the type of chemical that it blocks:  in this case, enzymes called tyrosine kinases.  These enzymes attach to a receptor on a cancerous cell and signal it to divide.  The Tyroisne kinase inhibitor stops that signal.  In layman’s terms:  my cancer has not been cured.  It has been stalled, the growth and division of cancerous cells halted, possibly indefinitely.

Realistically, it is unknown how long this drug will be effective for.  When and if it stops working, the cancer will begin to grow again.  I hope for two things: that the cancer will be held at bay for a long time, and that in the meantime, other treatments are developed.  This is the way it is with cancer.  We, all of us with cancer, are truly at the frontier.  There is so much yet to discover, and I am so grateful to those who are dedicating their life work to this end. My very existence depends on it.

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Trial Date

Posted on July 9, 2009 | 8 Comments

Yesterday was my big day at the hospital. Usually I make this trip alone, but today my husband is accompanying me as he has business in town. My labs are scheduled for 9:30 a.m., but a 6:15 am departure is necessary as it is impossible to avoid rush hour traffic at this time of day. As David is driving, I am able to sleep on the way in–always a treat.
Traffic is not too bad today, and we arrive at the hospital a little before nine. I say goodbye to David and head upstairs to the infusion wing to check in. After presenting my blue MGH card my plastic ID band, or my “jewelry”, is placed on my wrist. Sometimes it is obvious who is here for treatment, other times that fact is given away only by the plastic wristband.
There is a cart of donated novels in the waiting room and I replace the book I had borrowed and scan for any new titles that look intriguing. Infusion runs on schedule, and after a few minutes I am called. I am asked to verify my name and DOB and they check my wristband. I am then led to a little cubicle where I remove my shoes and am weighed. My blood pressure, heart rate, blood oxygen ratio and temperature are all measured. I am asked if I am in pain or fatigued. The fatigued part amuses me, as I have invariably risen at an ungodly hour to get here. I am tired, but this question refers to a different sort of fatigue; that which is brought about by cancer and it’s treatment, and so I answer no. A call is made to figure out which room is available for me, two (yea!) blankets from the warming oven are fetched, and I am led down to the part of infusion reserved for patients enrolled in clinical trials. I am put in my own room with a bed, shared bathroom, television and dvd player.
Now the fun starts (really). First is the meet and greet–as various members of my clinical trial team appear. First is Sarah, who always has a hug and a smile ready. I need to give her a urine sample, and then she does a blood draw. The technical term for all of this is PK’s, or pharmacokinetics. The purpose of this  phase I clinical trial is to understand what the trial drug does to a body, and that is in short, the definition of PK’s. Another applicable acronym is LADME, which stands for Liberation, Absorption, Distribution, Metabolism and Excretion, which is basically the pathway of the drug through the body.
In the first months of the trial, the blood/plasma sampling schedule involved several draws, and an IV would be inserted (more jewelry). Now Sarah is able to do it all in one shot. She, by the way, is an expert on the insertion of needles. If she were to meet you, within a few moments she would have visually assessed where your best vein was. No joke. This is my kind of nurse. When you get stuck as often as I do, you want it to be right the first time.
Several vials of blood are taken, as I am actually enrolled in two clinical trials. The second trial is for a technique developed at MGH that searches for very low concentrations of circulating cancer cells in the blood of patients.
Nastasha then comes in and collects my trial diary (I record the times of my morning and evening doses each day, as well as the time of the meal prior to the dose) as well as the containers for my pills. It is a good sign if they are empty, as it means no doses were missed. Nastahsa herself is going missing from my life soon, as she is going back to school to become a nurse practitioner. I am sad, but happy for her and we have pledged to stay in touch. It is amazing how close you become to the people who are in the business of saving your life.
Jose, who will be my new Nastasha, is not actually part of my team yet, but always comes in for hellos and hugs as well.
My oncologist, Dr. Alice Shaw, is early today as she has another commitment. First we go over the results of my scan. It is a good report–everything is stable. There are several little nodules in my lungs and one in particular that we are watching. It is unclear if they represent recurrent cancer or scarring, but the fact that they remain stable is reassuring. Alice then listens to my lungs, checks my ankles for swelling and answers any questions I have. I am one of those patients who is comfortable with more rather than less information, and she is very indulgent in this regard.
After Alice has left, I am visited by volunteers in pink jackets who offer me tea and toast–I take the tea. Soon Irene, one of my favorite people on the planet, appears. Irene is one the perks of my enrollment in this trial. She is part of the HOPES (Helping Our Patients and Families Through Education and Support) program at the hospital, and offers complimentary acupuncture to patients in infusion. I LOVE this part of my visit. She inquires as to what issues I would like to have addressed (stress, nausea, fatigue, pain) and I ask for the garden variety treatment. This involves three acupuncture needles in each ear, which she leaves in for 20 minutes. Invariably, I immediately feel more relaxed. Soon Marguerite comes in. If you were lost at sea (as I was when I started coming here), you would want Marguerite there. She is capable, wise, and kind. Her years as a nurse have done nothing to dull her sense of caring–she really does care deeply about her patients and inspires confidence. She has helped me address my fears on all different levels.
Now it is time for my dose. I am presented with a new diary and two pill bottles. Sarah has written the mg on the side in sharpie marker. The drug has no name yet, just a number, and Sarah reads this out to me each time, as well as confirming my name and birthday. I am given the tablets and some water and Nastasha notes the time of my dose. This concludes the official end of my trial day, although I linger a while longer just to chat.
My next stop is to see Mary Susan Convery, who is the thoracic social worker. When I  was restaged last summer, I quickly fell into a depression. I did not want my mental health to interfere with my physical health (they are so intrinsically linked) and my oncologist referred me to a psychiatrist. He prescribed an antidepressant (which I had taken before, but had been off of for 6 months) and also suggested that I talk to Mary Susan. I did not know that this was part of the role of a social worker. Mary Susan is both a resource as well as a counselor, and as her specialty is thoracic oncology, she is well acquainted with the issues I was struggling with. I have been seeing her for almost a year now, and I consider our visits  a critical component of my sense of well being.
When my appointment has concluded, I have just enough time to go to lunch before I must head over to Massachusetts Eye and Ear Infirmary for a checkup with an opthamologist. One apparent side effect of the drug has been a visual disturbance where I see light trails or ghostly shadows of objects in dim light. It is confirmed that my eyes are in good health, but that my problem is neurological in origin. It is called Palinopsia and it is a symptom rather than a pathology or disease. It is not known if it is permanent or transient, but for me it is merely troublesome and I am simply relieved that there is nothing to indicate that that the health of my eyes is at risk.
It has been a long day. My husband is waiting outside for me and we retrieve our car to begin the long drive home. I am relieved that everything was stable on my scan. I can leave for our summer vacation with a sense of well being.

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Driving into Boston…

Posted on July 6, 2009 | 2 Comments

Today I drove the 110 miles (each way) between our home and Boston to go to MGH (Massachusetts General Hospital) for a CT scan. Driving myself to these appointments is just one of the ways in which I have become more independent than I was previously. When I expressed interest in participating in the clinical trial, I was warned that it would mean both a considerable time and travel commitment on my part. These seemed small considerations given what was at stake.
The trial drug is administered orally in tablet form and I am able to take my twice daily dose at home. However, I am required to be at the hospital two days a month for blood tests and physicals. This is both for the purpose of collecting data and to monitor my health. I am also given a spiral CT scan of my chest and abdomen every two months for the same reasons.
I have received so many CT scans over the last 4 years. I just can’t dwell on things such as the secondary exposure to radiation that is part of my treatment. More of that between a rock and a hard place. Instead I focus on the fact that I am so very fortunate to have such state-of-the-art care available to me. The spiral CT scan makes early visual detection of any minute changes in the areas that are monitored possible. This provides important information as to the efficacy of the drug to my doctors and the trial researchers.
Before I was enrolled in the trial I would become very anxious a week or so prior to each scan (scanxiety). This was with good reason–as I never had a completely clean scan. These “dirty” scans meant that I could never say that I had no evidence of disease, or, “just call me NED”. This was obviously very difficult on the one hand–no respite from my disease. On the other hand, perhaps I was not as surprised and thereby more prepared emotionally for recurrence. I don’t wish to imply that it was anything but devastating to make that transition to “terminal” and I will certainly devote more time to that in another blog.
But back to the subject at hand–my bimonthly CT scans.
I really don’t get very anxious anymore. This is in part because I feel so good and am therefore more confident of a positive outcome. To be honest, when your scans are two months apart, there is very little time between them in which to get nervous.

On the day of the scan, you are required to fast for two hours prior and to check into radiology one hour before the scan.  Then they hand you two 450 mL barium sulfate “shakes” that you need to drink within the next hour.  I have begun to dread this.  I don’t know if it’s my brain or my stomach, but it just gets harder and harder to swallow (literally).  Today I felt pretty darn nauseous, and I think I will speak to my oncologist about whether or not I could take an anti-nausea medication on the day of the scan.  The last thing I want to have happen is to vomit and have to repeat the whole sequence of events.

At the time of your appointment (well, things don’t always run on schedule) you change into a johnny (why do they call them that?) and take your place in a waiting room that is always several degrees colder than comfort would dictate. Blankets from the warmer are available on request.  Sometimes the patients chat amongst themselves about various diagnoses–other times you wait in chilly silence.  When your name is called you are led to a room where an IV is put in. The nurse in this department refers to those of us who are frequent fliers as the “poker” club.  One side effect of frequent visits can be “tired” or fussy veins. Today a young man is training.  The nurse instructs him to use a pediatric needle for me, as my veins are not only tired but roly.  We are all relieved when he gets the IV into the first vein he tries.  Then it’s back to the waiting room to wait for the actual scan.

The scans themselves are no big deal.  Actually–I take that back.  You are required to hold your breath, and although that is no problem now, when I had extensive cancer in my lungs it was not easy.  For the last part of the exam, they inject a radioactive contrast agent into your IV.  After a few seconds you get a really warm feeling in your mouth and your groin.  And then, after perhaps 10 minutes on the exam table–you’re done.

Waiting for results is never easy.  Sometimes it’s several days or more:  this time I only have to wait two days, as I have an appointment with the trial team on Wednesday.  At that time I will find out whether the cancer is still being held at bay.

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