Levin Discusses Future of STELLAR Trial

Victor Levin, MD

Eflornithine in combination with lomustine (Gleostine) is being studied in patients with recurrent anaplastic astrocytoma for the STELLAR trial (NCT02796261) and, if treatment is successful, it will be the first targeted therapy for this patient population.

“We have not had approval of any drug for primary gliomas since the alkylating agents,” Victor Levin, MD, said. “There are no other drugs available today to treat gliomas other than alkylating agents, so this would be a real game changer because it would add a new drug, a new mode of action, and an agent with a limited toxicity profile. It would provide the neuro-oncology community an opportunity to…create new combinations based on the mode of action of [eflornithine].”

Levin is an attending physician at Kaiser Permanente Redwood City Medical Center; clinical professor in the Department of Neurosurgery at the University of California, San Francisco Medical School; and an emeritus professor in the Department of Neuro-Oncology at The University of Texas MD Anderson Cancer Center. At the 24th Annual Meeting and Education Day of the Society of NeuroOncology, he spoke withTargeted Oncologyabout the STELLAR trial.

TARGETED ONCOLOGY: Can you describe the design of the STELLAR trial?

Levin:The STELLAR trial is a study that's designed for approval by the FDA and it's a new drug application study. It is a final, phase III randomized trial to treat patients with anaplastic astrocytoma at recurrence with either lomustine, which is the standard of care, or the combination of lomustine plus eflornithine—eflornithine being the experimental therapy.

TARGETED ONCOLOGY:Have there been any results so far?

Levin: We don't see results because the study is blinded to the outcome so that an independent contract research organization runs the study for the company, Orbus Therapeutics. The only thing we know with reasonable certainty is the toxicity patterns of the 2 therapies. We know that it's acceptable, and the study moves ahead. We won't know the outcome until we meet certain milestones, like if a certain number of patients have progressed. When we get to that point, then statisticians for the data monitoring committee can make a determination. The committee at that time can say [we] should stop the study or continue the study. We don't know the outcome at this point.

TARGETED ONCOLOGY:What's the next step for this study?

Levin: We basically wait. We think it will take somewhere between [12 to 18 months] to complete the study and have our first independent review of the data.

TARGETED ONCOLOGY:Will there be a follow-up study for STELLAR?

Levin: We won't need a follow-up study [if eflornithine plus lomustine receives] approval. If this is successful, we have it in writing from the FDA that the drug will be approved. There are other studies we would do with this drug though if we had a choice. We would like to use the drug [in the] upfront [setting]. Say with temozolomide plus [eflornithine]. We think that it would become the new treatment of choice, and it would add a certain amount of efficacy and safety to the use of temozolomide. That study will take a decade [to complete] because of the increase in survival that the therapy can produce and the known outcomes that we have today, so it's hard to support a study like that with venture money.

TARGETED ONCOLOGY:How is STELLAR different than other trials in the setting?

Levin: There are no [other trials like this]. This is the largest trial ever for recurrent anaplastic astrocytoma; nobody has ever mounted a study this big. We do not know of any other [randomized] study focused [on] recurrent anaplastic astrocytomas at this time so, as far as we know, there's nothing else available right now [or that] would be available in the next couple [of] years. New drugs come along but [investigators are] going to run into some of the same problems we have, which is getting support to conduct these long-term studies in a tumor like anaplastic astrocytoma. It's a rare disease.

TARGETED ONCOLOGY:What do you hope to happen if the trial is successful?

Levin: It would go to market and it would be accessible to the community [of] physicians. They would be able to use it for their patients, and I believe patients will live longer and the toxicity will be tolerable.

TARGETED ONCOLOGY:Are there other studies in similar settings that you feel are important?

Levin: There are studies going on with glioblastoma. I think that it's hard to predict what's going to work because historically nothing has. Will some of the new ideas, new signaling molecules, and new immunotherapy approaches work? I don't have any basis to say one way or the other at this time. Some of the studies are [early] and for some of them, the investigators are very confident but we don't see the data yet so I'd say that I have an open mind. I don't see anything directly in front of me that says this is likely to be a sure thing for new therapy as a result of a trial.

TARGETED ONCOLOGY:Is there anything else you are planning to work on?

Levin: I think my focus [has been on] just this trial. I will be happy if, when this trial is finished, we can move forward with this drug, try other combinations, and get it into the market to help people.

TARGETED ONCOLOGY:What other combinations would be possible if the trial is successful?

Levin