I have received many questions regarding the new 3F8 antibody study that is being offered at several institutions throughout the United States. Currently the study "A Study of MAb-3F8 Plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus 13-cis-Retinoic in Primary Refractory Neuroblastoma Patients Acid (RA) Plus GM-CSF" is only being offered at 3 institutions (Phoenix Children's Hospital, University of Oklahoma Cancer Center, and The University of Texas M.D. Anderson Cancer Center in Houston), however, I would expect that number to grow over the coming months to as many as 15 institutions or more.
So, what does this mean to us?
While it is certainly exciting to hear that there is another antibody option available to our children, this one is for a very select group of patients. Secondly, it leaves me wondering, who this might be the "best" option for?
Let me explain.
First, this study is for primary refractory patients. The definition of this group is really the kicker. While it is not explicitly defined for this study in the listing on ClinicalTrials.gov this typically means that this trial would only be available for children who did NOT have a complete remission from front line therapy. This would NOT include patients who achieved a remission and it would NOT include patients who have relapsed. (Two of the groups that would most like to use antibodies and with whom have shown benefit.) Unfortunately, this study is only for patients who have completed front line therapy but have not achieved a remission. This group is further restricted to patients that have evaluable disease or biopsy-proven stable disease in bone marrow by histology or MIBG scan with MIBG-positive disease confined to the bone or bone marrow. However, patients must NOT have measurable disease ≥ 1 cm assessed by CT or MRI. This actually makes good sense though. Solid tumor is unlikely to respond to antibody therapy.
Second, the next big issue to consider is that this is a randomized trial. You either get 3F8 antibody and GM-CSF or Accutane and GM-CSF. Big caveat. If you are a good candidate for antibody therapy, and you know it is effective, why would you enter into a trial with the opportunity to be randomized not to have it? The good news is that this is a crossover trial meaning that patients who do not respond to their assigned treatment after two cycles may "cross-over" to receive the alternate treatment. In other words, there is a good chance you will end up getting the antibody if you have not responded. However, you have to wait at least two rounds and you have to wonder how critical that loss of time will be to the overall goal of producing a remission and saving your child's life. Accutane is good and proven stuff. However, this situation is not known to be where it has been proven to work best. Disease load could be an issue.
I understand the purpose of the randomization to science. It is important. However, to patients, to our children on this trial today, it is not such a good thing and I can't help but wonder (in today's day and age) what I would do. I have to believe that if Sydney were in such a situation I would be more inclined to pursue a trial which would guarantee an antibody or I would be considering something else such as MIBG therapy before I took a shot at randomization.
I say this given two facts. First, there is a good chance that I could be guaranteed to get both Accutane and antibody through another study. I would look at options with ch14.18 and see if I could be eligible and if there is availability. Also, I would look at other options with 3F8. If they do not change the eligibility criteria of existing trials it may be worthwhile to consider high dose 3F8, Sloan's NK cell study or others which could lead to to standard antibody and Accutane therapy without having to gamble one or the other. Second, antibody therapy (most specifically ch14.18 but I also suspect 3F8) has been proven to work in these situations and has been proven to significantly increase survival.
I still can't help thinking.
Why gamble my purpose if I don't have to?