What Are Lung Cancer Clinical Trials?

Lung cancer clinical trials are research studies that look for new and better ways to treat, detect, or improve quality of life with lung cancer at all stages of the disease.

For a treatment to be approved by the Food and Drug Administration (FDA) for the general public, it must go through three phases of clinical trials. This is the case with nearly every treatment currently available.

This article looks at how clinical trials work, how to find a clinical trial for your cancer, and some of the pros and cons associated with these studies.

What Are Clinical Trials?

Clinical trials are research studies that are designed to test the effectiveness and safety of new treatments and combinations of treatments. They are conducted by a research team that includes physicians and other healthcare professionals (usually in a cancer center or clinic) with patient volunteers who are referred to as "participants."

The experimental drug or treatment (surgery, radiation, etc.) may be new or may involve new combinations of treatments already available.

As of early 2021, there were 2,250 active lung cancer clinical trials registered at ClinicalTrials.gov, with further trials available at some cancer centers.

Interventions

A few examples of treatments being studied include:

• Immunotherapy drugs (drugs that use the immune system or principles of the immune system to fight cancer) such as checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapy
• Targeted therapies (drugs that target specific receptors or pathways needed for cancer to grow) such as EGFR inhibitors
• Monoclonal antibodies, including those that keep cancer from forming new blood vessels (angiogenesis)
• Chemotherapy drugs
• A combination of chemotherapy and immunotherapy
• Newer, less invasive surgical techniques
• Specialized radiation techniques, such as stereotactic body radiotherapy

Research Team

A clinical study is led by a physician referred to as the principal investigator. Other members of the research team include additional physicians, nurses, social workers, and others, depending on the specific trial.

Sponsors

Clinical studies may be sponsored by the National Institutes of Health (NIH), larger cancer centers, pharmaceutical companies, the Department of Defense (DOD), one of the lung cancer non-profit organizations, or other providers and organizations.

Eligibility

Every clinical trial has specific guidelines on people who may or may not participate in the study. Guidelines have inclusion criteria, or the cohort of people being evaluated (for example, a study could be looking only at women), and exclusion criteria, or reasons a person would not be considered a good candidate for the study.

Some factors that may be considered for eligibility include:

• Age (for example, a study may focus on only young adults or only older adults)
• Sex
• The type of lung cancer (non-small cell lung cancer or small cell lung cancer)
• The stage of the cancer
• Tumor mutation status (if the tumor has genetic changes such as an EGFR mutation, ALK rearrangement, etc.)
• In metastatic lung cancer, the location of metastases, such as whether or not a person has brain metastases
• Previous treatments for lung cancer
• Other medical conditions
• General health
• Performance status, or how well a person can perform activities of daily living
  

Location

Clinical trials for lung cancer can be found throughout the world. In the U.S., some clinical trials may be offered at cancer centers in many regions around the country. Others, especially phase I trials, may be offered only at one or a few locations.

Safety

Clinical trials are carefully conducted and monitored to ensure safety. Before beginning a clinical trial, people are required to sign an informed consent form stating that they understand the purpose and potential risks of the study.

An IRB (institutional review board) made up of doctors, researchers, and the general public approves and monitors the study.

How Clinical Trials Work

Clinical trials are not the first studies of a treatment but are the first involving human volunteers. Often there have been many years of preclinical research in the lab and animal studies.

Protocol

Every clinical trial has a protocol, or blueprint, that describes the trial and how it will be conducted. This protocol includes information such as:

• The purpose of the clinical trial
• The eligibility criteria
• The number of people in the trial
• The starting point and endpoint of the trial
• The medication, radiation, or surgical treatment that will be used, including timing, method of administration, and dosage
• Laboratory tests and imaging studies that will be used to monitor people in the trial and how often these will be done
• Length of the trial
• Information that will be gathered
• Endpoint (the outcome that is being measured, such as an increase in survival, reduction in symptoms, etc.)

Phases

There are three major phases of clinical trials although there can be some overlap. For example, some trials combine a few phases to create a phase I/II trial or a phase II/III trial.

While each phase has a primary purpose, information about other aspects of treatment may be gleaned at any stage. The phases are:

• Phase I: Phase I trials test the safety of a new treatment. They also evaluate the delivery method (if a medication will be given orally or intravenously) and dose. Numbers vary, but they commonly include only 15 to 30 people. A Phase I trial may take several years to be completed.
  
• Phase II: Phase II trials look at effectiveness of a treatment against lung cancer. These studies also gather information about side effects and further examine the safety of the treatment. There are usually 30 to 100 people who take part in these studies and they can last several months up to two years.
• Phase III: Phase III studies are designed to answer the question, is the treatment better than the current best available treatment (referred to as "the standard of care.") These studies can include from 100 to thousands of participants and may last a year to four years or beyond.
  

FDA Approval

After all phases of a clinical trial are completed, the FDA then looks at the data found to determine if approval will be granted.

In some cases, especially with lung cancer, an accelerated approval may be given. This may occur when there is a new treatment is found to be effective in a setting where little was previously available. Terms that describe this can include fast track, breakthrough therapy, accelerated approval, and priority review.

Phase IV

Phase IV trials are done after FDA approval and are often referred to as "post-marketing surveillance." Further information is gained as the treatment is used more widely. A phase IV trial may also study a known treatment but with different cancer.

Randomization

In some phase II and all phase III trials people are randomly assigned into either an investigational group (that receive the new treatment) or the control group (that receive the standard of care treatment). This is done to reduce bias in the study.

Crossover

Some clinical trials allow people to crossover (for someone in the investigational group to move to the control group, or vice versa). This may occur if the new treatment does not appear to be working as well as would be expected with the standard treatment.

At other times, the new treatment may be found to be much better than the standard treatment, and a participant may be allowed to switch to the new treatment instead of staying in the control group.

Blinding

To further reduce bias, a study may be blinded. In a single-blinded study, the participant does not know which group they are in. In a double-blinded study, neither the participant nor the investigator knows which treatment a person is receiving.

Cost and Payment

With many trials, the sponsoring organization covers the cost of the treatment. Some trials may include transportation, parking, and more.

Monitoring tests such as labs and imaging studies are often covered by the participant's insurance company, though out-of-network coverage (care or services provided outside your insurer's network) varies.

The Affordable Care Act (ACA) requires insurance companies to cover routine cancer care costs for those taking part in a clinical trial. “Routine costs” are those that anyone who is getting treated for your kind of cancer would have covered.

Insurers are not allowed to drop or limit coverage because a person chooses to take part in a clinical trial. This applies to all clinical trials unless the insurance plan is “grandfathered" (was in effect before the ACA was enacted in 2010).

Pros/Cons

There are both pros and cons to consider before participating in a clinical trial, and it's important to weigh these based on your own desires.

Pros

Points in favor include:

• The new drug or treatment may be more effective or have fewer side effects than the standard of care treatment.
• Monitoring and contact with the health team is usually more thorough.
• Trials can be empowering you, and help you feel like you're in the driver's seat managing your cancer.
• Research may benefit other patients in the future.

Cons

Considerations against joining a clinical trial include:

• The treatment may be less effective or have more side effects than a standard of care treatment.
• Since the treatment is new, it may have serious side effects that aren't anticipated.
• More frequent monitoring means more frequent visits.
• Travel may be necessary.
• Insurance may not cover all labs or imaging studies.

Making Decisions

After reviewing some of the pros and cons of a particular trial, it's important to talk to the primary investigator or research team about any questions or concerns you have.

How to Apply for a Clinical Trial for Lung Cancer

Once you have found a clinical trial you are interested in, it's time to apply to participate. This can be an anxious time for many. It's important to ask every question you have.

The first step is to contact the principal investigator. The contact information is listed at the top of the trial information and often includes the preferred method of contact, whether by phone, email, or an online application form.

Most people do not need to talk to the primary investigator at this point and may speak with anyone on the research team. Some trials have a trial coordinator you can ask to speak with. You (or your doctor) can discuss the trial, see if you meet eligibility criteria, and learn the next steps.

Before beginning the trial, you will need to review the protocol with the research team, discuss any challenges, and complete an informed consent form.

How to Find Clinical Trials

The first step in looking for a clinical trial is to talk to your doctor. They may know of trials that are available (or may even bring it up).

If not, there are a number of options. Unfortunately, there is not a single database that includes every clinical trial, so checking a few resources is a good idea.

Before you begin, gather your medical information so that you can quickly check eligibility criteria as you go through trials. Don't be alarmed if the first several trials do not fit your situation. There are many available.

The trial will show you if it is actively recruiting, has not yet begun to recruit, or has been completed. Some clinical trials are by invitation only. Some options for lung cancer include:

ClinicalTrials.gov

Clinicaltrials.gov is the most comprehensive of databases. It allows you to search by tumor type and more.

EmergMed Matching Service

EmergingMed is a clinical trial matching service that has partnered with the lung cancer organization LUNGevity to create this database. People can search on the database themselves or receive free assistance from a clinical trial navigator in searching for trials. The number is answered during regular working hours at 877-769-4834,

National Institutes of Health

Cancer Clinical Trials at the National Institutes of Health Clinical Center are unique in a few ways. In some cases they allow people to be the very first to receive novel treatments.

But another advantage is that once you have been accepted to participate in a clinical trial, your care is free. This includes the treatment, monitoring tests, follow-up, as well as travel expenses and lodging for those who must travel.

Lung Map (Stage 4 Non-Small Cell Lung Cancer)

Lung Cancer Master Protocol (Lung-MAP) is a collaboration of many research centers that works to match people with advanced non-small cell lung cancer with new drugs being developed to treat stage 4 disease.

National Cancer Institute

The NCI database includes National Cancer Institute supported clinical trials for lung cancer.

Major Cancer Centers

A number of the larger cancer centers also offer databases of lung cancer clinical trials offered at their institution. Just a few examples include:

• Mayo Clinic Lung Cancer Program
• Memorial Sloan Kettering Cancer Center lung cancer clinical trials
• Stanford Medicine lung cancer clinical trials

My Cancer Genome

For people who have advanced non-small cell lung cancer, MyCancerGenome lists clinical trials based on mutation type.

Summary

Clinical trials for lung cancer offer an opportunity to receive treatments before they are approved for the general public. With a carefully designed protocol, investigators and research teams guide people through the three stages of trials. When a treatment is found effective, it is considered for FDA approval.

There are pros and cons to clinical trials, and each person with cancer must weigh these against their own expectations and needs.

Finding a clinical trial can be a bit intimidating at first, but with the help of matching services and support from the lung cancer community and lung cancer organizations, people are finding eligible trials and beginning these new treatments every day.

A Word From Verywell

Lung cancer treatment has changed dramatically in recent years, with many of today's most effective treatments being unheard of a decade ago. Phase I trials that were once thought of as "last ditch" trials are now becoming a mainstay for some people. They frequently offer a chance for survival or prolonged survival that was unheard of before.

The flip side of this change is that it can be overwhelming to seek out and look at options for treatment. Fortunately, there is an amazing and deep lung cancer community online ready to welcome new survivors with caring support and to share what they have learned.