Update on the PRI724 Trial and Other Trials

Dr. Lenz

Because of the overwhelming response to my earlier post on PRI724, I wanted to clarify a little bit more about this trial and other trials available for patients with advanced colorectal cancer who have received all standard of care regimens including FOLFOX, FOLFIRI, Avastin and Erbitux (if they were wild-type KRAS).

Of course we will have PRI724. The reason we are so excited because it is the first in class to inhibit a pathway so essential for colon cancer stem cells.

The IND is filed at the FDA, which means we need to wait 30 days for the FDA to respond. If they have concerns, we need to answer them. When they agree, we will go ahead to get institutional review board (IRB) approval. We already have scientific approval from the Cancer Center Scientific Review. Once we have IRB approval we are ready to go.

In the first phase any solid tumor is eligible. However, phase I trials are heavily regulated, so patients need to meet eligibility criteria, which means almost normal function of renal, liver, blood etc. They have to be in reasonable shape (able to do their daily activities). We anticipate that this trial may open at the beginning of November.

This is a phase I trial, which means we are dose escalating to find out if there are any side effects. We don’t expect any. In fact we are worried that there will be none, which will make it difficult for us to decide what dose to use to move forward.

We have decided to measure concentrations of the drug in the blood stream and changes in the tumor cells to determine when the drug is effective, and then expand the dose to colon and pancreas cancer.

In addition, over the last year a lot of novel therapies have been developed and we have two trials open for patients with mutant KRAS,  one for patients who received FOLFOX/Avastin who never had irinotecan, have mutant KRAS, and whose tumors continue to grow.  For patients who had all therapies we have another trial.

We also have trials with novel compounds which focus on the VEGFR, but not VEGF like Avastin does. VEGFR is the receptor to which VEGF binds and may work when anti-VEGF does not work. This is a phase III randomized trial using an antibody against VEGFR. The control arm is no treatment.

We have openied a novel trial using lapatinib and LBH and LBH with 5-FU. These novel drugs attack specific alteration in the colon cancer cells. Both combinations were tested in vitro and in animals showing promising data, so we wrote them up for clinical trial.

We have a EPO906 trial which has shown to shrink tumors in patients who had all standard treatments and where those treatments stopped working.

We have phase I trials with inhibitors of Hedgehog, NOTCH, MEK, and others, which are novel smart drugs effecting specific genetic switches turned on in colon cancer. Also there are other trials which also make a lot of sense depending on the molecular make up of your tumor.

I hope this clarifies some of the questions that readers had.

From the Editor

You can find a complete list of gastrointestinal cancer clinical trials currently available at the University of Southern California Norris Cancer Center online.  Look for Dr. Lenz’s name as Principal Investigator and for colorectal somewhere in the name of the trial.

Some trials may also be available closer to where you live.  Others are limited to USC Norris.

The Clinical Investigation Support Office at (323) 865-0451 at USC Norris can give you more information and answer your questions.  Here are answers to some Frequently Asked Questions about clinical trials at USC Norris.

Call the Colorectal Cancer Coalition Answer Line for more help with understanding these trials or finding other clinical trials to meet your needs. 877-4CRC-111 (877-427-2111).

Update: View a video from Dr. Lenz about the drug’s development:

USC Norris Comprehensive Cancer Center and Hospital: Beyond the Fight from Ryan Ball on Vimeo.