Clinical trials are the key to improving the prevention, diagnosis, and safe and effective cancer treatment. They are the process through which standards of care are defined. They are the pathways to develop and evaluate more effective and less toxic therapies.
New treatments are tested in a series of trials known as Phase I, Phase II and Phase III trials. New cancer therapeutic agents are evaluated and approved by the US Federal Drug Administration (FDA) only after the Phase III clinical trials have demonstrated evidence of superior outcomes or less toxicity when compared to standard treatments. Similarly, new surgical approaches are uniformly recommended and adopted after Phase III trials demonstrate superior safety, tolerability and/or effectiveness.
Drug studies can begin in patients only after the FDA and a local institutional review boards (IRB) have given approval. The IRB is a panel of scientists and non-scientists in hospitals and research institutions that oversees clinical research. One of the responsibilities of the board is to ensure that clinical trial participants have given consent and are fully informed of their risks, and that researchers take appropriate steps to protect patients from harm.
Prior to a drug even entering Phase I trials, it is well studied to learn about how best to prepare, store and administer the drug. Preclinical testing is usually conducted in animals and human cell cultures.
Importance of Clinical Trials Participation
.Only about 5% of women with a gynecologic cancer participate in the dozens of clinical trials in gynecologic cancers. The predominant hope for improving on the treatment options for women diagnosed with a gynecologic cancer is through the conduct of clinical trials.
The Foundation for Women’s Cancer actively works with the Gynecologic Oncology Group (GOG) to encourage women to participate in clinical trials. Clinical trials are a crucial step in finding new and improved ways to improve treatment for women diagnosed with a gynecologic cancer.
Three examples of the important advances in the care of women as a result of clinical trials include:
- Chemotherapy added to radiation improve cure rate in locally advanced cervical cancer (GOG 120, 109)
- Platinum based chemotherapy plus paclitaxel is superior to platinum based chemotherapy plus cyclophosphamide (GOG 111)
- IP therapy improves survival in subsets of women with newly diagnosed advanced ovarian cancer (GOG 172)
The patients that participated in the phase III clinical trials that led to these discoveries were among the first to benefit from these scientific advancements.
Clinical Trials Phases
Phase I Trials
Phase I trials are the first use in humans and the goal for these trials is to determine the best dosing schedule — the amount of drug, route of administration and dose frequency. Particular attention is directed at learning about the drug or treatments side- effects and any toxic effects. Since these Phase I agents have a limited track record of anti-tumor activity, Phase I trials are usually only open to patients after more established therapies have failed. Initially, low doses that are likely to be non-toxic are used and the dose of the drug is subsequently increased while side effects are carefully measured. Usually between 15 and 50 patients are entered on a Phase I trial. Responses to treatment are hoped for and noted, but the true evaluation of clinical activity against the cancer awaits the Phase II trial.
Phase II Trials
Phase II trials evaluate whether a new drug or treatment is effective against specific types of tumors, for example epithelial ovarian cancer. The dose that was determined to be safe and tolerable during the phase I trial is used. Usually 20 to 200 patients are entered in a Phase II trial in a stepwise fashion. If there are no tumor responses in the first group of patients, the trial is usually closed. In contrast, if there have been a number of patient responses in the first few patients, the trial is often expanded to help better define the percentage of patients who will respond and to help better define the side effects and toxicities.
Phase III Trials
Phase III trials are the largest and most important. Several hundred to a few thousand patients are needed for most Phase III trials. The purpose of these trials is to evaluate whether a new treatment, either on its own or added to another treatment (commonly referred to as the experimental arm) can improve outcomes when compared to an already proven treatment (commonly referred to as the standard treatment or control arm). With experimental cancer treatments, the Phase III trials usually aim to learn whether patients live longer or have longer remissions with the new treatment compared to the standard therapy. While it is the desire and hope that new treatments in Phase III trials will produce a superior outcome, such is not always the case. Sometimes the outcome is no better but the toxicities are worse although this is rare.
On very rare occasions, despite hopeful evidence from Phase I and II trials, the experimental treatment turns out to be inferior to the standard treatment. However, virtually all of the celebrated standard treatments offered today were discovered through clinical trials conducted over past years and decades.
In addition to the three clinical trials phases, there are different types of clinical trials: (1) prevention trials, (2) screening trials, (3) diagnostic trials, (4) treatment trials, (5) quality of life/supportive care trials and (6) genetics trials.