by Dr. C.H. Weaver M.D. 8/2022
When you or a loved one are diagnosed with cancer, it is important to know all of the treatment options available in order to make the best decision about your cancer treatment. This may include clinical trials, which are research studies designed to evaluate new cancer treatment options. Clinical trials test the safety and effectiveness of treatments, many of which are only available through participating in a clinical trial. Trials evaluate new anti-cancer drugs, unique approaches to surgery and radiation therapy, and new combinations of treatments. In the United States, the Food and Drug Administration (FDA) oversees the conduct of clinical trials.
What does the FDA do?
The FDA is a government agency that is responsible for making certain that the food we eat and the drugs we take are safe. The FDA does not make drugs or directly test drugs to determine if they are safe and effective. The FDA’s role is to oversee the research conducted by pharmaceutical companies, university research centers, and physicians to make certain that federal regulations governing research are being followed.
The FDA requires that the drug company’s plan must be reviewed by community research review board (IRB), and that patients participating in the clinical trial are informed about the trial and consent to participate. Once the drug company has completed its clinical trials, the data are tabulated and submitted to the FDA in an application known as a New Drug Application (NDA). The FDA evaluates the outcomes reported in the NDA and determines whether the new drug will be approved and made available to patients in the United States. In order to be approved, the drug must be safe and effective.
Can I get a drug before it is approved by the FDA?
Until a drug receives FDA approval, it cannot be sold and the drug company may only provide it to patients through clinical trials. Furthermore, each clinical trial has specific criteria that patients must meet to be included. Occasionally, a cancer patient who is not eligible for a clinical trial may receive a promising unapproved drug, if the patient’s doctor, the drug company, and FDA each agree. The FDA’s primary interest is helping to ensure that the drug company’s research will not subject cancer patients in the clinical trial to undue risks. The FDA drug review process guarantees that the risks and benefits of a cancer drug have been carefully considered before it is approved and helps to ensure the public that marketed drugs are safe and effective.
How can I learn more about a drug that has been approved?
The FDA requires that all drugs have an information document for healthcare providers and consumers called a “package insert.” This document is a summary of the essential scientific information needed for the safe and effective use of the drug. You can ask your doctor for this information. Also, most package inserts are available on the internet. A package insert typically includes the following information:
- Chemical structure
- Information about how the body absorbs, distributes, metabolizes, and excretes the drug
- Results from some clinical trials
- What specific circumstances the drug is used for
- Dosing and administration schedules
- Side effects
It is important to understand that once it has been determined that a drug is safe and it is approved by the FDA, physicians often use the drug for the treatment of medical conditions other than the specific condition that the FDA has approved it for.
Are all clinical trials the same?
Development of new anticancer drugs and treatment strategies occurs in four phases. Each phase is designed to determine specific information about the potential new treatment such as its risks, safety, and effectiveness compared to standard therapy. The hope is that the new therapy will be an improvement over the previous standard therapy.
Phase I Trials: This phase is probably the most important step in the development of a new drug or therapy. Phase I therapy may produce anti-cancer effects and a small number of patients may benefit, however, the primary goals of this phase are to determine safety issues, which include:
Understanding DNA Damage Response or DDR and Cancer Treatment
What is DNA Damage Response or DDR?
- The maximum tolerated dose of the treatment,
- The manner in which the drug works in the body,
- The toxic side effects related to different doses, and
- Whether toxic side effects are reversible.
Phase I trials usually involve a small number of patients for whom other standard therapies have failed or no known alternative therapy is available. Upon completion of phase I trials, the information that has been gathered is used to begin phase II trials.
Phase II Trials: Phase II trials are designed to determine the effectiveness of the treatment in a specific patient population at the dose and schedules determined in phase I. These trials usually require a slightly higher number of patients than phase I trials. In general, all of the patients participating in a phase II trial will receive the treatment that is being investigated. Drugs or therapies that are shown to be active in phase II trials may become standard treatment or be further evaluated for effectiveness in phase III trials.
Phase III Trials: Phase III trials compare a new drug or therapy with a standard therapy in a randomized and controlled manner in order to determine proof of effectiveness. Phase III trials require a large number of patients to measure the statistical validity of the results because patient age, sex, race, and other unknown factors could affect the results. To obtain an adequate number of patients, several physicians (investigators) from different institutions typically participate in phase III clinical trials.
Phase IV Trials: Once the drug or treatment is approved and becomes part of standard therapy, the manufacturer of the drug may elect to initiate phase IV trials. This phase includes continued evaluation of the treatment effectiveness and monitoring of side effects as well as implementing studies to evaluate usefulness in different types of cancers.
Incurable cancers in oncology trials
The US Food and Drug Administration (FDA) issued final guidance on the inclusion of patients with incurable cancers in clinical trials for investigational therapies in August 2022.
The agency recommended sponsors include patients with incurable cancer—defined as unresectable, locally advanced, or metastatic disease in solid tumors and/or hematologic malignancies with unfavorable long-term overall survival—in oncology clinical trials even if they met criteria that would otherwise exclude them, such as in situations where a patient had previously received an available therapy in a non-curative setting. The recommendation by FDA emphasizes that sponsors still need to follow regulations around informed consent before enrolling patients with incurable cancer in clinical trials.1
There is currently no single source of all clinical trials. The following are clinical trial resource is a good place to start.
- NCI’s Web site at www.cancer.gov