The “Lost Opportunity” in Phase I Oncology Trials

Cancer drug developers traditionally use the phase I trial solely to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of a drug.  Today, we’ve published a free new downloadable abstract, "The Lost Opportunity in Phase I Oncology Trials," an interview with renowned oncology investigator Daniel D. Von Hoff, M.D.  In the interview, Dr. Von Hoff advocates for a phase I approach that looks beyond toxicity and gleans meaningful efficacy data, creating a more compelling rationale for further investment and improved patient care.

“A Chief Medical Officer looking at the phase I typically sees it as a toxicity trial, not a therapeutic trial, because of course it is not randomized,” Dr. Von Hoff explains. “But we – doctors at the bedside and the patients themselves – do not see it that way. We are looking for improvement and survival. [The phase I] is an opportunity to look for therapeutic effect as well because it might just be there.”

Dr. Von Hoff supports an additional analysis that uses a cancer patient as his or her own control.  Rather than solely relying on the traditional data captured in normal phase I protocols, he recommends measuring the tumor’s “time to progression” on the current drug versus the tumor’s “time to progression” on the patient’s previous treatment.  This data — time to progression on each drug — should be systematically tracked in the protocol so it becomes part of each patient’s data bank.

“I have never seen a CMO plot time on a new drug versus the time on a just-prior therapy to build a story for raising money,” Dr. Von Hoff continues. “This idea of using the patient as his or her own control is a lost concept in drug development. Dr. Bob Temple at the FDA, an icon in clinical trial design, calls it a lost art. He’s referring to the ability to document changes in the natural history of a patient’s tumor, and how this information can give you a sense of whether the drug will work.”

“If you treat 30 patients and 30% stay on a new therapy for a longer time than the just-prior drug they had progressed on, then that would justify a deeper investment,” he explains.  “Patients’ tumors grow at an inexorable, ever-quickening rate. If you find an agent that can taper that growth, then it is probably doing something and should be pursued.”

“There is no question in my mind that, if a CMO started comparing time on new drug versus time on just-prior therapy, the rewards are there – both for the patients and for the progression of the drug. All it takes is a more proactive approach to the phase I. It is so simple yet I have never seen a CMO adopt this.”

In the abstract, Dr. Von Hoff answers many questions about this “lost art” in the phase I trial.  Download the full issue here; you’ll also gain access to the other issues in the series, and we’ll notify you of future publications as well.