A multi-center, phase II clinical trial is seeking women with invasive triple-negative breast cancer or known BRCA1/2 mutation who have HER2 negative disease. Participants, who have stages I-III breast cancer, must have received neoadjuvant (pre-surgical) chemotherapy that did not eliminate the cancer.
The study will evaluate women treated with cisplatin, a platinum-based chemotherapy medicine, and those treated with a combination of cisplatin and rucaparib, a PARP inhibitor. The two groups will be compared for the percentage of women who do not have a recurrence of breast cancer within two years.
With a phase II trial, primary goals include testing treatment effectiveness, safety and side effects.
Reason for the Study
Researchers are investigating treatments for cancers that do not respond well to chemotherapy. Chemotherapy is a highly effective treatment for triple-negative breast cancers and for some cancers caused by defects in the BRCA1/2 genes. Platinum-based medicines, although still in clinical trials, appear to work well against these types of breast cancers. They kill cancer cells by damaging DNA (the instructions that tell cells when and how to grow).
Because cancer cells, like healthy cells, can repair some damaged DNA, chemotherapy sometimes stops working. This happens when cancer cells repair themselves before the medicine can kill them. PARP inhibitors block enzymes in cancer cells that help them repair damaged DNA. When cancer cells cannot repair DNA after treatment, they eventually shrink or die.
Cisplatin and rucaparib were chosen for this study because platinum medicines and PARP inhibitors both impact the type of cancer cells that are more common in triple-negative and BRCA-related cancers.
Goals of the Trial
The primary goal of this trial is to assess two-year disease-free survival (no recurrence within 2 years) in women with triple-negative, BRCA1/2 mutation breast cancer treated with cisplatin and rucaparib in combination, and those treated with cisplatin alone.
Researchers will also consider one-year disease-free and five-year overall survival, collect information about participants’ reaction to rucaparib, comparing it to other rucaparib trials, and look at relationships among PARP inhibition, recurrence and side effects. I think it is fine to include these endpoints here.
Structure of the Trial
The trial will randomly assign 135 women from 25 different study sites to one of two treatment arms. One group will get cisplatin intravenously (by vein) alone, four times once every three weeks. The other group will get cisplatin and rucaparib, also by vein, in combination four times once every three weeks, followed by weekly rucaparib for 24 weeks.
The trial is open label, which means both researchers and participants know who is getting which treatment.
Am I Eligible?
You may be eligible for this study if you have triple-negative breast cancer that was stage I, II or III at diagnosis. If the cancer is estrogen- or progesterone-receptor positive, you may be able to enroll if you also have a confirmed BRCA1/2 mutation. You may not enroll if the cancer is HER2 positive, no matter what your BRCA status.
You must also have had significant residual invasive cancer after neoadjuvant chemotherapy. The chemotherapy treatment you received must have been with an anthracycline or taxane, or both, and cannot have included cisplatin. Your surgery and postoperative radiation, if given, must have been completed at least 14 days before registration. If you had lumpectomy, whole breast radiation is required.
You must be willing to use of contraception from the time of registration until four weeks after the study is over, and you must not be pregnant or breastfeeding.
What Else Do I Need to Know?
Common side effects of cisplatin include nausea, vomiting, diarrhea, loss of taste, hair loss, hiccups and dehydration. Kidney failure and hearing loss are more serious possible side effects.
For contact information, visit the trial’s website.