Clinical trials and colorectal cancer

Clinical trials are research studies that help doctors learn whether a new treatment, a new combination of treatments, or a new way of using an existing treatment is safe and effective.

You may want to talk with your doctor about clinical trials as part of your treatment plan. A clinical trial may be available before treatment begins, after a first treatment stops working, or after several treatments have already been tried.

Finding a clinical trial can feel intimidating, but you do not have to search alone. The Colorectal Cancer Alliance can help you explore possible options and prepare a list of studies to discuss with your doctor.

Connect with the Cancer Care team

Types of clinical trials

Clinical trials are designed to answer different questions about cancer prevention, diagnosis, treatment, and quality of life.

Most cancer clinical trials are treatment or intervention trials involving people who have cancer.
These studies may evaluate:
- New medicines
- New combinations of treatments
- Immunotherapy
- Targeted therapy
- Cancer vaccines
- New approaches to surgery or radiation
- New ways of using existing treatments
Researchers may study whether a treatment is safe, controls cancer, helps people live longer, causes fewer side effects, improves quality of life, or helps prevent cancer from returning.
These trials study ways to improve comfort and quality of life for people with cancer and their caregivers.
They may evaluate:
- Treatments for physical symptoms or side effects
- Nutrition and physical activity interventions
- Emotional and mental health support
- Support groups or one-on-one counseling
- Strategies to help caregivers cope with the demands of cancer care
Supportive and palliative care may be provided at any stage of cancer and can be given alongside cancer treatment.
Prevention trials study ways to reduce the risk of developing cancer or prevent a new cancer from developing.
Participants may include:
- People who have not had cancer
- People with an increased cancer risk
- Cancer survivors who may have an increased risk of developing another cancer
These studies may evaluate medicines, nutrition, physical activity, screening behaviors, or other risk-reduction strategies.
Screening trials study methods of finding cancer earlier, when it may be easier to treat.
Researchers may evaluate:
- New screening tests
- New ways to use existing tests
- How often screening should occur
- Which groups may benefit most from a particular screening method

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Clinical trials can be an option at every step of treatment

A clinical trial is not always a “last resort.”

Some trials are specifically designed for people who have not received treatment for advanced or metastatic colorectal cancer. Other trials are designed for people whose cancer has grown after one or more treatments.

Because eligibility requirements and available studies can change throughout your care, it is helpful to ask about clinical trials early — and ask again before each major treatment decision.

Ask early. Ask again.

Clinical trial options can change based on your treatment history, biomarkers, overall health, location, and which studies are currently enrolling.

What does “line of treatment” mean?

A line of treatment describes the order in which treatments are used.

First-line treatment

First-line treatment is the first treatment or treatment plan used for a person’s cancer.

Depending on the cancer’s stage, location, and biomarkers, first-line treatment may include:

Chemotherapy
Immunotherapy
Targeted therapy
Surgery
Radiation
A combination of treatments

Second-line treatment

Second-line treatment may be considered if the first treatment:

Does not control the cancer
Stops working
Causes side effects that are too difficult to manage

Later-line treatment

Later-line treatment generally refers to third-line, fourth-line, or subsequent treatment. These options are considered after a person has already received two or more previous treatment approaches.

Clinical trials may be available in any of these settings. Some studies are open only to people starting their first treatment, while others require participants to have received specific treatments previously.

Clinical trial treatment lines

A first-line clinical trial may be an option for someone who is newly diagnosed with advanced or metastatic colorectal cancer or is beginning cancer treatment that has spread.
These studies may compare a new treatment approach with the current standard of care.
A first-line trial might evaluate:
- A new combination of chemotherapy and targeted therapy
- Immunotherapy for people with certain biomarkers
- A targeted treatment for a tumor with a specific gene change
- A treatment plan based on the location or biology of the tumor
- A treatment approach guided by circulating tumor DNA, also called ctDNA
For metastatic colorectal cancer, treatment and clinical-trial options may be influenced by tumor characteristics such as:
- MSI or mismatch repair status
- KRAS or NRAS mutations
- BRAF mutations
- HER2 status
- Other actionable tumor changes
- Whether the original tumor began on the left or right side of the colon
Biomarker testing can help your care team identify standard treatments and clinical trials that may be appropriate for you.
What to remember: Asking about clinical trials before starting treatment can help you understand all available options, including studies that may no longer be available after treatment begins.
Learning that a treatment is no longer controlling the cancer can be difficult. It is also a common point at which doctors discuss additional treatment options.
Second-line clinical trials may study:
- A new medicine after standard chemotherapy
- A targeted treatment for a specific tumor mutation
- A new immunotherapy combination
- A different way of combining existing treatments
- A treatment for people who have already received a particular chemotherapy or targeted therapy
Some studies require participants to have received a specific previous treatment. Other studies may exclude people who have already received certain medicines.
Your complete treatment history is therefore important when determining whether a clinical trial may be a match.
What to remember: If your cancer grows after first-line treatment, it does not mean you are out of options. Ask whether a clinical trial matches your cancer type, biomarkers, health, and treatment history.
Later-line clinical trials are often designed for people who have already tried multiple treatments.
They may be especially relevant when:
- The cancer has become resistant to standard treatments
- Standard treatments have caused difficult side effects
- Biomarker or genomic testing has identified a tumor feature that may be targeted
- A patient has limited remaining standard treatment options
Later-line studies may include:
New targeted therapies
Treatments designed to attack specific mutations, proteins, or other changes in cancer cells while limiting damage to healthy cells.
Immunotherapy combinations
Studies testing whether two immune-based treatments—or immunotherapy combined with another treatment—can help the immune system recognize and attack cancer more effectively.
Cancer vaccines
Investigational treatments designed to teach the immune system to recognize cancer-related markers and respond against cancer cells.
Cell therapies
Investigational treatments that collect, select, or modify immune cells so they can better recognize and attack cancer cells.
Antibody-drug conjugates
Targeted treatments that connect an antibody with a cancer-killing drug. The antibody helps carry the drug to cells with a particular target.
Treatments matched through genomic testing
Studies that use genetic information from a person’s tumor to match the person with a treatment designed to target the cancer’s specific features.
Approved treatments studied in new ways
Some clinical trials evaluate an FDA-approved treatment in a new cancer type, treatment combination, dose, or treatment setting.
What to remember: Even if you have already received several treatments, a clinical trial may still be worth discussing — especially if you have had comprehensive biomarker or genomic testing.

How biomarkers may help guide treatment and clinical-trial options

Biomarkers are characteristics of a cancer that can provide information about how the cancer may behave or respond to treatment.

Research has led to biomarker-matched treatments for some people with advanced colorectal cancer. Examples include treatments directed at:

MSI-H or dMMR tumors
Certain KRAS mutations
BRAF mutations
HER2-positive tumors
NTRK gene fusions
Other uncommon tumor changes

Some biomarker-matched treatments are FDA-approved for patients who meet specific requirements. Others remain investigational and are available only through clinical trials.

A treatment being approved or studied does not mean it is appropriate for every patient. Ask your doctor:

Whether your tumor has received recommended biomarker testing
Whether additional testing may be helpful
Whether a treatment is approved for your situation
Whether previous treatments are required
Whether an appropriate clinical trial is enrolling

Learn more about why biomarkers matter

What is a basket trial?

Most clinical trials focus on one particular type of cancer. Some studies, however, enroll participants primarily based on a tumor biomarker rather than the part of the body where the cancer began. These studies are sometimes called basket trials.

For example, a basket trial may study the same targeted treatment in people with different cancer types whose tumors share a particular genetic change.

Basket trials may provide additional opportunities for people whose tumors have uncommon biomarkers.

Clinical trial phases: what patients should know

Clinical trials are commonly grouped into phases. Each phase is designed to answer different research questions.

Phase 1

Phase 1 trials primarily study safety, side effects, the appropriate dose, and how and when a treatment should be given.

These trials generally include a relatively small number of participants.

Phase 2

Phase 2 trials look more closely at whether a treatment appears to work for a particular cancer or group of patients while continuing to evaluate safety.

Phase 3

Phase 3 trials usually compare a new treatment or treatment approach with the current standard treatment.

These studies often include a larger number of participants and may provide evidence used to support FDA approval.

Phase 4

Phase 4 studies take place after a treatment has been approved. They help researchers learn more about the treatment’s long-term effectiveness, safety, and use in broader groups of people.

The phase of a trial does not tell you whether the study is right for you. Ask the research team about the purpose of the study, what is already known about the treatment, and what researchers are still trying to learn.

Will I receive a placebo?

Many people worry that joining a cancer clinical trial means they may receive no treatment.

When an effective standard cancer treatment exists, a placebo is rarely used by itself. More commonly, researchers may compare:

A standard treatment with a new treatment
Standard treatment plus a placebo with standard treatment plus the study treatment
Two active treatment approaches

Before you agree to participate, the research team must explain:

Which treatments are being compared
How participants are assigned to a treatment group
Whether a placebo is involved
What care you would receive in each group
What treatment options are available outside the study

Why timing matters

Every clinical trial has eligibility requirements. These rules help protect participants and allow researchers to answer specific scientific questions.

A study may require that you:

Have received no previous treatment for metastatic disease
Have already received a particular treatment
Have a specific biomarker
Have cancer that can be measured on scans
Meet certain health and laboratory requirements
Have not previously received a certain medicine

Because of these requirements, you may qualify for a study at one point in treatment but not at another.

Before starting a new treatment, ask your doctor whether that treatment could affect your eligibility for a clinical trial now or in the future.

Questions to ask yourself

Before you join a clinical trial, there are some things to consider. Ask yourself the following:

Why do I want to participate?
Do I understand the purpose of the study?
Am I willing to participate if I do not receive the study treatment?
Am I comfortable participating even if the study may not benefit me personally?
Do I understand the possible risks and benefits?
Do I understand that I can leave the study at any time?
Do I have the time and resources required to participate?
How might travel, childcare, work, or other responsibilities affect my participation?
Do I have the support I may need during the study?

Questions to ask your doctor or the research team

Consider asking:

About your options

Are there any clinical trials I should consider before starting this treatment?
What line of treatment am I in right now?
Is this a first-line, second-line, or later-line study?
Has my tumor received all recommended biomarker or genomic testing?
Do my biomarkers help match me with any clinical trials?
What treatment would I receive if I do not join the study?
Could joining this study affect my future treatment options?
Could starting another treatment affect my eligibility for this study?

About the study

What is the purpose of the study?
What treatments are being compared?
How will my treatment be selected?
Is a placebo involved?
What medicines, procedures, tests, or scans will I receive?
How does the care in the study compare with the care I would receive outside it?
Can I continue taking my regular medicines?
Where will I receive care?
Who will be responsible for my care?

About risks, benefits, and logistics

What are the possible benefits?
What are the possible short-term and long-term risks?
What side effects could occur?
How often will I need appointments, tests, scans, or procedures?
How long will I be in the study?
Will I need to travel?
Which costs are paid by the study?
Which costs may be billed to me or my insurance?
Is financial or travel assistance available?
Who can answer questions from my insurance company?
Can I talk with someone who has participated in a clinical trial?
What happens if I decide to leave the study?

Paige Edmonds smiles while resting her chin on her hand at the Colorectal Cancer Alliance front desk, wearing an Alliance t-shirt and lanyard.

Finding the right clinical trial

Clinical trials are part of cancer care across the full treatment journey. You do not have to search for a clinical trial alone.

The best time to ask about clinical trials is before each new treatment decision.

Ask early. Ask again.

The Colorectal Cancer Alliance’s Personalized Oncology Care team can help you explore possible clinical trials based on information such as your diagnosis and cancer stage, treatment history, biomarker results, overall health, location, and our Care team’s recommendations.

Connect with the Cancer Care team