US-based biopharmaceutical firm Clovis Oncology (CLVS) has started dosing first patient in a Phase II trial of its oral, potent, small molecule poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib to treat ovarian cancer patients.
The trial, also called as ARIEL2, is being conducted at a US study site to assess rucaparib, which is being developed for the treatment of platinum sensitive, relapsed ovarian cancer.
According to the company, PARP inhibitors have the potential to provide meaningful clinical benefit to many women with ovarian cancer.
University of Glasgow Institute of Cancer Sciences professor of gynecological oncology Iain Mcneish said it is found that there are many ovarian cancer patients who do not carry germline BRCA mutations yet still benefit from PARP inhibitor therapy.
"This study is designed specifically to help identify these women using tumour DNA sequencing, which is a viable approach since nearly all ovarian cancer patients have plentiful tumour tissue samples following de-bulking surgery," Mcneish said.
"Platinum sensitivity alone may not be the best predictor of PARP inhibitor outcome and I am confident we can do much better for patients using tumour genetic analysis."
ARIEL2 trial is aimed at identifying tumour characteristics that predict sensitivity to rucaparib using DNA sequencing to evaluate each patient’s tumour.
Tumour samples of patients secured from the study will be tested for BRCA1 and BRCA2 mutations, as well as other biomarkers that are expected to confer sensitivity to PARP inhibitor therapy.
The company said all patients in the trial will receive both rucaparib and their molecular test results including tumour BRCA status, and will also be treated until their disease progresses or until they withdraw from the trial.
The company expects to start a randomised, double-blind Phase III trial called ARIEL3 by the end of 2013, under which effects of rucaparib will be compared with placebo.
ARIEL3 study will assess whether rucaparib in platinum-sensitive, ovarian, fallopian tube or primary peritoneal high-grade cancer patients can extend the period of time for which the disease is controlled.
The study will also determine whether a patient’s BRCA mutation status or other biomarkers predict their response to rucaparib.
If the trial is successful, Clovis expects to use the data generated from the ARIEL studies to file an application with the US Food and Drug Administration (FDA) and other health authorities requesting an approval for rucaparib in all genetically-appropriate patients with relapsed, platinum-sensitive ovarian, fallopian tube or primary peritoneal high-grade cancer in a maintenance setting.
Rucaparib, which is administered orally, is under development for the treatment of advanced solid tumours, epithelial ovarian, fallopian tube, primary peritoneal cancer and an adjuvant treatment for high-risk germ-line BRCA-defective breast cancer and triple-negative breast cancer.
Image: An ovarian cancer as seen on CT. Photo: courtesy of Jmh649.