My name is Mallika Dhawan. I’m an oncologist at UCSF. I work in the hereditary cancer center where we try to prevent cancers in patients with high-risk cancer mutations, and then I also work in the Experimental Therapeutics Group, where we are offering new drugs and new therapies, to patients with a variety of different cancers.

What is the purpose of a Phase I Clinical Trial?

In Phase I Clinical Trials most clinical researchers are trying to strike a good balance between answering a scientific question and also answering the need of the patients that we’re seeing in clinic. So Dr. Munster and I sit in her office, every Monday morning actually, and think about the patients that we saw in clinic. Think about what patients we didn’t have a good clinical trial to offer. Think about the gaps in clinical care that we have. That’s really where the trial design starts. It really starts from the point of the patient need.

Can you describe your current trials with BRCA-driven cancers?

So one thing that’s really interesting about tumors that derive from patients with BRCA mutations is that the tumors are really bad at repairing their own DNA, and oftentimes patients ask me, “so, do your drugs help repair the DNA?” The answer is no, not at all. We actually use the tumor’s vulnerability, which is its inability to repair DNA, against it. So we really try to, in our trials, design trials where we’re going to use a tumor, and attack it at its achilles heel. For instance, PARP inhibitors help block DNA repair, and in the trial that I’m currently working on, we’re using a combination of a PARP inhibitor with another chemotherapy as a 1-2 punch against the tumor.

I think when you’re designing trials, there’s a variety of things to consider. The first is the scientific rationale, and for this trial we’re combining a PARP inhibitor known as rucaparib with irinotecan, and so we’re targeting both DNA repair, and DNA replication. There’s also the practical aspect of trial design, and we wanted to choose a drug, i.e. irinotecan, which is approved in a variety of tumor types, so that when patients are on this trial insurance will actually approve their ability to get the drugs.

What group of patients do you see in the Phase I group?

One thing that’s really exciting about Phase 1 trials and working in the Phase I group nowadays, is that patients are coming to us earlier than they used to in the past. In the past oftentimes patients would exhaust all the standard of care chemotherapies that exist, and then come into the phase I group. Oftentimes, at that point they were pretty tired. What I’m liking now is that clinicians in the community will send us patients earlier in their disease course to really stagger new treatments with standard of care treatments, in the hopes that one of these is going to have a long-lasting effect on their cancer.

What drives you to pursue these clinical trials?

What drives me is really working with patients. What I get to do day-in and day-out is talk to patients who are coming in and considering what to do with their time, and my role as I see it, is to properly inform them of their different choices, to help them understand what these drugs are doing, and to help them understand that even if the trial isn’t going well, what they’re doing is valuable, and what they’re doing furthers cancer care and research, and may help other patients.