Mets Day 908: From clinical trial inquiry to hospitalization

This morning I received a call from Brenda Robinson, the clinical trial coordinator for Dr. Lauren Wood at NIH. Ms. Robinson told me that she was interested in getting me to participate in a clinical trial relating to a customized immunotherapy the used the fact that my cancer had HER2/neu overexpression. She said that she had an immediate slot available for me, and asked if I could come in that afternoon for a CT screening. Although I did not have enough information to determine whether I wanted to participate in that particular trial, I agreed to go in for the scan and get more information.

Two hours later, I was at NIH. I went to phlebotomy for the blood draw and urine test, then went to radiology for the CT scan. The receptionist said that she did not yet have my orders from the doctor, so I went upstairs to the clinic to find Ms. Robinson. She quickly appeared and was surprised that the orders were not yet entered. She went to the computer and got everything set up, and returned with an 11 page disclosure about the clinical trial. It was NIH NCI Study No. 13-C-0016: Phase 1 study of adenoviral transduced autologous dendritic cell vaccine expressing human HER2/neu ECTM in adults with tumors with 1-3+ HER2/neu expression. I started reading through the disclosures when Ms. Robinson said that Dr. Wood was available to meet with me and explain a bit more about the trial.

Dr. Wood was joined by a team of 5: a fellow, two medical students, and two nurses. She enthusiastically explained the intent of the trial.  I learned that this was a first-in-human trial for a new type of customized immunotherapy. She explained how my cancer had tested positive for HER2 overexpression (the test results were plus 3). The HER2 protein sends signals to tumor cells to make them grow and preventing the tumor from dying. HER2 overexpression has been studied extensively in connection with breast cancer, where it is present in 25-30% of cases. The HER2 genome is responsive to several medicines, including trastuzumab (Herceptin), pertuzumab (Perjerta), and ado-trastuzumab emansine (Kadcyla), which are monoclonal antibodies that recognize and inhibit distinct portions of the HER2 protein. The drugs have to be administered repeatedly to have an effect, and they don't necessarily work on all HER2 cancers.

The clinical trial involves the creation of a AdHER2 DC vaccine to induce the patient's own immune system to make multiple, different types of antibodies to HER2, called polyclonal antibodies. Mammalian studies have shown that a AdHER2 DC vaccine has caused significant regression and shrinkage of large established tumors.  A YouTube video of this trial is available here. The objective of the trial is to see if the vaccine that works in mammalian studies can be translated to humans. Because monoclonal antibodies such as trastuzumab can adversely affect cardiac function in some patients, the FDA is requiring this trial to closely monitor cardiac function.

I was told that the trial would consist of the removal of certain types of my blood cells through a process called apheresis, where my blood is drawn, run through a cell separator machine to take out my circulating cells (including lymphocytes and monocytes), and the plasma and red cells returned to my body.  The circulating cells are then used to custom make a vaccine. Enough circulating cells are removed during apheresis to make 5 or 6 batches of vaccine, using my own dendritic immune cells. Those dendritic cells are derived from the monocytes in my circulating cells.  The NIH doctors would mix in a combination of trastuzumab, pertuzumab, and ado-trastuzumab emansine into that vaccine, then would inject it transdermally (under my skin).  The protocol calls for 5 rounds of injections: weeks 0, 4, 8, 16, and 24, as well as two years of monitoring.

After trying to digest all of this information, I went back downstairs for the CT scan. The tech was unable to get a return blood draw from my port, suggesting that there was a clot or other type of blockage around the tip of my port. She was able to inject heparin into my port, however, so we used it for the injection of the contrast during the CT scan. While waiting for my CT scan, I sent an email to Dr. Apolo, asking for her input on whether she thought that I should enter this particular clinical trial.  After summarizing the trial, I wrote:

I am most interested in your thoughts on whether I should participate in this study, or instead enroll in either your PD-L1 study, or the MPDL3280A study, or some of the other trials that we had discussed. My initial impression is that, because the HER2 study is a first-in-human phase 1 trial and the therapeutic effect is unknown, it might be better for me to enroll in a PD-L1 trial instead. Or should I take a stab at this, then do the PD-L1 trial later? Or vice-versa? 

I left for home after the scan. I was told that I should plan on coming back to NIH tomorrow for a bone scan, echocardiogram, and further discussion of the trial protocol. I stopped at Chipotle on the way home, as I had not eaten since the night before. While walking into Chipotle, Dr. Apolo called me. She said that she had told Dr. Wood about me back in August, but expected that Dr. Wood would have spoken with her before contacting me. She recalled that we had decided to wait until my next scan on November 18 before deciding what course of treatment, if any, and seemed surprised that her colleagues had initiated contact with me about a trial. While praising Dr. Wood's innovative research with the AdHER2 DC vaccine, Dr. Apolo noted that it was a first-ever Phase 1 trial, and there was no evidence that it would work in humans.  By contrast, the PD-L1 trials had shown significant response in more than 50% of study participants. She said that, while it was nice to have choices on trials, she would recommend that, if I was to choose to enter a trial, she would recommend that I participate in a PD-L1 trial. She proposed that I defer for at least a week my decision on whether to enter Dr. Wood's HER2 trial, and in the meantime Dr. Apolo would review the results of today's CT scan, and meet with me on Tuesday, October 14. That sounded sensible to me.

Five minutes after I got home, I was called by Dr. Wood. She said that she had just reviewed the results of my CT scan. She said that it showed a large clot in a vein in my liver, and multiple clots in the lower lobe of my right lung -- a serious case of pulmonary embolism, or PE. She asked me to immediately return to the NIH hospital for administration of blood thinners. She said that I likely would be in the hospital for a day or two. I briefed Jennifer, jumped back in the Audi and went back to NIH. After I was admitted, I met with Dr. Wood, who had waited for my return. She explained that mets cancer patients were at increased risk for PE. She said that the best treatment would be for me to have two subcutaneously injections daily of enoxaparin (Lovenox).  She said that this was more effective in patients with a cancer burden than IV-administered unfractionated low molecular weight heparin.

So now I'm reclining in my hospital bed watching the Deadskins get thumped by the Seahawks. At around halftime, the nurse came if to inject the Lovenox into my abdomen. She admired my love handles, and said that they were perfect for the injections. I smiled with the knowledge that the decades of preparation for this day has finally paid off. I'll get another injection tomorrow morning, and then probably will get trained on injecting myself. I'll have to do the injections twice a day for the next month or so, then may be able to shift to oral therapy. Whether by serendipity or a bit of divine intervention, I'm grateful that the PE was detected without my suffering any harm. It was (ahem) a stroke of good luck.