There are numerous regulatory, clinical, legal, and ethical processes and procedures in place to ensure that the potential risk to someone who agrees to participate is minimized. In fact, there's too much for me to easily summarize, so I'll just mention a few of the protections that exist:

• Pre-clinical Testing: Before a drug can be tested in humans, it must undergo rigorous testing in vitro and in animals to identify any risks that might exist. Then regulatory agencies (e.g., FDA and EMA) review the data and either allow or deny test in humans.
• Clinical Trials: There are 3 phases of trials, beginning with small trials with healthy subjects and eventually larger trials involving numerous patients with the disease in question. At every step, safety and efficacy results are analyzed for potential risks and, if necessary, studies are terminated.
• Communication of Risk: Physician investigators and potential subjects are given detailed information about the drug, including risks and benefits, if any. For physicians, this is in the "Investigator's Brochure" and for subjects it's in the "Informed Consent" form. In both cases, the documents must be read, understood, and signed.
• Safety Monitoring: This is an onging process throughout clinical trials during which information about any and all adverse events is continually collected and evaluated for any signs issues.
• Study Design: This is the area that may address your question more specifically because depending on the disease being studied, trials may differ. For cancer trials specifically, placebos are typically not used unless they are given in addition to the best available therapy that exists. Results are then analyzed to determine if there is an additional benefit to the drug beyond what the current treatment alternatives are, and there is no (or very little) additional risk to the patient. Results are also analyzed during the trial (i.e., an interim analysis) to ensure that patients are experiencing some benefit (or the study is terminated due to lack of efficacy) and not experiencing unacceptable adverse events (or the study is terminated for safety).

There are still more safeguards in place, but I hopefully this provides the gist.