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Combining Chemotherapy and a PARP Inhibitor for Advanced Solid Tumors

Name of the Trial

Phase I Study of PARP Inhibitor AZD2281 in Combination with Cisplatin and Gemcitabine Hydrochloride in Patients with Unresectable or Metastatic Solid Tumors (NCI-08-C-0128). See the protocol summary.

Principal Investigator

Dr. Giuseppe Giaccone
Dr. Giuseppe Giaccone
Principal Investigator

Dr. Giuseppe Giaccone, NCI Center for Cancer Research

Why This Trial Is Important

Over the past decade, new drugs and biological agents have been developed that fight cancer by targeting certain proteins thought to be involved in promoting cancer cell growth and survival. These new treatments are commonly referred to as targeted therapies. In contrast, traditional chemotherapy drugs and radiation therapy attack cancer by preferentially killing rapidly dividing cells.

AZD2281 (olaparib) is a new type of targeted therapy that blocks the activity of proteins called PARP1 and PARP2, which help cells repair damaged DNA. Researchers hope that combining a PARP inhibitor like AZD2281 with traditional chemotherapy drugs, which work by damaging DNA, will produce greater anticancer effects than either chemotherapy or a PARP inhibitor alone. This approach is based on the observation that cells are unable to survive if they accumulate high levels of DNA damage.

In this clinical trial, patients who have solid tumors that cannot be removed by surgery or that have spread to other areas of the body will be treated with AZD2281 and the chemotherapy drugs cisplatin and gemcitabine. Doctors will assess the safety of this regimen, determine the maximum tolerated dose, and examine the effects of treatment on specific molecular markers in tumor biopsy specimens and blood samples taken from the patients.

"Preclinical models show synergy between PARP inhibitors and drugs that work by damaging DNA," said Dr. Giaccone. "Non-small cell lung, bladder, and pancreatic cancers may be particularly interesting cancers in which to study this regimen, because the combination of cisplatin and gemcitabine is already used as a standard treatment in these tumor types.

"In previous clinical studies, olaparib [AZD2281] has demonstrated antitumor activity as a single agent against some breast, ovarian, and prostate cancers associated with BRCA1 or BRCA2 gene mutations," continued Dr. Giaccone. "Many of the patients in those studies experienced clinical benefit without substantial adverse effects."

For More Information

See the lists of entry criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

  • Posted: November 3, 2009