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Clinical Trial Information - a Primer

lilacbrroller's picture
lilacbrroller
Posts: 412
Joined: Jun 2012

** I posted this on Colon Club and am cross posting it here for everyone's information and benefit Cool

 

In this thread, I’d like to post some information about clinical trials in the US, based on my experience participating (as a lab rat) in two of them! Feel free to add to this.

1. Where to find trials

http://www.clinicaltrials.gov is the official US Government sponsored database for clinical trials. the main portal of this site offers a number of online tutorials to help users locate suitable trials. Other intermediaries offer trial finders as well (others, feel free to post these - I have not used them.)  

2. Where are trials conducted

Trials can be conducted by oncologists everywhere, not just in major cities, universities, or in large hospitals. The “mothership” for US trials is the National Cancer Institute (NCI) which is part of the National Institutes of Health (NIH), a branch of the US Department of Health and Human Services (HHS.) NCI runs trials at headquarters in Maryland and at regional centers across the US. Here is a link to help find just the trials run by NCI:  
http://www.cancer.gov/clinicaltrials

3. Cost

Trials at NCI facilities are completely free - all drugs, scans, doctors visits, surgery, hospitalization, etc, and even travel and lodging are reimbursable.  

Trials at other locations are usually cost shared between the patient (including the insurance provider) and the test facility. Trial drugs/treatments are always free of charge. Certain tests, scans and medical consultations are free, and others are the responsibility of the patient. Best to sort this out in advance. Some insurance policies do not cover costs associated with clinical trials. In some US states, insurance companies are not required to pay portions of clinical trial expenses, so they don’t… best to read your policy for specific coverage first, or contact the company directly to be sure.


4. When to seek out clinical trials

Generally speaking, clinical trials aren’t the first option when diagnosed with cancer. For ethical reasons, doctors usually don’t administer experimental drugs (and other treatments) to patients who have not exhausted other options, on the chance that a proven, approved drug/treatment might be life-saving. But, that being said, it may be possible to participate in some studies as a newbie - it’s best to carefully read the “inclusion” and “exclusion” criteria listed - each trial provides points of contacts, and you can always ask..  

Time is big factor. It’s best to try trials when you’re not too close to “the end.” Depending on the institution, it can be a month or more before you can be admitted to the trial and receive any treatment, due to administrative requirements (registration, scans, screening, meetings with research doctors, etc.) Many require patients to be off of previous chemo for at least 4-6 weeks prior to starting the experimental treatment, in order to “clean” it out of their systems. And some require tests that you may not have had already, like MSI. That also adds time. 

5. How to determine if you qualify for a particular trial

Trial announcements on http://www.clinicaltrials.gov follow the same standard format, and two sections contain general and specific qualification details: “purpose” and “eligibility.” The purpose is at the very beginning of the announcement and discusses which types and stages of cancers are being studied. Further into the announcement is the eligibility section, which in addition to age and gender requirements, contains the “inclusion” and “exclusion” criteria which specify conditions which need to be present, or absent, in order to qualify for the trial. Some are easy to understand, others you might want to run past your oncologist because they are very technical in nature. If you have any questions as to whether you would qualify or not, each trial provides at least two points of contact, so just ask them. 

**Many studies state that participants may not have had chemotherapy or biologic agents within xx weeks before the first dose of study treatment. Don’t worry about this. It doesn’t mean this time must elapse before you are accepted into the trial. It just means that you’d have to stop your current treatment and wait a certain amount of time before actually receiving the experimental treatment. 

6. Suggestions for how to choose a trial

Make a list of all the trials you're interested in. Eliminate any for which you do not meet the criteria. Then consider:

  • side-effects (are they permanent?) or risks?
  • how long will the protocol take?
  • where you need to go (distance) to receive the treatment(s)
  • costs both in $ and time away from family/work
  • reputation of the organization backing the trial
  • whether it's potentially curative or not
  • how likely is the hoped-for outcome
  • are you healthy enough NOW to withstand the protocol
  • have you got anything to lose? anything to gain?
  • will participating in this trial preclude you from a future treatment you might want to try if this one doesn't work?


7. Phases Explained

Clinical trials to test new cancer treatments involve a series of steps, called phases. If a new treatment is successful in one phase, it will proceed to further testing in the next phase. During the early phases (phases 1 and 2), researchers figure out whether a new treatment is safe, what its side effects are, and the best dose of the new treatment. They also make sure that the treatment has some benefit, such as slowing tumor growth. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid.

There are also very early (phase 0) and later (phase 4) phase clinical trials. These trials are less common. Phase 0 trials are very small trials that help researchers decide if a new agent should be tested in a phase 1 trial and submitted for FDA approval. Phase 4 trials look at long-term safety and effectiveness and take place after a new treatment has been FDA approved and is on the market.

Each trial will state up-front which phase it is, usually in the “purpose” section. 


Phase 1 - Is the treatment safe?

       

 

      The goal is to find out if the treatment has some effect, how it is metabolized, what the most frequent and serious side effects are, how the new treatment should be given (by mouth, in a vein), and to determine a safe dose.

Phase 2 - Does the treatment work? 

      Drugs/treatments (and safety) are studied further in a larger pool of participants to determine effectiveness. Specific cancers are often targeted.

Phase 3 - Is the new treatment better?

    If a treatment does show results in earlier phases, in this phase it is compared with the current standard treatment(s) to demonstrate if it is better or, perhaps is equivalent but with fewer adverse side effects. 


8. Randomization, Placebos Explained

Placebos: Placebos are NOT ALWAYS GIVEN!!!! This is a common misunderstanding. Each trial will state clearly if placebos (sugar pill) are given, usually up front. If a trial does not mention placebo anywhere in the description, placebos are not given. Period!  

Some trials compare a new drug to a placebo. If your cancer is fairly stable and you have a few years to live, it might be worth the risk to try this, if you can afford to potentially go without treatment for 3-6 months if you are given the placebo. 

Some trials test cocktails, so you’d receive an approved drug (like Stivarga/Regorafenib) plus either a new drug or a placebo. On the positive side, if due to your insurance situation your out-of-pocket chemo costs are astronomical, this option enables you to obtain standard treatment for free, and potentially a new drug. 

Randomization: Each trial will state up-front whether it is randomized or not. Phase 3 trials are nearly all randomized, and Phase 2s can be but usually are not.  Randomization and placebo are not the same thing - Most of the time phase 3 trials compare standard drugs against new drugs, randomized, with NO placebo at all. 

When new drugs are compared to standard treatment, like erbitux and 5-FU , or a placebo, selection is randomized in order to avoid bias. Bias occurs when a trial's results are affected by human choices or other factors not related to the treatment being tested. For example, if doctors could choose which patients to assign to which groups, some might assign healthier patients to the treatment group and sicker patients to the control group, without meaning to. This might affect trial results. Randomization helps ensure that this does not happen.

In the simplest trial design, one group receives the new treatment. This is the investigational group. The other group receives standard therapy. This is the control group. At several points during and at the end of the clinical trial, researchers compare the groups to see which treatment is more effective or has fewer side effects. A computer is usually used to assign patients to groups.

• Single-blinded trials are those in which you do not know which group you are in and which intervention you are receiving until the trial is over.
• Double-blinded trials are those in which neither you nor the investigators know which group you are in until the end of the trial.

If you are really seeking a new drug, it is risky to choose a randomized study, and you may not qualify anyway if you’ve already had the standard treatment it is being compared to (if a phase 3 study). If this is the case, keep searching the database: frequently there can be more than one study for the same drug, each slightly different, or, several drug companies might be developing similar products, such as the PD-1 inhibitors, and some of the other drugs’ studies may not be randomized. 

9. How to apply, and what is it is like to be in a trial?

Applying is simply contacting the trial points of contact, and submitting information they ask for. Typically they’ll want discs of your most recent scans, bloodwork, and doctor’s notes. Some of the info you’ll provide, and some your oncologist/doctor will need to submit. Definitely read through the inclusion and exclusion criteria first, and don’t waste your time on trials which you clearly do not qualify for; there is not room for much negotiation as the studies have specific parameters. Don’t make assumptions as to your disqualification either; if something isn’t listed as exclusion criteria, chances are it isn’t one for that particular trial. When in doubt, talk to your oncologist or contact the trial directly. 

Each trial is led by a Principal Investigator (PI) who is usually a medical doctor or PhD. Often, he or she is listed as a point of contact in the trial, along with an assistant. Depending on the institution and the scale of the trial, the PI may have several levels of assistants and associates whom you may deal with during participation. You may interact with the PI at every appointment, or very rarely, depending on the study.  

You will be required to read and agree to an informed consent statement, which will explain to you the risks and potential hazards of receiving the trial treatments, and your rights as a patient, including the right to withdraw at any time. The informed consent may also cover the institution’s rights to use your body products (blood, tissue samples, etc) during and after the study, as well as if you want to be contacted after the study has been completed. 

Participating in a trial is not much different than seeing an oncologist and having a regular chemo appointment, however the length of time you can participate in the study and receive treatment often is determined by your progress against pre-set benchmarks. Each study is different. My NCI experience has been over the top because groups of people in white lab coats would randomly come in and chat with me, but otherwise, it’s been business as usual for both trials I’ve been in. Both trial experiences were very positive for me, even though I was booted out of the first trial for lack of results; the care I received was outstanding, and the research doctors and nurses were very professional.

jen2012
Posts: 1607
Joined: Aug 2012

Karin...thanks so much for this.  It is very helpful and answers some questions I've had.   I'm going to save it to my computer so I don't lose track of the info.

i hope things are going well for you.

janderson1964
Posts: 2215
Joined: Oct 2011

Thanks Karen. How are you doing on your current trial.

lilacbrroller's picture
lilacbrroller
Posts: 412
Joined: Jun 2012

Thanks. No treatment yet.  I am still waiting for certain tests to be completed on the trial.  They harvested my tumor, chopped it up into itty bitty pieces, DNA sequenced it to find mutations, found active TILs and grew some of them, and then sent out the tumor bits I think to isolate mutations and grow chunks of tumor expressing only that mutation.  That's where i"m fuzzy but they sent that bit out and are waiting for final results, which should come in this week.  Next step is to release the TILs to hopefully attack the mutated tumor bits.  I thought that's what they were doing already but I was mistaken. So hopefully by next week, they'll know a) if my TILs do attack the tumors, and b) which mutations are attacked the most.  Final step is to grow the ones that do the most attacking... And that's all I know. 

I"m hoping to have an answer go or no-go next week. Oh and they have do a final physical to make sure I'm still in good health. Touch wood I still am...

Lots of waiting. I've been off chemo since January, so four months with no chemo. My CEA is up but not at crazy levels, I'm still breathing and walking around. All good.  All in all it will be five months since I applied.  Yikes.

cheers

Karin

janderson1964
Posts: 2215
Joined: Oct 2011

Thanks for the detailed updat. I am glad you are still feeling well and am really, REALLY hoping this works for you.

herdizziness's picture
herdizziness
Posts: 3642
Joined: Apr 2010

2015-04-19 Thanks for the info.  I'm anxiously waiting to see how this trial works for you and hoping it works fantastic in your case.  Thank you for the update and keep us informed on how it's going, ok?

Thinking of you and wishing the best,

Winter Marie

Cazz
Posts: 107
Joined: Mar 2015

Hi Karin, which trial are you waiting for?  Is it one of the NCI/NIH immunotherapy ones in Bethesda?  I have applied there and the tumor chopping up and the TILs sound like one of the ones I am trying to get into.  I am scared to hear that it has been five months since you applied though as I first applied six weeks ago and only yesterday did they finally say that they had everything they needed (blood, tumor tissue, reports) and they would now spend 2 - 3 weeks reviewing them.  I have not had any treatment since my initial chemo/radiation that ended in October last year.  The chemo didn't work and I have been trying to find alternatives, but am getting very worried as I have now developed a second liver met, some affected lymph nodes and gained a met in my leg (of all places) and goodness knows what else is growing and where.  I can't wait another two or three months for them to get round to starting treatment.  I have an appointment in early May at MD Anderson, but the only trial I would want is not yet active.  There is another promising one but they are doing a randomized trial - half get the new stuff, the other half gets just standard treatment, which my oncologist agrees is unlikely to work.  As you don't know which you would get, I can't take the chance of wasting another 3 to 6 months.

How long is it since your initial appointment, and then how long did you have to wait for them to harvest your tumor, and how long ago was that?  Roughly, of course, I don't expect exact hours or minutes!  But I would like a feel for the time frame so that I can make a better decision if MD Anderson offers me something that I am not happy with whether to take it or hold out for a different option at NCI, which might be a bit of a gamble.  Thanks for your help.

Carol

Trubrit's picture
Trubrit
Posts: 5378
Joined: Jan 2013

My friend's husband has been on a couple of trials. He has inoperable Kidney Cancer. The last trials side effects were horrendous. I would read her emails and weep for the both of them. And then, her last email, since the trial has ended, NED. 

I admire those willing to go on trials, even as a life saver. Its a life saver for everyone who comes after. So I thank you. 

You are one strong woman. 

Sue - Trubrit

lilacbrroller's picture
lilacbrroller
Posts: 412
Joined: Jun 2012

HI, all. Thanks for the well wishes.  Glad your friend (TB) is NED after his trial. 

Cazz - I've posted a separate thread on this board about my experiences with this trial, but FYI here is a link to the study: <URL>https://www.clinicaltrials.gov/ct2/show/NCT01174121</URL>. Is is the same one you've applied for? 

You've only grown two small mets since October,? you're in great shape!  It's been four months since I applied - December before Christmas. I didn't have the surgery to remove the tumors til February 10th. So that was two months.. but, I applied before Christmas and nothing happened til the holidays were over. And I had booked a two-week vacation in January, so that delayed things as well. It's a long wait regardless. My last trial I waited a month, I think, before receiving treatment while waiting for admin stuff like insurance approvals and appointments.  

There is also a thread on colon club dedicated to this trial - two of us are in the trial and several people have applied.  If you pick another trial, you can always follow others' experiences in that thread and see how we do before jumping in yourself!!  Tongue Out

 

cheers

Karin

Cazz
Posts: 107
Joined: Mar 2015

Thanks for the link.  The trial is identical to one I have applied for except that mine is looking for patients with metastatic anal cancer caused by the HPV virus, which I have.  Steven Rosenberg is the principal investigator for both so I guess they just want to keep the types of cancer separate in case it works better against one than the other.  I will try and find the thread on your trials so I can follow along and cheer for you guys, hoping that I am just a few weeks behind you.  Maybe when we are declared NED for five years we can all meet up and toast Dr Rosenberg with the finest champagne - and I'll even buy!  HSE (hope springs eternal)

It seems like a long time to me since having your tumor removed on February 10th and they still haven't told you whether they will treat you, but I think I will just have to learn some patience.  Thanks for saying that you think I'm okay with "only" having a couple of new mets, it helps me put things in perspective.

Love your lilac breasted roller.  I had to look him up and as he is native to sub-saharan Africa I would guess he's not nesting in your back yard!

lilacbrroller's picture
lilacbrroller
Posts: 412
Joined: Jun 2012

Definitely let's toast if that happens. Good luck getting in.  I wonder how many of these studies Dr. R is running? I don't remember seeing the one you are in.  

perspective is good. My Russian friend says that when the glass is half empty, there is more room for vodka. 

lbr is a beautiful bird, but yes, I live in the US on the East Coast. The brightest birds we have are robins and blue jays, and little yellow finches. 

atb

Karin

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