HPV Cancer Resources

Helpful Information for Parents, Patients, Partners, and Providers

Helpful Information for Parents, Patients, Partners, and Providers

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A Brief Guide to Clinical Trials

There are a number of drugs (and other types of treatments) that are being developed to treat HPV-associated cancers, such as cervical cancer and head and neck cancers. Some of these medicines will be focused on attacking the virus itself, while others are directed against other targets inside your body. The pathway to drug development is long, arduous, and expensive. Pre-clinical laboratory work is done first, where the drug is made and tested in a variety of experiments to see how it functions. If it looks promising, it will next be tested in an animal model of the disease that it is designed to treat. Signs of any toxicity to the animals will be carefully monitored, for if the drug is too toxic, development halts at that stage. If the drug still looks promising, it will need to be tested in humans to determine if it really works and has an acceptable safety profile. This is done through clinical trails. If you want a comprehensive explanation about how clinical trials work, click here. If you want just a brief introduction, keep reading.

Clinical trials are medical studies that are generally done to find new drugs or treatments for any number of diseases, including cancer. They follow a series of steps that are designed to reveal whether or not the new treatment is, or is not, effective. If there are currently no effective treatments for a disease, the clinical trail will be designed to figure out if it brings any benefits to patients. If there are existing drugs or treatments, then clinical trials are done to figure out if the new treatment or drug is better than existing treatments, in which case doctors will then switch over to using the new treatment. When I say that the goal is to determine if the new treatment is better, this can mean a number of different things. It could mean that the drug cures more patients than the previous treatment (usually referred to as the current “standard of care”). Better could also mean that it is only as effective as the standard of care, but it’s advantage is that it has fewer side effects. Some trials are done to determine if a cheaper drug or treatment is equally as good (or better) than the standard of care, because this will save the patient (and/or his or her insurance company) money, and overall more patients are likelier to be treated.

In certain rare circumstances, new drugs and treatments for cancer patients are tested against placebo (i.e. an inert substance that should not have any biological effects on the patient). This might occur in a trial where the standard of care is essentially surveillance of the patient. This circumstance should require an extensive ethical review before it is put in place. You can read more about this in FDA Recommends Use of Placebo Only in Certain Oncology Trials.

To join a clinical trial, patients must meet specific criteria in order to qualify. These criteria are put in place to try to ensure that patients getting the new treatment or drug are somewhat uniform i.e. their disease is at a similar stage. That makes it easier to determine if the new treatment does or does not work. Clinical trials are overseen by an IRB (institutional review board), which are groups of doctors and medical ethicists who’s goal is to make sure the trial is ethically done (doesn’t put patients at undue risk) and that the trial is rigorous enough to provide a clear answer when it is completed as to whether or not the new drug or treatment is superior. You will generally be asked to sign an “informed consent” document before entering a clinical trial. Read that document carefully. It will spell out all the details about the trial, including what is being tested, and the hoped for outcome of the trial.

If you participate in a clinical trial, you will generally be assigned to a particular group for the purposes of comparing one set of people with another group getting a different treatment. The two groups generally consist of one set of patients that get the current treatment (the standard of care), while the other group of patients get the new drug or treatment. There may be multiple groups of patients getting the new treatment, with each of these groups getting a different dose of a new drug to determine which one is the most effective, or has the fewest bad side effects. Patients do NOT get to choose which of these groups that are assigned to, and assignment is generally done on a random basis. Patients joining a clinical trial are not obligated to stay in the trial if they feel it is not helping them, or if they don’t want to deal with the side effects of the new treatment. If you participate in a clinical trial, you can withdraw at any time and for any reason (or for no reason at all).

Any particular clinical trial is generally done at at limited number of hospital or medical centers where they have the resources to oversee the care of the patients in the trial. As trials progress through their different phases (see below) they generally include more patients and more locations. Participating in a trial may require you to travel to a distant location and stay there for a period of time that will be determined by the nature of the treatment. Costs for participating in a clinical trial are usually covered by a drug or medical device company that is supporting the trial, or by the medical institution where it is being done. Getting to the trial location and staying there is generally not covered, but sometimes it is. Always ask your doctors for details if you are concerned about this, or any other aspect of the trial.

One thing to know about clinical trials is that even though patients are selected to have somewhat similar characteristics before entering the trial, they do not generally respond equally well to the drug or treatment. Some patients may have a spectacular response, while others may just be helped a little, and some may derive no benefit from it at all. Some may actually be harmed by the trial treatment. There is no way for the doctors to know in advance how any individual patient will respond. As the trials advance, doctors will try to figure out specifically what is different between the patients who responded well (if there are any) and those who did not. This information can help guide future trials, where doctors may be able to more readily pick out patients who will respond favorably to the new drug or treatment.

Most clinical trials are divided into four stages, referred to as phases, which are described below. Note that the overall success rate for drugs entering clinical trials is only about 10 percent overall (cancer drugs do a bit better). Put another way, 90 percent of drugs that enter clinical trials will never be approved by the FDA for sale and will not be given to patients. The clinical trial process is meant to be a very rigorous process because we don’t want to give people ineffective drugs. On their own they would be worthless, and some might even cause a patient further harm. Using a worthless drug might also keep people from being treated with different medicines that actually are effective.

Here are the four stages of clinical trials:

Phase 1: Screening for safety

These trials usually involve between 20 and 80 healthy volunteers. They will be given the drug one at a time and their responses will be closely monitored. The idea is to determine if the drug is safe, what the most frequent side effects are, and how the drug is metabolized and excreted from the body. Measuring effectiveness is not the goal of phase I trials. IF the drug passes these safety tests, it moves to phase II.

Phase 2: Establishing effectiveness

These trials usually involve between between a few dozen and a few hundred patients. Those running the trial will be trying to find preliminary evidence on whether the drug works in people with a certain disease or condition. These trials are usually done as controlled trials. People getting the drug will be compared to those who are getting either the generally accepted standard of care treatment, or a placebo (an inert pill with no physiological effects). Safety will continue to be evaluated, as well any side effects noted. If the phase 2 trial shows sufficient evidence that the drug or treatment may be useful, and there are not side effects that are considered too serious, then a phase III can begin.

Phase 3: Final confirmation of safety and effectiveness

These usually include a few hundred to many thousands of patients. All the elements of phase 2 are observed here, but with a much larger group of people. The idea is to look for rarer side effects, and to treat enough patients to determine if any benefits achieve what is termed mathematical significance. Different groups of patients may be tested, different doses may be compared, and effectiveness will be measured and compared to those not getting this particular treatment.

If a drug passes the phase 3 hurdle, the drugs sponsor will prepare an application to the FDA to license sale of the drug in the U.S. Licenses will then eventually be sought with regulatory agencies in other countries. The FDA will carefully review the data submitted by the company, and if the information is both complete enough and convincing, the FDA will approve it and it can be sold.

Once drugs get to the marketplace, they may now be used by tens of thousands, or even millions of people. As a result, they enter into a new stage:

Phase 4: Large scale safety monitoring

Rare side effects that didn’t show up may become apparent with these larger numbers of patients. If these do appear, the sponsor may have additional conversations with the FDA regarding whether the drug should stay on the market, or whether or not warnings need to be added to the information patients and doctors get with the drug. Drugs can and do get pulled from the market at this stage.

Clinical trials can offer a maddening dilemma for patients, who may be asked to choose whether they want the standard of care treatment, or to try something new that may, or may not, be better (and could even be worse). This is an important issue to discuss in depth with your doctors, as there is likely to be no right or wrong answer before the trial is started. You will have to weigh the possible advantages and disadvantages and come up with a decision you feel comfortable with. There is no obligation to participate in a clinical trial, and your doctor will not be mad at you if you decline to participate.


How To Find An Appropriate Clinical Trial

Clinical trials are where new drugs and treatments are developed. All clinical trials have very specific requirements for the patients that can enroll in the trial; simply having the disease is not sufficient. Above I’ve posted a brief guide to how clinical trials work. Finding a clinical trial that would be appropriate for you can be challenging. The first step is to ask your doctor, and if your doctor doesn’t know, ask her or him if they know of someone who does. You can search yourself for clinical trials in the US at the official website that’s supposed to cover these, clinical trials.gov. This website can be a bit difficult for lay people to navigate. It is generally up to date, though it is likely to be missing some trials, and the status listed for others (e.g. recruiting or closed) may have changed. These problems are widely acknowledged in the industry, but have been around for years.

To find a clinical trial in the US - Clinicaltrials.gov; the site is run by the US National Library of Medicine

To find a clinical trial in the UK - UK Clinical Trials Gateway, NHS National Institute for Health Research

To find a clinical trial in Australia - Australia Cancer Trials sponsored by the Australian Government

Accessing these can be done at no cost.

As noted above, navigating these websites is not easy, especially for novice users. It would be nice if doctors could simply point you to the best trial for your specific condition, but many have neither the time to do that, nor are they knowledgeable about the thousands of clinical trials that are ongoing and that you might be eligible for. Overall, it’s hard to find patients for many clinical trials, and that’s simply because they are unaware of what is available.

Here’s an article describing the problem: How to Find Clinical Trials for Experimental Cancer Treatments You should also look at An Overview of Cancer Clinical Trial Matching Services to get a general feel for how these services work. Another good place to look for info is at The CISCRP The Center for Info and Study on Clinical Research Participation.

You could try calling the National Cancer Institute, which offers a toll-free phone number, 888-624-1937, that connects patients to a clinical trials referral coordinator.

New companies are entering the field to try to change this dynamic. There are services that you can hire that will navigate their way through this information and point you to a clinical trial that might meet your needs. Some of these are free to the patient (i.e. drug industry or the government will pay for the trial).

EmergingMed Clinical Trial Navigation Service is a private company that was founded in 2000 to accelerate the discovery of new and better treatments for people with serious and life threatening medical conditions. It’s based in Durham, NC. This is a free service for patients. It’s searches run on the OncoLink platform.

Cancer Treatment Navigator is a consulting firm that helps cancer patients find better treatment options that might not have been considered yet based on scientific and clinical data. They charge patients for their services. You can find their FAQ page here. They are located in Seattle, WA.

Expanded Access Navigator: From their website: “Expanded Access (EA) may be considered for patients who have exhausted their treatment options and are not eligible for, or able to participate in, a clinical trial. EA - also known as compassionate use, named-patient use, or single-patient access - provides some patients who have serious or life-threatening diseases or conditions with access to investigational treatments not approved by the U.S. Food and Drug Administration (FDA). The Reagan-Udall Foundation’s Expanded Access Navigator (for the US FDA) provides physicians, patients, and caregivers with guidance on EA and related topics.”

Antidote.me – Matches people with clinical trials. It doesn’t cover all diseases, and as of Oct.. 2018 it did not have any trials for HPV-caused cancers at all. Hopefully these will be added at a later date. The site does not clearly state how the trials on its site came to be there, and why trials not on the site are unavailable through their platform.

Driver is an app that matches cancer patients with clinical trials. You can find their FAQ here. Patients are the ones who pay for this service. For those who can’t afford this, it has a charitable arm (Driver for All). Here’s how it works. Driver has built its own automated machines to analyze patients’ tumor samples, which it gets from the hospital where patients got their initial tumor biopsy. Driver’s machines analyze the genetics and other molecular characteristics of the tumor, and that information is then matched to clinical trials that are ongoing at cancer centers Driver has partnered with. [NOTE: DRIVER HAS SHUT DOWN AS OF MID OCTOBER 2018 (SIX WEEKS AFTER IT LAUNCHED) BECAUSE IT RAN OUT OF MONEY. DETAILS CAN BE FOUND HERE.]

Researchmatch.org is, according to its website, “a free and secure online tool created by academic institutions across the country who want to include you in their mission of helping studies improve health in the future. ResearchMatch works by emailing you about studies that may be a good match for you.”