Tag Archives: phase I clinical trials

Revolving doors

On Monday I start my fifth first in human trial. It is, at best, a crapshoot.

Talk about not knowing if you are coming or going. Realistically, I am in a tough spot. Stability just doesn’t cut it these days—I need response.

If wishes were horses and if my ever growing to do list were enough to keep me here…But that’s not how this works.

It is time to get my will finished, even as I start a new painting. Feet in both worlds, now and nevermore. I am not ready. But I also understand that death is not open to negotiation.

The trick is keeping hope alive. And hoping my body follows suit.

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.


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.


Down and up date

My mood is a wobble.

The good news–thanks to a miracle product suggested by a nurse who works with head and neck cancers, my mucositis is finally under control. Yet there, but a tiny little brush fire. I ordered this stuff from Amazon and it’s not cheap but it is worth every penny.

I have scans again next Tuesday—because of the time off treatment they came up fast. Infusion is scheduled again two days later but I am hoping that Jess and Alice will read my scans first and we can discuss.

My ongoing issue is depression. Given that I had an infusion reaction right out of the gate, I am wondering if this could be related to cytokine release–which my smart friend Janet suggested as a possibility. I have been dealing with GI symptoms–both diarrhea and vomiting, as well as occasional chills; all of which could be attributed to cytokines. Those are manageable side effects, but being sad is not.

I continue to prepare meals, walk my dog, go to the studio. And–with social distancing observed–I am gradually becoming more social. On Saturday my friend Jim picked me up and we drove up the coast–with masks on and windows open–stopping at a restaurant on the marsh just south of Portsmouth for fried clams and a lobster roll. It was so much fun. I’ve had three other picnics in the past two weeks now; that and hiking seem to be the best sort of outing for the moment. My friends have all been super respectful when it comes to wearing masks, for which I am most grateful.

So that’s the scoop (one daily, mixed in water, for the Healios).


Crazy, crazy world

Tomorrow I shall drive to Dover NH for my second COVID-19 swab. Not because I am symptomatic but rather because I am now scheduled for an endoscopy on Monday and this is a requirement.

The endoscopy is indicated by the fact that my throat/esophagus is yet painful, almost five and 1/2 weeks out from my last infusion. Not the usual course of events. So the plan is to see if something else–perhaps a secondary infection–is responsible for my discomfort.

I am on board because part of being a participant in a phase I clinical trial is parsing out the safety profile/side effects of drug. Although I am the only person to (thus far) report mucositis effects of such sustained extant, it does not mean I am an anomaly. I might simply be the first.

This is the responsibility of being in a clinical trial that is often under appreciated. Phase I is not to test for efficacy but rather for safety. My primary responsibility is to not only take drug, but also to report back side effects.

It is empowering but also can cause one to doubt oneself. In phase I you are often the first (and sometimes only) person to report a particular side effect. However, I take this seriously. Like an astronaut, I am traveling to places uncharted and it is my obligation to note and record what I see and experience.

Duty noted.

I shall not step aside quietly

Remember the concept of noblesse oblige? That those in a place of privileged circumstance have a moral obligation to help others who are less fortunate?

That concept is being turned on its head, like everything else in the world right now.

I have been at the hospital since early this morning. Labs, EKG’s, infusion of saline and now drug. Long, long, weird day and it won’t end until evening.

This morning my nurse asked if I had driven myself from Amesbury to Boston. Yes, I replied. Two different friends had offered to help–one dropping me off, another picking me up and taking me home. But aside from the great inconvenience for them, I decided that I was likely safer driving in alone. I mean, social isolation is social isolation to the greatest degree possible and at this time, the only people I am spending any time with are those who are absolutely necessary–my oncology team.

Anyway, I explained to my nurse that given the fact that I would likely be denied a ventilator should I be unlucky enough to contract COVID-19, my best chance of survival was defense. I cannot get sick.

She replied with an anecdote illustrating that not everyone with COVID-19 wants to go the ventilator route, a reference to an older architect in a neighboring community. “How old?” I asked. 83. Old enough to be my father. And when I asked if he had survived she said no, ‘That’s why the paper did a story about him.”

Oh yes, I said. They like to suggest that it is a noble thing for those of us who are older or with a preexisting condition to step aside. And then, “Fuck that shit.

“I haven’t been fighting like hell for fifteen years to stop trying now. I deserve a continuing chance at survival just like everyone else. Ask my friends. Ask my family.”

I imagine she was somewhat taken aback. But It is not on the cancer patient to demonstrate noblesse oblige. We are the vulnerable, not the privileged.

Obviously diplomacy isn’t my strong suit.

After she left the room I pulled the once warm blankets over my head and fantasized that in the sequel to Mad Max: Fury Road I would be cast as Charlize Theron’s long lost mom.

That’s a role I’m better suited to.

Taking a breather from being brave

The last few days have been tough. I’ve now got ulcers all throughout my mouth and down my esophagus. My sinuses and ear canals hurt as well and it is my guess that anywhere I have a mucous membrane has been affected.

This has impacted both my appetite and my ability to eat. Basically I am getting down whatever I am able to and a case of powdered ensure arrived on my doorstep yesterday.

I had been told that hair loss was a possibility and three days ago it started coming out in handfuls. I’m rocking the plucked chicken look now and my follicles are all hyper sensitive. This afternoon Diane is taking me to a friend of hers for a buzz cut—somehow more dignified than heading to Super Cuts.

My usual joie de vivre and can do spirit has taken a (temporary) hit as well. I’ve spent a lot of time on the couch doing nothing, just literally riding this wave until it’s over; the wave being depression.

Even warriors have their down days–this shit gets old. On Thursday I will have my second infusion and have to hope that by pre-dosing with steroids and Benadryl we are able to avoid an infusion reaction. My team will be on high alert with epipens at the ready.

In the meantime I am trying both to be gentle with myself but also to push forward. Nobody said this would be easy. I just didn’t think it would be this hard.

But…(because I do like to end on a positive note) my breathing really is better. That is a wonderful thing and (if I believe my own pep talks) worth wading through. I can do this.

I can. And I will.

Getting it right about research

Medical Research (capital M, capital R) is often the star when cancer patients talk about their continuing survival.

I’ve sung the praises of research again and again. Without it, I’d be dead.

However, the part of the story that often gets glossed over is that medical research requires human subjects. And that particularly in phase I trials (designed to assess safety not efficacy), these human subjects are taking on quite a lot.

MTD, or maximum tolerable dose, is determined in phase I trials. You know how? Someone experiences side effects that are not tolerable. Tolerable is a word with a lot of latitude. As I begin my fourth phase I clinical trial, I can tell you that it takes both courage and an ability to navigate uncertainty and discomfort that frankly, many don’t possess.

Clinical trial participants are the unpaid labor force that moves experimental therapeutics to market. We take on enormous risk as well as additional expense. Our skin in the game is the real deal, from blood draws (thirty teaspoons at cycle one this time) and biopsies, we provide the necessary specimens. We agree to take drugs that no humans have taken before. In exchange, if we are lucky, our lives might be extended—maybe even long enough to enter yet another trial.

Because frankly, if trials are not a one and done, then they become a literal way of life. I have now spent a decade, or one sixth of my life, as a clinical trial participant. That’s a lot of heavy duty community service.

However, it wasn’t altruism but rather a desire to stay alive that led me to my participation. That in no way lessens the contribution though. Veterans of combat are honored for their service, not their motivations.

If we want to have clinical trial participants recognized as partners rather than merely participants, we need to change the way we talk about trials. Don’t just thank medical research, acknowledge as well the contribution of those individuals who ‘volunteer’ their time, tissue and finances. Recognize that medical research simply could not happen without these sacrifices.

Next time you express your gratitude to medical research, try saying this instead: “I would like to thank medical research and all those brave individuals who participated in the clinical trials that brought this drug to market.” It’s a mouthful. But frankly, it’s the least we can all do. Remind the world that without trial participants, research isn’t going any further than the lab. And I’m not just talking tissue, this is all about teamwork.

Honor that.

And so it begins

Milk thistle and dandelion tea plus a hella lot of water and I got those enzymes down more than forty points. So my biopsy was a go yesterday.

Happy to report that it all went smoothly and to my delight (the perks of a progressing cancer) the surgeon was able to go in from the side of my chest rather than straight through my left boob (no fun). This meant that A. I could watch the biopsy on a screen–not everyone’s cup of tea but I thought it was wicked cool–and B. my time in recovery was spent on my side rather than flat on my stomach; so much more comfortable.

It was a long, long day and big credit to my friend Diane who ferried me to and from. I am so very grateful for my incredible cadre of friends.

This morning a friend of Diane’s kindly picked me up at 5:30 am for the first day of the DS-1062a trial (‘DS1062a is a trophoblast cell-surface antigen 2 (TROP2)-targeting antibody drug conjugate’).

Room without a view

I have now been at the Termeer Center for Targeted Therapies for almost five hours. In that time I have been weighed, had two vials of blood drawn, and the first of three EKG’s taken. I have also peed twice, napped, and met with Dr. Lin, my new oncologist now that I am on trial. Drug was finally released an hour ago but it is frozen and takes three hours to defrost, so infusion will not begin until one. Lots of hurry up and wait.

Last night I was pre-dosed with five 4 mg tabs of dexamethasone as well 360 mg of fexofenadine, both of which will be repeated just prior to infusion. There have been lots of reactions to this experimental therapeutic but fortunately I am entering trial after MTD has been established and they are getting a better handle on how to handle side effects. Also anticipated are some pretty gnarly sounding mouth sores (dime size, painful plaques) which could put a crimp in my dating schedule 😉 I am to prophylactically swish with a steroid mouthwash and have a paste for when they emerge. I have been advised that I shall likely lose weight (those sores) and may lose my hair as well. And there have been some eye issues, so I have been using lubricating drops. Aside from that, fatigue and mild nausea. There is always a price to pay.

On a positive note, some of the side effects of lorlatinib have noticeably receded. My skin—a mess of crusty sores as of late, has begun to clear up and heal (hallelujah). I had to go off of statins because of my elevated liver enzymes and my cholesterol was through the roof last time (high 300’s) but hopefully that shall start to come down as well. The cadence of my speech is speeding up (‘So you’re not going to sound like John Wayne anymore?’ asked one of my friends) and I am already feeling more like me: Linnea pre lorlatinib. Less rage-y, more clearheaded. I like it.

So consider this installment one. More to come post infusion.


Washout: the reality

Getting into a clinical trial is multi step process. First you have to identify an appropriate trial, but I am fortunate to have an oncologist like Alice Shaw, who does that work for me.

After signing the consent form, the real pins and needles part starts, as I now must qualify for the trial.

I’m a match on paper for phase I of DS-1062 but before being formally accepted in the trial there are numerous hoops I must jump through.

On Tuesday of this past week I had an EKG, labs, CT scan of head, chest and abdomen, and an echocardiogram. All in one day. All billed to my insurance. My brother John and sister Bink were flying in from Colorado for a quick visit and they met me at the hospital. As I had another exam the following morning (eyes), we decided to spend the night in Boston. Peter joined us for dinner and one heck of a festive evening.

The following morning I woke up at exactly the time I was supposed to begin my eye exam. Oy vey, someone (me) thought they were setting their alarm but did not. I made some quick phone calls, hopped in the shower, and ubered over. Crisis averted.

However I got a call from one of the research nurses as I was getting ready–my liver enzymes were still slightly elevated and unless they came down, I would not qualify for the trial.

Damn. I was advised to hydrate heavily and more labs were scheduled for this morning. Unfortunately, I am still above normal (likely as a side effect of the pemetrexed) and so on Monday morning I need to get to the hospital at 7 am for IV fluids. Labs will then be drawn again and if my ALT and AST are within range, I will go ahead with the lung biopsy and have my first infusion for the trial on Tuesday. If not, everything will be pushed back a week.

In the meantime I am washing out of lorlatinib. Lots going on chemically in my body right now.

The trial requires a lot of premedication–for nausea, mouth sores and dry eyes. Yesterday I went to pick up my scrips but initially left without them.

As of January one I no longer have a steady source of income as my alimony has ended. This means I qualify for Mass Health, which is a good thing as medical bills have been a huge financial burden. When I went through the drive through at the pharmacy, I was told I needed to come inside to update my insurance information. I did, and then had to stand in yet another line to pick up my meds. However, the cashier told me that it indicated that my scrips needed to be billed to something called Argus before they could go through Mass Health. If I wanted them then I would need to pay cash (five different scrips). I calmly explained to her that I could not afford to do that and that if I didn’t have my prep medications, I couldn’t start the trial on Tuesday. She told me there was nothing she could do and that I would need to call Mass Health.

My brother and sister were waiting outside in the car and I was in tears when I joined them. We drove to the grocery store and while they shopped I waited on hold for customer service at Mass Health. When I finally got through I was told I needed to go back to the pharmacy for a list of my meds and that if I called back in the morning, an investigation into why Mass Health wasn’t showing up as my primary carrier would open. An investigation that could take days.

Now I was really crying. We drove back to the pharmacy, my siblings went inside to get the list but they wouldn’t give it to them. My brother said ‘She’s crying in the car, do you want to go talk to her?’ I was so humiliated by this point but I went back in with my ID. And then we had to stand in another line, and my sister paid cash for my drugs. There is very little humanity in this process at times.

I dropped John and Bink off at the airport this morning. I have spent most of the day close to tears, between the financial stress and anxiety as to whether or not I will qualify for the trial.

This girl is freaking tough but yesterday was the straw that almost broke the camel’s back. I get so tired of complications. Having a limited income sucks. Having terminal cancer sucks. Having some support and assistance—my siblings—was phenomenal. My friend Diane is now across the street and will drive me to my biopsy on Monday. Melinda has leapt into action trying to straighten out the Mass Health mess.

I’m chugging water and willing my liver enzymes down, while wistfully thinking about warm beaches and cold drinks garnished with paper umbrellas.

Dream on.