An open-label, randomised, phase I/II trial of rucaparib combined with nivolumab +/- ipilimumab to augment response in homologous repair deficient patients with relapsed ovarian, primary peritoneal and fallopian tube cancer
Who can take part
Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.
You may be able to take part in this clinical trial if you:
- are aged 16 years or older
- have high-grade serous or grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer
- have had one or more than one round of chemotherapy containing a platinum-based drug (carboplatin or cisplatin)
- have had three or less rounds of chemotherapy in total
- have not received any previous PARP inhibitors, anti-PD-1 or anti-PDL-1 or CTLA4 therapy
- had treatment for your cancer between 3–12 months ago
- had platinum-based chemo between 3–12 months ago
- have a germline or somatic BRCA1 or BRCA2 gene mutation OR
- have normal BRCA genes but show Loss of Heterozygosity (LoH) in your tumour genes. Loss of Heterozygosity is a scoring system used when analysing tumour tissue to reflect how much scarring is present in the genes of that tissue
You may also be able to participate in the trial if you have any high-grade ovarian cancer histology other than the types mentioned. This is only possible if you are already known to have a germline or somatic BRCA1/2 mutation.
This is not an exhaustive list. If you're interested in participating in a clinical trial, you should speak to your doctor about what other criteria might apply.
About the trial
The purpose of this trial is to find out how safe and effective it is to have either one or two immunotherapy drugs alongside the parp inhibitor Rucaparib. Researchers want to find out if using the different combination of drugs will prolong the time it takes for your cancer to come back compared with being treated with Rucaparib on its own.
The drugs involved in this trial are:
- Rucaparib – a PARP inhibitor. This is a tablet taken by mouth.
- Nivolumab – an antibody, which blocks a receptor called Programme Death Receptor-1 (PD-1) on the surface of your T cells (immune fighting cells). By blocking these receptors, the antibodies are thought to help your immune system fight cancer cells. It's been approved and licensed in the UK for standard use in lung cancer, advanced melanoma and kidney cancer. Nivolumab is given intravenously (through a vein).
- Ipilimumab – an antibody which blocks a different receptor called Cytotoxic T-Lymphocyte Antigen-4 (CTLA4) on the surface of T cells (immune fighting cells). By blocking these receptors, the antibodies help your immune system to fight your cancer cells. Ipilimumab has been used in the treatment of more than 19,000 patients. It's been approved and licensed in the UK for standard use in patients with advanced melanoma. Ipilimumab is given intravenously (through a vein).
Researchers are testing these drugs in women who either:
- have a mutation in their BRCA 1 or 2 genes
- have normal BRCA genes but they show Loss of Heterozygosity (LoH) in their tumour genes
Loss of heterozygosity is a scoring system applied to tumour tissue to reflect how much scarring is present in the genes of that tissue. One of the drugs used in this study, rucaparib, has been shown to prolong the remission of those patients carrying the BRCA1 and 2 genetic mutations. Rucaparib also prolongs remission in patients with normal BRCA and a high LoH score, but not generally for as long as it can for women with BRCA1 and 2 gene mutations.
If you take part in this study, you'll be randomised (placed into a treatment group by a computer) into one of three treatment groups:
- Rucaparib only – you'll take oral rucaparib twice every day.
- Rucaparib with Nivolumab (RN) – you'll take oral rucaparib twice every day and will also receive an intravenous drip of nivolumab every two weeks for a maximum of one year.
- Rucaparib with Nivolumab and Ipilimumab (RNI) – you'll take oral rucaparib twice every day and will also receive an intravenous drip of nivolumab every two weeks for a maximum of one year and an intravenous drip of ipilimumab every six weeks for a maximum of one year.
If you take part in this study, you'll also need to:
- have some additional tests to monitor for side effects of treatment.
- donate additional blood samples for research purposes.
- have an additional tumour biopsy before treatment starts and again when treatment ends (if safe and feasible to do so).