Exploring the Effectiveness of an Experimental Class of Drug

Lily Yang, M.D., Ph.D., and Hui Mao, Ph.D., National Cancer Institute, National Institutes of Health

Does adding a novel drug to standard treatment help control the spread of advanced pancreatic cancer in patients with the BRCA mutation?

A clinical trial takes a closer look at this question, using standard chemotherapy drugs given for metastasized pancreatic cancer and adding a new class of drug called PARP inhibitors. This trial is for patients who carry the BRCA mutation or the related PALB2 mutation.

Comparing Drug Combinations

In this trial participants will be randomly selected to receive either gemcitabine and cisplatin or gemcitabine and cisplatin plus veliparib, a PARP inhibitor. A third group will receive only the experimental veliparib, for a short time. Researchers are comparing the effectiveness of the chemotherapy combinations in the study.

Gemcitabine is converted into two metabolites that cause cell death. One reduces the number of proteins available to make DNA; the other shortens the DNA strands. Cisplatin is a platinum-based drug that disrupts DNA and kills cancer cells.

How PARP Inhibitors Work

The PARP enzyme is important in repairing small breaks in single DNA strands. Drugs that block the action of PARP—inhibitors like veliparib, the drug in this study—make the enzyme less effective at repairing the small breaks. When the DNA makes copies of itself, or replicates, these breaks in the strands are also copied, causing the cell to die. Cancer cells replicate their DNA more often than normal cells, which is why PARP inhibitors can be an effective part of cancer treatment.

These mutations are mostly inherited, and most common in Ashkenazi Jews, Norwegian, Dutch, and Icelandic people. BRCA1 and BRCA2 genes normally function as tumor suppressor proteins and these genes make sure that damaged DNA is repaired properly. When the BRCA genes are mutated, DNA does not get repaired properly, leading to more mutations and increasing the likelihood of developing cancer. The PALB2 gene works closely with the BRCA2 gene. People carrying these mutations are at increased risk of developing breast, ovarian, and particularly pancreatic cancer for those carrying the PALB2 mutation.

Because the DNA of BRCA and PALB2 carriers does not get properly repaired, PARP inhibitors may work particularly well on their cancers.

We encourage you to consult your physicians for clinical trials that may be right for you. The website ClinicalTrials.gov provides more details about this trial as well as many others. You can visit the Let’s Win Trial Finder for a listing of all active pancreatic cancer clinical trials.

This trial remains active but is no longer recruiting patients. Read about more trials for people who have BRCA and other mutations.

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