Parsing the protocol

I’m as a big a fan as anyone when it comes to medical research. Without the opportunity to participate in clinical trials, I would have been dead years ago.

However, I think it is a misperception to imply that accrual to trials is simply a problem of access.

Access may well be problem number one. If you don’t know, you can’t act. But it is hardly as simple as that.

First, you have to qualify. This includes a comprehensive screening process that evaluates demographics, medical history, blood and tissue tests (in the case of tissue, either archived or fresh biopsy), physical examination, performance status, vital signs, eye exams, ECG, ECHO, assessment of tumor through X-ray, CT scan or MRI.

If you jump successfully through all these hoops then you potentially are eligible.

Next, you are presented with a document referred to as an informed consent. Exactly one paragraph is devoted to the rationale as to why this therapeutic may effectively inhibit cancerous growth:

DS-1062a targets a protein called trophoblast cell-surface antigen2 (TROP2) which is found on the surface of cancer cells in large amounts. DS-1016a is made up of an antibody that binds to TROP2, and a drug of topoisomerase I inhibitor, which is called ‘MAAA-1181a’ It is thought that DS-1062a may slow tumor growth by attaching to TROP2 and releasing the drug inside the cells.

Now that you’ve had a chance to kick the tires, the rest of the 23 pages is primarily devoted to nuts and bolts of both what your commitment shall be, what theirs shall not be, as well as a comprehensive list of potential side effects.

It is stated on page one that for the purposes of this study, you will be referred to as a ‘participant’. That is an important distinction. Not patient, not person, but rather, participant.

As a ‘volunteer’, you may decide to discontinue the study at any time. However, you may also be removed. The primary reason for removal is stated as such You will be in this research study for as long as your tumor does not get larger or no new tumor is found.

But there is more:

You may be taken off the research study drug for many reasons including if:

It is considered to be in your best interest

The study treatment or procedure are found to be unsafe or ineffective

There is any problem with following study treatments and procedures

You are a female and become pregnant or plan to become pregnant

Your condition worsens

A decision is made to close the study

Or for other unforeseen reasons that make it necessary to stop you participation in the research study

After this, the risks are addressed, but not before this statement is made: If you experience side effects, they may go away after you stop taking the study drug. Some side effects can be mild; but others can be long lasting and may never go away. Some may be life-threatening or fatal.

Still interested? After reading the long list of potential side effects (which I shared in yesterday’s post), put on your altruism hat. Under ‘What are the benefits of the research study?’ is this very candid assessment: We do not know if taking part in this study will help you. This study may help researchers learn information that could help people in the future.

And then the real nitty gritty. ‘Will I be paid to take part in this research study?’ You will not be paid for participating in this study. We may use your sample and information to develop a new product or medical test to be sold. The sponsor and hospital may benefit if this happens. There are no plans to pay you if your samples are used for this purpose.

Ok then. But what about costs? Taking part in this research study might lead to added costs to you or your insurance company. You will not be charged for DS-1062a. It is possible that DS-1062a may not be continued to be supplied free for some reason, It this would occur, your research doctor will talk with you about your options. You or your insurance company will be charged for portions of your care during this research study that are considered standard care. You may be responsible for copayments and deductibles that are typical for your insurance coverage.

What if you are injured or become ill due to participation? The treating hospital will offer you the care needed to treat injuries directly resulting from taking part in this research. These treatment will be billed to your insurance company. You will be responsible for deductibles and co-payments. There are no plans to pay you or give you other compensation for the injury. You do not give up your legal rights by signing this form.

And data. That damned data. While all reasonable efforts will be made to protect the confidentiality of your protected health information, it may also be shared with the following agencies: (yada, yada, yada). And then this nugget: Some who may receive your protected health information may not have to satisfy the privacy rules and requirements. They, in fact, may share your information without your permission.

As far as accessing your own data, you have the right to it request it but ‘only after the study is completed.

There are four optional studies addended, two of which I said no to (use of archival tissue and a third thoracic biopsy). Two others I assented for, as they merely required additional blood draws and storage and potential use of remaining biological sample including tissue. Interesting to note was this bit of information though: The results obtained from samples will not be provided to you or your study doctor. The results may be published in academic journals or discussed in conference. Even in that case, your personal information will not be disclosed at all, so your privacy is strictly protected. Your sample test results may result in findings that have value. The Sponsor may gain financial benefit from these findings. You will not have any right to any of these findings or financial gain.

I like to quote Richard Pazdur of the FDA, whom I once heard say ‘People are not for clinical trials. Clinical trials are for people.’ Maybe so. And perhaps that is why it is necessary to call us participants, scrub our humanity from us.

So yes, I am grateful to medical research. But I am also highly critical. Any attempt to call this a partnership is disingenuous. A relationship, yes. But not one of equals.

Read that fine print.

One two

I had my infusion yesterday. Because the monoclonal antibody inhibitor must come frozen, it is always a ridiculously long day. Blood draw (never less than two pokes, sigh), wait for labs, thaw. And finally a titrated three hour infusion to mitigate reaction. Nine hours in the hospital, all told. I also got a flu shot yesterday, and by midnight yesterday I felt as if I had been sucker punched.

Today I moved from bed to couch to bed and back. The surreal thing is that 48 hours ago I spent five hours in my studio painting.

Although I am highly optimistic that I can get back there tomorrow, I may be dreaming. This part of cancer really sucks. The cycle of malaise that is treatment related.

I’ve got at least one more cycle to go but then I am going to pose a question, what is the likely worse case scenario if I were to take a break?

Psychologically it wears one down. I also had to sign a new protocol yesterday, as new side effects of DS-1062a have been added. As a reminder that Phase I trials are potentially no walk in the park, here is the list of adverse events which have been identified in at least 10% of subjects:

Fatigue

Nausea

Alopecia (hair loss)

Mucosal inflammation (inflammation of the lining of the mouth/digestive tract)

Infusion related-reactions, a response that may occur after the infusion of study drug. Symptoms may include fever, chills, nausea, vomiting, headache, cough, shortness of breath, severe reductions in blood pressure, dizziness and/or rash, usually of mild to moderate severity. You may show shortness of breath and severe reductions in blood pressure

Anemia, a low number of red blood cells that can cause tiredness and shortness of breath

Vomiting

Decreased appetite

Stomatitis (inflammation of lining of the mouth)

Rash

Diarrhea

The following serious side effect has been reported with the use of DS-1062a: Lung problem (interstitial lung disease), which can be life-threatening. Signs of lung problems may include trouble breathing, cough, tiredness, fever and fluid in the lungs

Based on the experience in people who received the individual components of DS-1062a and other products of the same class of this drug, several of the following have been observed:

Diarrhea

Nausea and Vomiting

Stomatitis/mucosal inflammation

Ileus (blockage in the bowels) and intestinal perforation

Infection of the large intestine with a drop in your white blood cell count (Neutropenic colitis and Neutropenic sepsis)

Disseminate intravascular coagulopathy (DIC) or a condition in which blood clots form throughout the body’s small blood vessels

A decrease in neutrophil counts

Decrease in platelet count

A decrease of red blood cells or or hemoglobin in the blood

Inflammation of the lung

Elevation of live enzymes

Decrease in renal (kidney) function as manifested by an increase in your creatinine levels

Hypersensitivity or severe allergic reactions, which can be life threatening

Chest pain, difficult of breathing that may suggest a heart problem or blockage of oxygen supplied to your heart

Blood clots

Acute cholinergic syndrome that may be manifested by diarrhea, vomiting and sweating

In addition:

Eye problems (damage in the cornea) which may include dry eyes and keratitis

Skin problems: you may develop some skin pigmentation

Allergic Reactions/Hypersensitivity

Thus far I have experienced a variety of side effects from this exhaustive list. The mundane: diarrhea, alopecia, nausea and vomiting, fatigue. NOt on the list, a significant increase in peripheral neuropathy. At times the mucositis has been over the top, dry eyes are an irritating and ongoing sensation and I experienced infusion reactions and hypersensitivity right out of the gate, with two milder episodes since. Not the worst but also not the best side effect profile. And, it would all be easier if I was having an amazing response.

But I’m not. And so at some point I have to make the QOL call. This isn’t awful but it is, at times, unquestionably unpleasant. Of course it is easier to even consider stopping knowing that something else is coming down the pike. What can’t be known is either how tolerable or efficacious any next treatments shall prove to be. And/or actual time frames.

It’s all a bit dicey. And at times also exceedingly dull.

Feeling sentimental

I was born at the tail end of 1959. My childhood, though flawed by my birth parent’s unhappy union and therefore our dysfunctional family, now feels incredibly quaint.

Once upon a time I might have used that word–quaint–with derision. But now, in a world I hardly recognize, it is with all due respect.

It was so much simpler. Five channels, two catalogs (Sears and Montgomery Wards). Keds or Buster Browns.

Once a year, The Wizard of Oz (my favorite movie then and now) would air. Sunday mornings we’d fight over who got to read the comics first. Sunday evenings were devoted to The Magical World of Disney.

Of course, there was a fair amount of discomfort. First, the fact that I was a girl and therefore a second class citizen, something I figured out rather quickly. And as a left hander, it was immediately clear that school (desks, cursive and scissors) had not been designed with me in mind. And then there was winter. Our woolen snow pants and rubber boots, which we lined with plastic bread bags so that our feet slid in more easily.

I do not begrudge progress or the future. In fact, I feel that at heart I am much more a millennial than a boomer. And I am also an optimist to my core–even if life is a shit show (and I think it’s fair to say it is), I wanna be there.

Right to the bitter end.

However, I am grateful that I have memories of a less complicated moment in history. When nothing was on demand. Gasoline smelled good (pre ethanol) as did the pungent smell of a red paper cap–from a cap gun–hit by a hammer. Vacant lots and forts and banana seat bikes.

It was glorious–in large part because of my myopia. My inability not only to see how difficult life was for some, but also how challenging adulthood would prove to be for me.

An imperfect childhood. And yet–because it was my one and only youth–precious.

xo

Twice.

In one day. Tiresome, perhaps. But sometimes I have more to say…

It occurred to me that one of my gifts is that I have never felt inferior to another.

Not as a girl, not as someone who was impoverished (far too much of my lifetime), not because of a lack of a superior education. Dysfunctional childhood, single motherdom, (not a word, but hey), terminal illness, divorce (not once, but twice). None of these things could tear me down.

Sure, there were times when I have lacked in confidence. Along the way my self-esteem has suffered a significant hit or two. However, (and this is the clincher), I never ever doubted that I had the stuff to make it through.

Belief in self. That you are indomitable…that is key.

Tear me down, I will build myself right back up again. I am a survivor. Or, in a parlance I prefer. A stayer.

I shall prevail.

xo

Mine.

Much of this past year has been intensely triggering. Nightmares have become a staple, with the 2020 version of I forgot to do my homework being I find myself in a huge crowd without a mask.

The pot has been stirred, anxiety rising to the top like scum on a pond.

Ideally, it would be splendid to have a partner during this difficult time. However, my current situation remains very much me, myself and I.

Rather than lament this fact, I have decided to embrace it. A daily studio practice, longer walks with Kumo, a return to reading. And a little bit of internal housekeeping.

Counseling has gotten me through the past fifteen years. However, some months ago I became aware that perhaps I needed a deeper dive. My friend Jim is a trauma therapist and he introduced me to the concept of EMDR. Initially I was skeptical–what is this woowoo shit? However, I am also willing to give almost anything a try. And so I did. At first it felt like an exercise in futility–keep in mind these sessions are virtual. I would talk about something, the therapist would wave a pencil back and forth (which I tracked with my eyes) and then ask me how I felt. The unfiltered response would have been something akin to WTF.

However I was committed to giving it a chance. And, to my everlasting surprise, after session three something shifted.

Sometimes I like to take an edible late in the evening. That way, just as I go to bed, the high kicks in. Before drifting off to sleep I let my thoughts unspool. On this particular evening I was recalling some things from long, long ago. And I had an aha moment.

There was a traumatic event in my childhood that correlated perfectly with a similar situation in adulthood. So perfectly that I felt a little amazed that I had never made this connection before.

It felt like solving a puzzle. And, as puzzles go, completing this section meant some other pieces fell into place.

At the crux of all this are some serious issues surrounding ownership. And trust. If I can recognize and heal some of the wounds from childhood, I can better control how I respond to that which is hurtful now.

I’ve got my work cut out for me. And all those empty squares on my calendar mean that I am going to have plenty of time in which to do it.

To self.

xo

Partee….

Of one. Things are getting a bit solitary around here. I broke up with both Blue Apron and Match.com this week. Had I not missed the deadline, OKCupid would have bitten the dust as well…

Yeah. This extrovert is transitioning to introvert. Just in time for winter.

Not such a bad thing, really. There is something inherently solid about going it alone. And I am, well, ready.

After a stint in the studio this afternoon, I took Kumo to the beach. Little boy was in heaven–literally running circles around me. And, when we got back home, I shared my rotisserie chicken. Pretty sure it was one of his best days ever.

I also cracked a bottle of white wine that I’d ordered from Italy last year. Made the executive decision to drink that whole bloody bottle. Good to the last drop.

Because this was a party, I ate FOUR snickers bars. Alright. I am taking some liberties here. They were miniatures. And yet…it was an indulgence.

I then watched the conclusion of season one of Away on Netflix. Satisfied my astronaut fixation. Without any hyperbole, I really do relate to those who go where no one else has gone. My trips are not to Mars (although I would go in a heartbeat) but rather to a decidedly less scenic but ever so important destination, tomorrow. And unlike an actual astronaut, I have the satisfaction of knowing that so very many others will eventually share my journey. That like me, they will see tomorrow. And the next day.

Not so glamorous (No NASA photo ops or swag) but hey, it still means the world. Right here, beneath our feet. Terra firma.

xo

Between the lines

Radiology reports have been seemingly impacted by the pandemic. Whereas they were once released as soon as I had a post scan consult, it now takes a week or more for them to pop up on Patient Gateway.

What my oncologists infer from my scans carries more weight, but nonetheless I like to read the reports.

Today the use of language struck me. Although this was describing my physical self, some of the same vocabulary is pertinent in an emotional sense.

From the troubling–degenerative changes and post traumatic deformity–to the potentially political: slightly shifted to the left. And then what is a negative when describing cancer–persistent–a positive in another context.

The conclusion is comforting however you view it: essentially stable.

And it’s accurate, as well. Neither great nor awful. Hanging out. Hanging in. Holding on.

Full spectrum

I am tough. Fucking tough. But also tender. And, at times, exquisitely so.

Perhaps this represents a healthy balance. But, of course, it is not quite so simple.

Once upon a time I told my mother Evalynn that just because she would do anything for me, it didn’t me she could do anything to me. It is not, I explained, like mixing hot and cold water in order to get warm.

Evalynn had no idea what I was talking about.

And me? Well, my life continues to be one of extremes. All or nothing, sometimes literally.

It’s not boring but damn, what I wouldn’t give for a bit of monotony. Humdrum. Status quo.

In medical parlance, unremarkable is as good as it gets. ‘Not particularly interesting or surprising’ according to the Oxford Dictionary.

Predictable. Tedious. Dull.

Yeah. Give me one of those. And if that means not shaken, but stirred, well, ok. I’m down with that.

To mendacity.

xo

A time of tender mercies

I have never been one to look away. Knowledge is power, right?

When I get up in the morning I make coffee, check my email and then go straight for the news.

For the first time in well, ever, I sometimes feel as if I just don’t want to know.

Global warming, the world on fire, COVID-19, rampant racism and divisiveness. We’re not coming together, we are falling apart.

It’s weird, as my own world has been imperfect for so very long now. You might think I’d be inured. As it turns out, misery does not always like company.

There is no comfort in worldwide suffering. None. Dystopia was once in the realm of imagination, a plot line to be enjoyed from the comfort of ones couch.

Sure, part of what made it all so compelling was the whiff of danger–the possibility that cataclysmic events might actually lie in the future.

But most of us thought that would be later rather than sooner.

That was before the year 2020, when the shit hit the fan all at once.

Our collective challenge is adapting on the fly. Trying to maintain a semblance of normality while also understanding that some things are never going to be the same.

The optimist in me says we can do this. The realist understands that it is not going to be easy.

Sigh of relief

I had a zoom meeting with Dr. Jessica Lin and Dr. Alice Shaw today to go over my scans. And…despite the fact that I am feeling more symptomatic, everything looks relatively unchanged from the previous scan six weeks ago.

However, Alice assured me, I know my own body and she takes my assessment seriously. Bottom line, this likely represents slow progression—too subtle for scans that are spaced six weeks apart.

The plan is to wait two weeks for another infusion of DS1062-a. Ideally I would have at least one more infusion after that, but once again after four or five weeks rather than three in the interest of side effect management.

Then we would reassess. Of course, I always want to know what my future options are. I am happy to report that there are two, a virtual wealth. First, a MEK inhibitor paired with lorlatinib, a trial which is currently enrolling. However, Alice was even more enthusiastic about a trial which is at least three months away from the clinic; a SHP2 inhibitor and lorlatinib. Because I have three known secondary mutations, (G1202R, S1206F and G1269A) Alice feels my cancer is still primarily driven by ALK–the secondary mutations representing an effort to get around ALK inhibition. Hopefully a combo will cover enough bases.

I would characterize this as good news. I already knew my cancer was progressing but I am reassured that the progression is slow. And I like the sound of two options vs one. Better yet, should I have to begin with the MEK inhibitor/lorlatinib, it will not preclude my enrollment in the SHP2 trial.

So there you go. Business as usual. I still have cancer. But I also have options.

xo