Mechanics of Cancer Trials

Types of Clinical Cancer Research Trials

            The research trials available to cancer patients depend on the type and stage of the cancer.  Most cancer patients are interested in treatment trials because they are often searching for potentially new treatments.  Treatment trials usually test experimental agents and collect data on tumor response (change in size of tumor), quality of life, and survival outcomes. 

            If the cancer has already been resected (surgically removed), then adjuvant trials may be offered to investigate which new treatment best reduces the recurrence rate of cancer.  In general, an investigational new drug (IND, also known as study drug or experimental agent) is studied first in the metastatic setting, and if it becomes FDA market approved for metastatic disease, it may then be studied in an adjuvant trial.  For example, herceptin a monoclonal antibody that targets breast cancers expressing Her2 protein has was approved in 2000 for metastatic disease.  It was then studied in two large trials after breast cancer surgery in the adjuvant setting to investigate if it may further reduce recurrence.   In 2005, the herceptin adjuvant trials proved that herceptin may also reduce the risk of breast cancer relapse after surgery.  Herceptin has now become FDA approved for both adjuvant and metastatic breast cancer. 

            A new approach to study the effectiveness of investigational agents is to administer them before surgical resection in neoadjuvant trials (neoadjuvant means before surgery).  Since the tumor is going to be removed regardless, testing a new drug’s effect on the tumor preoperatively enables rapid comparison of drugs’ efficacy.  Essentially, the tumor itself may serve as a testing ground for new drug combinations before it is removed surgically.   Neoadjuvant trials rapidly assess if a new drug combination can completely destroy the tumor, also known as the pathologic complete response rate (when no residual microscopic tumor remains). Neoadjuvant trials are becoming popular in breast cancer before lumpectomy or mastectomy to compare the effectiveness of different chemotherapeutic, hormonal blocking agents, and or biologic agents.  

            The ultimate potential of neoadjuvant trials will be to predict which new drugs are most effective against cancer.   As a powerful example, in the number one abstract (among 3,700) at the 2003 ASCO meeting, oncologists from MD Anderson Cancer Center used gene expression micro-arrays (gene chips) to predict with 78% accuracy and 100% specificity which patients would have a pathologic complete response to neoadjuvant breast chemotherapy.  The significance of this neoadjuvant study was it’s ability to narrow down which genes were involved with tumor regression and provide targets for future drug development.  Undoubtedly, this is the future of cancer research.  Information on this technology may be found at www.affymetrix.com/technology/index.affx. 

            Investigational new drugs are generally first tested in metastatic patients and then brought into the neoadjuvant or adjuvant setting.  However, there are some special exceptions. For example, cancer vaccines may not impact metastatic tumors, but may help prevent recurrence in the adjuvant setting where the tumor burden may only be microscopic. Therefore experimental breast, colon, and melanoma vaccine trails are underway in the high-risk adjuvant setting. 

            Many clinical trials are available for patients who don’t have cancer yet, but are interested in finding ways to reduce their risk of cancer.   Results of prevention trials recently revealed that finesteride reduced the incidence of prostate cancer by 25%.  This past year, the virus that causes cervical cancer, human papilloma virus (HPV) was developed into a vaccine and tested on a large clinical trial for women at high risk of cervical cancer.  The trial results showed the vaccine to be 100% effective at preventing cervical cancer.  Another prevention trial using Tamoxifen reduced the incidence of breast cancer by 50% in high-risk women. 

            Screening trials are another type of clinical trial that attempts to discover cancer earlier when it may be more curable.  For example, screening trials are currently enrolling high-risk smokers by performing annual CT scans to discover lung cancer earlier when it may be surgically respectable.   Since lung cancer is the leading cancer killer, screening trials such as these may have a profound future impact on survivability.  Most smokers are unaware that they may be eligible to participate.