Adaptive ChemoTherapy for Ovarian Cancer
Adaptive ChemoTherapy for Ovarian cancer: A multicentre phase II randomised controlled trial to evaluate the efficacy of Adaptive Therapy (AT) with carboplatin, based on changes in CA125, in patients with relapsed platinum-sensitive high grade serous or high grade endometrioid ovarian cancer (ACTOv)
- Gynaecological cancer
Why this trial?
This trial aims to investigate a new personalised treatment approach for ovarian cancer that has returned after previous chemotherapy.
The main treatment strategy for ovarian cancer, which is diagnosed in around 7,500 women each year in the UK, consists of a combination of surgery and chemotherapy. The aim of chemotherapy is to kill as many cells as possible using the highest dose of drug that does not cause unacceptable side effects in the patient (known as the maximum tolerated dose).
Although this approach can be effective at reducing the size of the tumour initially, with repeated administration, any cancer cells that are resistant to the drug will still be able to grow. These resistant cells drive cancer recurrence, generating a tumour that is no longer responsive to chemotherapy (therapy resistance). Overcoming therapy resistance in ovarian cancer, while also limiting the side effects in patients caused by high doses of chemotherapy, is a key challenge.
The treatment approach in this trial, known as adaptive therapy, aims to prevent the development of drug resistance by fine-tuning the treatment dose given to each individual patient as their tumour evolves over time in response to therapy.
This research is important because it could provide a new, highly personalised therapeutic strategy for women with incurable ovarian cancer, that could prolong patient survival while giving a lower drug dose each time.
Why this intervention?
Resistant cancer cells cannot grow as well when they are competing with non-resistant (sensitive) cancer cells present in the tumour. Wiping out all sensitive cancer cells with high dose chemotherapy removes the competition for the resistant ones, allowing their numbers to expand.
The treatment approach used here is known as adaptive therapy. Instead of trying to kill as many cancer cells as possible, the goal of adaptive therapy is to maintain a small population of cells that are sensitive to chemotherapy throughout a patient’s treatment. This could be achieved by using smaller drug doses of chemotherapy and adjusting the dose accordingly as a patient’s tumour shrinks or grows. The sensitive cells that remain, suppress the growth of the resistant cells, offering a long-term strategy to control the tumour and preserve sensitivity to the same drug.
ACTOv is a phase II two-arm randomised trial, that will include 80 patients with high-grade serous and endometrioid ovarian cancer, across nine hospitals in the UK. Half of the patients will receive six cycles of the standard dose of a chemotherapy (carboplatin), while the other half will receive an adaptive therapy regimen of carboplatin, meaning the dose of carboplatin will be adapted during treatment: after each cycle, patients will have a blood test to see if their tumour has shrunk. If this is the case; the carboplatin dose will be reduced. If their tumour has grown, the carboplatin dose will be increased. By adjusting the chemotherapy dose in this way, the team hopes to preserve sensitivity to carboplatin, while reducing the treatment dose required and associated side effects.
- Dr. Michelle Lockley, Barts Cancer Institute, London, United Kingdom (Chief Investigator)
- University College London
- Barts Charity
More info: NCT05080556
Hoare, J., et al., Platinum resistance induces diverse evolutionary trajectories in high grade serous ovarian cancer. BioRxiv, 2019. https://www.biorxiv.org/content/10.1101/2020.07.23.200378v1.
Author: Kristine Beckers (Trial Manager)
Last updated: February 2023