What Are the Phases of a Cancer Clinical Trial?
Clinical trials for cancer test various treatment types, such as new drugs, radiation therapy, surgery, immunotherapy and treatment combinations or methods. A cancer clinical trial is the first step in testing treatments in human beings, so doctors can identify better methods of diagnosing, treating, managing and preventing cancer.
Each new treatment goes through clinical trial phases, and each phase is designed to answer specific questions about the newly tested treatment. Researchers perform clinical trials when they believe a treatment or test will improve patient care.
Cancer clinical trials are designed to test new methods to:
- Find and diagnose cancer.
- Manage symptoms of cancer.
- Manage side effects from cancer treatment.
- Treat cancer.
- Prevent cancer.
The stages involved in a cancer clinical trial may involve:
- Preclinical Research
- Phase 0
- Phase 1
- Phase 2
- Phase 3
- Phase 4
The three main trials are 1, 2 and 3. In oncology clinical trials, phase 0 is typically omitted, and in others, phase 4 is carried out after the drug has been approved for commercial use.
The Importance of Clinical Trials
If there were no clinical trials, there likely would not be any new cancer breakthroughs or treatments. In most cases, U.S. doctors are not allowed to use experimental treatments or drugs on patients unless they are carefully studied, and the Federal Food and Drug Administration (FDA) has approved it to use on patients.
FDA professionals carefully analyze a clinical trial's results before determining whether new treatments are more effective and safer than established standard treatments. For new cancer treatments, drugs and therapies to be marketed in the U.S., they need the stamp of approval by the FDA.
Potential Benefits of Clinical Trials for Cancer
There are some potential benefits to the stages of clinical trials, which may include:
- A clinical trial offers the opportunity for high-quality cancer care.
- A patient may be the first to get positive results from a new treatment.
- A patient can take an active role in something that could affect their life.
- A patient can help improve treatment for cancer.
- The company sponsoring the clinical trial covers all of the costs associated with the patient’s involvement in the trial.
Potential Drawbacks of Clinical Trials for Cancer
Of course, there are potential problems with clinical trials as well, which may include:
- A clinical trial treatment may not always be as good as or better than the standard cancer treatment.
- There could be side effects, and they could even be worse than those of standard treatment.
- Treatment may not work for every patient (this is the same with standard treatment).
- Participation in a clinical trial may be inconvenient or take extra time.
- Participation in a clinical trial may require the patient to take additional medications or tests.
The Cancer Clinical Trial Process
Clinical trials for cancer are conducted in a series of sequential steps, called phases. Each phase is intended to answer a specific question.
During a clinical trial, patients receive treatment, and the physicians conduct research on how the patient is affected by the treatment. Doctors closely monitor the patient during the trial. After completion of the treatment, the patients usually still are monitored so the doctors can collect information about the progression of the disease, overall survival and side effects of long-term use.
When a patient signs a consent form that does not mean they are obligated to stay in the clinical trial. A participant can leave the trial at any time. If participants decide to leave the trial, they may speak with their doctors about other treatment options. If a participant chooses not to participate in a trial, their health care won't be affected in any way.
The majority of the time, when a patient participates in a clinical trial, they are only part of one particular phase of the trial. They do not typically move through all the phases of clinical trials, only the treatments do.
Preclinical Research for Cancer Trials
Before beginning any clinical trial in humans, physicians must prove their proposed treatment description is correct in what is known as the preclinical research stage. During preclinical research, researchers evaluate the treatments and tests before the clinical trial begins.
People are not involved in preclinical research. Instead, this phase is set up to evaluate the features of a treatment or test. For instance, the objective may be to learn if a certain device can harm living tissue. Another goal may be to determine a drug's particular chemical makeup.
This stage could take years before a new treatment evolves. If the research from the preclinical stage finds that the proposed treatment is an effective cancer treatment, the sponsor of the clinical trial files an Investigational New Drug (IND) application.
Once preclinical research has been completed, the treatments and tests are put through a sequence of clinical trials to see if the treatments or tests work in and are safe for people. Contact us to learn about how TD2 can support all of your preclinical research needs.
Phase 0 Clinical Trials: Should a New Treatment be Tested in a Phase 1 Clinical Trial?
This phase is an exploratory phase. The main difference between later clinical trial cancer phases and phase 0 is that there is only a minuscule chance a patient will benefit from participating in this exploratory phase.
Phase 0 studies help researchers:
- Determine whether the drug does what it is expected to do.
- Learn if there are problems with the way the drug acts or is absorbed in the body.
If a drug doesn’t act as expected during phase 0, it helps to avoid the expense and delay of finding this out years later in phase 2 or even phase 3 clinical trials. In essence, the hope of this stage is to help streamline and speed up the drug development process.
The Length and Number of Participants in Phase 0 Clinical Trials
Phase 0 studies are not required to get a new drug approved. They are also not used widely. As such, participation in a phase 0 study is small, quite often with less than 15 people.
Also, patients receive only small doses, known as microdoses, in this phase. Because the dosage in this stage is small, less than one percent, the risk of side effects is lower than in other later stages. The length of this phase is short and may last fewer than seven days. Because of this, a Phase 0 is not typically utilized in cancer drug development.
Phase 1 Cancer Clinical Trials: Is the Treatment Safe?
The primary question to be answered in the phase 1 clinical trial is whether the treatment is safe. The participant's safety is at the forefront of phase 1 of a clinical trial. This is especially true with trials that test new oncologic treatments where participants could be put at risk of possible toxic treatments, with the goal of slowing down or curing their disease.
The phase 1 cancer clinical trial results help progress a new treatment further into drug development or may halt the process altogether. During phase 1 clinical trials, the benefits and risks to the participants are explored, as is determining a safe dosage and identifying side effects.
Physicians increase the experimental drug slowly during a phase 1 trial. The objective is to determine what dose works most effectively without triggering serious side effects. The research community refers to this as “dose escalation.”
The first participants in the trial will receive a low dosage of the experimental drug. These participants will then receive higher doses of the drug if they do not present any side effects or very few. This increasing dosage process continues until physicians determine the highest dose they can administer with the least side effects.
In some cases, the physicians need to figure out the best way of administering a new drug or treatment. This could be for example through a vein or mouth. The physicians will also gather up data on:
- How the drug is absorbed by the body.
- How the drug is used by the body.
- How the drug spreads through the body.
Although these trials are not intended for doctors to see how well a particular treatment by itself or combined with other treatments works, sometimes a treatment given to a patient during this phase does slow or halt cancer in the patient. Phase 1 trials do not involve the use of placebos, inactive treatments.
In general, phase 1 trials have the most probability of risk, but they are helpful to some patients. It’s essential for patients whose cancer is life-threatening to weigh the possible risks along with the benefits.
The Length of Trial and Number of Participants in Phase 1 Clinical Trials
A phase 1 trial typically lasts anywhere from a few months to a year. There are usually about 10 to 30 participants involved in a Phase 1 clinical trial, according to Cancer.net. In a phase 1 trial, the physicians offer treatment to patients who aren't responding to standard cancer treatments..
Phase 1 cancer clinical trials represent a beneficial option for those patients who move forward through frontline therapy for their cancer. Recent trials in the first phase that test specific treatments have increased responses where other lines of treatments failed. While enrolled in a phase 1 clinical trial, participants still face a number of benefits and risks.
Choosing the Participants for Phase 1
There are regulations and rules in place for protecting the interests and safety of participants undergoing clinical trials. Researchers and doctors face challenges selecting cancer patients who will be available long enough to gather information for the trials.
Newly validated prognostic models help researchers and doctors choose the patients who will potentially benefit the most from participating in a phase 1 trial. There could also be long-term positive and negative effects on patients who decide to become a participant in a phase 1 cancer clinical trial.
Phase 2 Cancer Clinical Trials: How Does the Treatment Work, and How Does the Cancer Respond?
A phase 2 cancer clinical trial provides information to doctors about the efficacy of the cancer drug and to further the evaluation of its safety. Phase 2 trials also help doctors determine if the new treatment will work for a specific cancer type as well. There are no placebos given in a phase 2 clinical trial.
Physicians may analyze results of a blood test or measure the size of a tumor to determine if the treatment is working or not. The kind of response and benefit the physicians look for depends on the objective of the treatment. It could be the cancer becomes smaller or goes away altogether. Alternatively, it could be the cancer does not grow for a lengthy extent of time or the cancer does not come back for a longer length of time.
Patients may see an improvement in the quality of life in some phase 2 studies. Other studies are conducted to determine if patients who receive the new treatment live longer than what is expected if they did not get the treatment.
Before research can move forward to phase 3, physicians have to demonstrate the new treatment is as safe as standard treatment and is likely to work.
The Length and Number of Participants in Phase 2 Clinical Trials
Phase 2 trials take around two years. They usually involve between 30 and 120 participants, per Cancer.net. In some cases, researchers assign different people to several potential treatments during a phase 2 trial. Phase 2 may compare standard treatment alone with the standard treatment combined with the new treatment.
It could also involve different dosing of the treatment for certain people. The process is known as a randomized phase 2 trial and could include a few hundred patients.
Phase 3 Cancer Clinical Trials: Is It Better Than the Standard Treatment Already out There?
In a phase 3 cancer clinical trial, researchers and doctors compare the results of patients taking the new treatment with the results of those taking a standard treatment. A couple of questions explored in this phase:
- Which group of patients has the best survival rate?
- Which group of patients has fewer side effects?
Participants are randomly assigned to receive the new treatment, referred to as the “treatment group,” or the standard treatment, known as the “control group.” The process of randomly assigning patients, similar to the process of flipping a coin, is to avoid bias where the results of the trial are affected by factors not relevant to the study treatments or by human choices.
In the phase 3 trials, placebos may be involved and compared with a new treatment. However, the participants know of this possibility before they decide if they want to participate in the trial.
An additional way to ensure the results of the trial are real is to compare similar groups of participants who are taking a different type of treatment for the same form of cancer. This comparison shows the treatment was responsible for their results instead of by chance or other reasons.
The Length and Number of Participants in Phase 3 Clinical Trials
There could be hundreds to thousands of participants in a phase 3 cancer clinical trial from various centers around the U.S., according to Cancer.net. A phase 3 trial may include participants of different genders, ages and ethnicities to help physicians apply the results to a larger number of patients. It can take many years to complete a phase 3 clinical trial.
Food and Drug Administration Approval Submission in Phase 3
The Food and Drug Administration, or FDA, becomes involved in phase 3. Once treatment is shown to work effectively against a certain type of cancer, it needs to go in for FDA approval. During this process, the FDA reviews the clinical trial results and other data and decides whether to approve the new treatment for patients to receive for the tested cancer type.
If the clinical trial data meets FDA standards, the FDA approves the treatment for a specific use, and then it becomes part of the standard of care for cancer patients. If the FDA decides it needs more evidence to prove the benefits of the new cancer treatment outweigh the risks, more studies may be conducted.
Phase 4 Cancer Clinical Trials: What Else Do I Need to Know About the Long-Term Benefits and Side Effects?
The phase 4 cancer clinical trial tests the FDA-approved treatments. Phase 4 is conducted after the FDA approves a cancer drug for licensing and marketing. Physicians study how well the treatment works and if it is helpful when combined with other drugs or treatments. Most phase 4 research is conducted at physicians’ offices, where patients go to for their medical exams and prescriptions.
The Length and Number of Participants in Phase 4 Clinical Trials
Thousands of participants are typically part of the phase 4 clinical trial. These participants have been under medical supervision and have taken the drug for an extensive period. During phase 4, the drug is tested on varying demographic groups. For example, a drug may be tested on pregnant women to see if it causes a reaction in this group.
With a large number of participants in phase 4, doctors and researchers can better research the safety of the treatment as well as the short-lived and long-lasting side effects. Phase 4 is intense and long-term. Patients do not necessarily have to enroll in a study to get the phase 4 drugs.
The care patients receive in a phase 4 trial is similar to the treatment they would get outside the trial. However, in a phase 4 trial, the patients are actually helping doctors and researchers gather more treatment information to help them to treat future patients.
Are Clinical Trials for Cancer Dangerous?
There are side effects with experimental treatments, and some could be dangerous or unpleasant. However, standard treatments may also have dangerous side effects. Researchers and doctors closely monitor clinical trial participants and look for early signs of side effects and complications. If problems develop, the experimental treatment stops immediately.
In addition, an Institutional Review Board (IRB) must approve all clinical trials first. IRBs are made up of doctors, community members and scientists who review the studies in advance to ensure the benefits of the trial to the study participants outweigh any potential risks. Therefore, although every cancer clinical trial can pose risks to the participants, specific steps protect the participants.
What Are the Cancer Trial Protocols?
Cancer clinical trials follow protocol. This is the action plan. This plan outlines actions performed in the trial and why. It details the number of participants in the trial, which patients can participate, the testing they will get and how often and the plan of treatment.
Doctors use the same protocol when treating patients and all guidelines are followed. The FDA-specified guidelines must be adhered to by any doctor or institution involved in the clinical trial. All results of a clinical trial are audited before the FDA can approve a treatment to ensure the trial is safely conducted and follows all guidelines. All protocols need to be approved by the sponsoring organization of the clinical trial to ensure the patient's safety.
Contact TD2 for Help in the Development of Your IND Through the Phases of a Cancer Clinical Trial
At TD2, we assist companies like yours in moving the development of your Investigational New Drug (IND) Application for your new oncology medicine through phase 1, 2 and 3 clinical trials as efficiently as possible. We help you identify key patient populations who are most likely to respond to your drug compound and help discover avenues to shorten your development timelines — all the while ensuring the new drug is safe and effective.
We also provide compliance and regulatory expertise to ensure your compounds meet FDA standards and swiftly move into clinical development. Complete our form to contact us for more information on cancer trial phases and how we can help with your IND and clinical trial process.
Each phase of a clinical trial is intended to answer a specific question.
According to the American Cancer Society, a new cancer drug has been studied for 6 years on average before it makes it to clinical trials. The average time it takes a new drug to reach approval after entering a clinical trial is 8 years.
Have researchers completed an initial evaluation of the proposed treatments and tests and verified them?
No – Keep researching or propose new treatment
Phase 0 [Optional]
Does the drug do what’s expected?
No – Research a new treatment.
Does it meet the requirements?
- Is the treatment safe?
- What dosage works best?
- Did doctors choose the optimal method to administer the drug?
No – Research a new treatment.
Does it meet the requirements?
- Is the treatment effective against a specific type of cancer?
- Do the benefits out-weigh the risks?
No – Research a new treatment. Treatment is stopped if side effects are too severe.
Does it meet the requirements?
- Is it better than the standard treatment?
- Did the FDA approve the treatment?
Yes – The treatment is approved! Study Ends. Written Report created and sent to scientific publication(s). Clinical Trial Registration File submitted.
No – Re-do Phase 3 trial. Treatment is stopped if side effects are too severe.
Does it meet the requirements?
- Is the drug safe and effective long-term?
- Is the drug effective when combined with other treatments?
- Can the drug treat other symptoms?
Yes. FDA can choose to remove certain warnings from packaging if supported with enough research. The FDA can also allow companies to promote other loosely associated conditions. No – All original warning labels present must remain on the package. Companies can’t market the drug outside the original FDA guidelines.