failed before coming to me,” Dr. Saleh says.“ It’ s extremely difficult for these patients to meet the eligibility criteria. We need to think about phase I studies differently than we have thought about them before. It used to be an end-of-the-line option, and it’ s no longer that. In many cases, it may very well be closer to the front of the line.”

Dr. Saleh’ s message for patients and referring physicians is that phase I studies should be considered sooner rather than later.“ We shouldn’ t wait until the end of the line to refer a patient to a phase I study,” he says.“ We are here to say if you don’ t have an FDA-approved option, consider a phase I trial.”

“ What we can best do for the patient should be our goal. We have a highly trained and compassionate team, all dedicated to this concept of giving the patient the drug called hope.”

Mansoor Saleh, M. D. UAB Comprehensive Cancer Center senior scientist and director of the Phase I Program

The Role of the Cancer Center

The Cancer Center has long been a tremendous supporter of the Phase I Unit and was instrumental in its creation. The program currently has 16 open trials, nearly all of which are oncology-related and more than double from when the program started. Some are studying hematologic malignancies, while others involve solid tumors and the rest are considered“ catch-all.”“ We are ambitious in our goal, but pragmatic and focused in our approach. With our disease-specific as well as catch-all, first-in-human trials, we have something for every patient,” Dr. Saleh says.

“ While the objective of a phase I study is safety, tolerability and pharmacokinetic profile of novel drugs never administered to patients before, we are seeing more and more combination phase I studies, where an FDA-approved agent is delivered with the study agent. In many ways, such phase I trials also offer the real potential for some biologic and clinical activity,” Dr. Saleh says.“ But, it is important to know that we are still in the experimental phase and do not have data to make any claim of benefit.”

The Phase I Unit has a number of trials that are target- or pathway-specific. For example, if researchers are studying a drug’ s effect on a certain gene mutation or cell-survival pathway, only patients with that“ actionable signal” would be eligible for the trial. That target, however, could appear in a number of cancers. Thus, a number of the phase I studies are geared toward a broad range of cancers.

The Phase I Program also has a number of trials involving the human body’ s natural disease fighter – the T-cell.“ There is an entire army of drugs that stimulate the immune system and its T cells,” Dr. Saleh says.“ However, we have not been able to activate the T-cell and help it fight cancer cells effectively, because cancer cells produce proteins and chemicals that inhibit the actions of the T-cell. We now have drugs that activate those T-cells and overcome the inhibitory impact of the tumor cell.” An example of these types of agents are the“ check-point” inhibitors, including, for example, the drug given to former President Jimmy Carter to treat his melanoma.“ In our Phase I Program, we have a number of FDA-approved check-point inhibitors being administered with novel new drugs aimed at activating the cancer-fighting potential of the body’ s own immune mechanism,” Dr. Saleh says.

The challenge with any clinical trial, including phase I studies, is that patients must meet an often extensive list of eligibility criteria. Overall health – termed Performance Status – is an important factor, as are baseline laboratory studies, the stage of the cancer and having measurable target lesions, just to name a few. This goes a long way in explaining why not all patients can qualify for a clinical trial, because the only way to study new agents is to have a strictly defined patient population and to strictly adhere to the protocol.

“ When I see patients in my clinic, many have had five or more prior treatment regimens that have