Trial Details

Trial status:

Active (recruiting)

Recruitment start date:

10/03/2023

Funder:

Sponsor:

UCL

Chief Investigator:

Professor Michelle Lockley

Recruitment target:

EudraCT number:

2021-003412-40

Contact details:

ctc.ACTOv@ucl.ac.uk

Note: For enquiries only. DO NOT use for clinical referrals.

ACTOv

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

Description

Design:

ACTOv is a multicentre, phase II randomised controlled trial to evaluate Adaptive Therapy (AT) with carboplatin in women with relapsed platinum-sensitive high grade serous or high grade endometrioid cancer of the ovary, fallopian tube and peritoneum, whose disease has progressed on or more than 6 months after day 1 of the last cycle of platinum-based chemotherapy.

Adaptive Therapy (AT) is a new treatment paradigm that prescribes dose reductions and ‘drug holidays’ to overcome drug resistance by allowing fitter, drug-sensitive cells to grow back, and suppress the emergence of drug-resistant cells, and therefore, re-sensitise the tumour to the next round of treatment. ACTOv will test this strategy for the first time with carboplatin in women with relapsed ovarian cancer by comparing standard carboplatin treatment (Arm 1) to carboplatin Adaptive Therapy (Arm 2).

Treatment:

All patients will attend 3-weekly for pre-treatment blood tests including CA125 and research bloods, prior to consultation with their clinical team as per standard of care (SOC). Patients will be randomised in a 1:1 ratio between Arms 1 and 2:

Arm 1: Standard Treatment - Carboplatin AUC5 - based on absolute nuclear medicine glomerular filtration rate (NM GFR).
Arm 2: Adaptive Therapy - Carboplatin AUC dosing based on changes in serum CA125 (a proxy measure of total tumour burden, indicating a patient’s own tumour response to the last round of chemotherapy). Briefly, when CA125 declines by >25%, dose is reduced at the next cycle and when CA125 increases by >25%, dose at the next treatment cycle is increased.

Treatment in both arms will be administered intravenously (IV) every 21 days (q21D), and for a maximum of 6 cycles in Arm 1; and 12 cycles in Arm 2. The starting carboplatin dose in both Arms and maximum carboplatin dose is AUC5 according to absolute nuclear medicine glomerular filtration rate. This is the maximum carboplatin dose in both arms regardless of CA125.

After completion of treatment, there will be 6-weekly surveillance visits up to Week 40; which will then be followed by 12-weekly follow up visits up to Week 82.

Key inclusion/exclusion criteria:

Patients must have histologically proven diagnosis of high grade serous or high grade endometrioid carcinoma of the ovary, fallopian tube or peritoneum and must have responded to their most recent platinum treatment by CT or MRI or by GCIG CA125 response criteria. Their pre-trial CT or MRI-confirmed disease progression should be ≥ 6 months after day 1 of the last cycle of platinum-containing chemotherapy (cisplatin or carboplatin) and patients should require treatment with further platinum-based chemotherapy. Patients should have measurable disease by RECIST v1.1 on a CT scan conducted within 28 days prior to randomisation (patients with non-measurable disease could be eligible if they meet GCIG CA125 progression criteria), and CA125 should be ≥ 100iU/l at screening. Patients must be deemed fit to receive carboplatin and have an adequate renal, liver and bone marrow function.

Patients with non-epithelial ovarian cancer, carcinosarcoma, low-grade serous and endometrioid carcinomas, mucinous & clear-cell carcinomas would not be eligible, as well as patients requiring treatment with combination chemotherapy regimens. Patients would also be ineligible if they had any malignancy treated within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, Stage 1, grade 1 endometrial carcinoma.

Duration of recruitment:

Anticipated 3 year recruitment period.

Aim

The overall aim of the ACTOv trial is to evaluate the efficacy, acceptability, deliverability, compliance, and safety of Adaptive Therapy (AT) with carboplatin, based on changes in CA125, in patients with platinum-sensitive, relapsed high grade serous or high grade endometrioid carcinoma of the ovary, fallopian tube or peritoneum, progressing on or more than 6 months after day 1 of the last cycle of platinum-based chemotherapy.

Contact the trial team

View trial documents

Cancer Research UK & UCL Cancer Trials Centre
University College London
90 Tottenham Court Road
London
W1T 4TJ

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Email:
ctc.enquiries@ucl.ac.uk
Telephone:
+44 (0)20 7679 9898 (General CTC Enquiries)
Fax:
020 7679 9899

CTC staff

University College London, Gower Street, London, WC1E 6BT +44 (0)20 7679 2000