AKTivate

Randomised Phase II open-label window of opportunity trial AKTivate – Identifying target engagement and biomarkers of response, including an imaging biomarker, in participants receiving capivasertib plus exemestane and capivasertib alone in post-menopausal participants with oestrogen receptor positive (ER+) early-stage breast cancer.

Research summary

Breast cancer is the most common cancer in UK women. Medical imaging like mammography (taking X-ray pictures) and ultrasound (using sound waves) are used to track changes in size of tumour over time. Unfortunately, It can take many weeks before changes large enough to tell if treatments are working are seen. 

Tumour cells act differently to regular cells. Some of these differences can be used to get an earlier look at whether a treatment is working. Knowing a treatment isn't working early on allows for quicker adjustments, increasing the chance of a good outcome and reducing the time patients suffer with side effects from ineffective treatments.

One thing that sets the cells apart is how they use sugar. Tumour cells take in more sugar from the blood and use it in a unique way. This leads to many types of tumours having lots of a natural substance called lactate.

In this proposed trial, ACTivate , we will use a new type of imaging called Hyperpolarised C13 Magnetic Resonance Imaging (MRI). This allows us to see lactate build-up in breast cancers. If a drug treatment is working well, the amount of lactate should fall. This usually happens at an earlier stage than changes in size.

60 women with early-stage oestrogen-positive (ER+) breast cancer will participate. These women will have Hyperpolarised C13 MRI scans and cancer biopsies before and after 2 weeks of treatment in what we call a window of opportunity trial. All women will receive the drug capivasertib. Capivasertip has worked well in trials for advanced and metastatic breast cancer. AKTivate will gather information to help assess if it might exemestane. This is commonly used in early and advanced ER+ breast Cancer. AKTivate will assess if hyperpolarized C13 MRI can reliably assess whether capivasertib and exemestane are working within just 2 weeks. 

Funding is through a collaboration with AZ.

Main inclusion criteria

  • Female sex as assigned at birth
  • Aged between 18 and 79 years
  • Post-menopausal
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • ER-positive, HER2-negative invasive breast cancer
  • Intermediate or high-risk of breast cancer recurrence (grade 2or 3 and Ki67≥10%)
  • Clinical stage T1c-4, NX or N0-N3, M0 (primary breast cancer≥15 mm)
  • Adequate bone marrow, renal and hepatic function
  • Capable of giving written informed consent

Main exclusion criteria

  • Metastatic, inoperable locally advanced or recurrent disease
  • History of another primary malignancy except for malignancy treated with curative intent
  • Persistent toxicities caused by previous anticancer therapy, excluding alopecia
  • Diabetes mellitus type 1
  • Diabetes mellitus type 2
  • Haemoglobin ≥ 7.0% at screening
  • Some cardiac conditions as: mean resting QT interval at screening, arrhythmia, medications that required discontinuation of that medication, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives
  • Hypotension at screening
  • Known HIV infection that is not well controlled  
  • Known active hepatitis B or C infection
  • Known active tuberculosis infection
  • Known contraindication or inability to tolerate MRI
  • Known hypersensitivity or contraindications to aromatase inhibitors, capivasertib or any of the excipients of exemestane or capivasertib
  • Received any prior treatment for either this breast cancer or a previous breast cancer diagnosis
  • Prior exposure to any chemotherapy or anti-cancer agents without appropriate washout period before randomization/enrolment
  • Hormone therapy including hormone replacement therapy (HRT) use in 6 months prior screening
  • Radiotherapy within 14 days prior to the first dose of study intervention
  • Major surgical procedure or significant traumatic injury within 28 days of the first dose of capivasertib
  • Previous treatment in the AKTivate study
  • Participation in another clinical study with a study intervention or investigational medicinal device administrated in the 28 days prior to first dose of study intervention or concurrent enrolment in another clinical study 
  • Women of childbearing potential, women who are currently pregnant or breastfeeding, women who are planning to become pregnant or women who are lactating during the study period
  • Judgement by the investigator that the participants should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements
  • Body mass index < 18.5 at the time of screening

Funders and sponsors

Chief investigator

Chief Investigator: Prof Jean Abraham

Contact details

Clinical Trials Coordinator: Giovanni Distefano & Silvia Tarantino
Email: [email protected]