Testing Treatment Combinations to Make Surgery More Effective

Can an immunotherapy drug and one that used to treat high blood pressure increase the effectiveness of standard treatment and immunotherapy for pancreatic tumors that may qualify for surgical removal?

Researchers are looking at different combinations of a standard protocol of chemotherapy and radiation to see if the blood pressure drug can improve the standard protocol and possibly make immunotherapy work better.

The Standard Treatments

FOLFIRINOX is one of the standard treatments for advanced pancreatic cancer. It is a four-drug combination: FOL (leucovorin calcium, or folinic acid), F (fluorouracil, or 5-FU), IRIN (irinotecan hydrochloride), OX (oxaliplatin). Each of these drugs enhances the action of the others. Fluorouracil (5-FU) is an antimetabolite that disrupts a specific part of the cell replication cycle. Derived from folic acid, leucovorin enhances the effects of 5-FU. Irinotecan inhibits the replication and transcription of DNA, and so interferes with cell growth. Oxaliplatin, a platinum compound, disrupts DNA and kills cancer cells. Modified FOLFIRINOX varies the dose or form of the different drugs that make up the combination.

Stereotactic body radiation therapy, known as SBRT, uses multiple beams of high-dose radiation focused on a specified location in the body. The technique enables the radiation oncologist to kill cancer cells in a defined location, limiting the exposure of healthy tissue to radiation. The precise location for the radiation beams is determined using 4-D imaging to map the area that will receive treatment. Metal markers are then implanted to outline the boundaries of that area.

The Experimental Additions

Losartan is a drug used for high blood pressure. Research has shown that cancer patients who received losartan as part of (or in addition to) their treatment plan tend to survive longer than other patients receiving the same treatments. It has been found to improve the delivery of chemotherapy drugs to the tumor.

One of the ways cancer cells evade the immune system is by producing proteins that tell the T cells of the immune system not to attack the tumor. Nivolumab (brand name Opdivo) is an immune checkpoint blockade drug that works by reactivating T cells to attack the tumor.

Testing Combinations

Participants are randomly assigned to one of four different groups.

• One group will receive a standard protocol of FOLFIRINOX followed by SBRT prior to surgery to remove the tumor.
• A second group will receive FOLFIRINOX and losartan, SBRT, and then surgery.
• A third group will have FOLFIRINOX and losartan, then SBRT and nivolumab at the same time, followed by surgery.
• The final group will get FOLFIRINOX followed by SBRT and nivolumab, and then surgery.

The researchers are looking for no sign of cancer cells at the edges where the tumor was removed, and at overall survival.

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 is active but no longer recruiting.

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