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Combining Chemotherapy and a PARP Inhibitor for Advanced Solid Tumors
Untitled Document
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
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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.
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