Brief Title
Adaptive ChemoTherapy for Ovarian Cancer in Patients With Replased Platinum-sensitive High Grade Serous or High Grade Endometrioid Ovarian Cancer
Official Title
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
Brief Summary
ACTOv will compare standard 3-weekly carboplatin (AUC5), to carboplatin delivered according
to an AT regimen. The AT regimen will modify carboplatin dose according to changes in the
clinical-standard serum biomarker CA125 as a proxy measure of total tumour burden and an
individual patient's response to the most recent chemotherapy treatment. AT could prolong
sensitivity to carboplatin and extend tumour control, while simultaneously reducing
chemotherapy dose and drug-induced toxicity. Carboplatin is a low cost and low toxicity drug
that has an enduring and central role in ovarian cancer treatment.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Modified Progression Free Survival (mPFS)
Secondary Outcome
Acceptability (1/2)
Condition
Ovarian Cancer
Intervention
Carboplatin
Study Arms / Comparison Groups
Arm 1 (control) - standard dosing carboplatin
Description: Arm 1 (Standard Dosing): Carboplatin AUC5 based on nuclear medicine renal clearance.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
80
Start Date
November 1, 2022
Completion Date
November 1, 2027
Primary Completion Date
November 1, 2026
Eligibility Criteria
Inclusion Criteria:
1. Female patients aged ≥18 years
2. ECOG performance status 0-2
3. Histologically proven diagnosis of high grade serous or high grade endometrioid
carcinoma of the ovary, fallopian tube or peritoneum
4. Most recent regimen must have included platinum (cisplatin or carboplatin)
5. Must have previously received a PARP inhibitor
6. 6. Must have responded to most recent platinum treatment by CT or MRI or by GCIG CA125
response criteria
7. Pre-trial CT or MRI-confirmed disease relapse ≥ 6 months after day 1 of the last cycle
of platinum-containing chemotherapy (cisplatin or carboplatin) and requiring treatment
with further platinum-based chemotherapy
8. Measurable disease by RECIST v1.1 on a CT scan conducted within 28 days prior to
randomisation (Patient with non-measurable disease could be eligible if they meet GCIG
CA125 progression criteria)
9. CA125 ≥ 100iU/l at screening
10. Agree to provide additional research blood samples at the same time as blood draws
prior to each carboplatin treatment, 6-weekly during surveillance and at 12- weekly
follow-up visit
11. Expected to be able to commence treatment within 28 days post randomisation
12. Adequate bone marrow function
13. Adequate liver function
14. Adequate renal function
15. Postmenopausal or women of child-bearing potential (WOCBP) must agree to have an urine
or serum pregnancy test at screening for evidence of non-childbearing status and prior
to trial treatment and use adequate contraception for duration of trial
16. Willing and able to give consent and able to comply with treatment and follow up
schedule
Exclusion Criteria:
1. Non-epithelial ovarian cancer, carcinosarcoma, low-grade serous and endometrioid
carcinomas, mucinous & clear-cell carcinomas
2. Patients requiring treatment with combination chemotherapy regimens
3. Patients with a known hypersensitivity to carboplatin
4. Persisting ≥ grade 2 CTCAE v5 adverse events/ toxicity (except alopecia and
neuropathy) from previous anti-cancer treatment.
5. Treatment with any other investigational agent, or participation in another
interventional clinical trial within 28 days prior to randomisation.
6. Major surgery within 14 days before anticipated start of treatment and patients must
have recovered from any effects of major surgery.
7. Evidence of any other disease, metabolic dysfunction, physical examination finding or
laboratory finding giving reasonable suspicion of a disease or condition that
contra-indicated the use of an investigation drug or puts the patients at high risk
for treatment-related complications.
8. Other psychological, psychiatric, social or medical condition, physical examination
finding or a laboratory abnormality that the Investigator considers would make the
patient a poor trial candidate or could interfere with protocol compliance or the
interpretation of trial results.
9. 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.
10. Patients with symptomatic uncontrolled brain or meningeal metastases. A scan to
confirm the absence of brain metastases is not required. The patient can receive a
stable dose of corticosteroids before and during the study as long as these were
started at least 4 weeks prior to treatment.
11. Patients with spinal cord compression unless considered to have received definitive
treatment for this and evidence of clinically stable disease for 28 days prior to
randomisation.
12. Pregnant or breast-feeding women are excluded. Women of childbearing potential will be
excluded unless effective methods of contraception are used from signing of the
informed consent, throughout the period of taking study treatment and for at least 6
months after last dose of trial drug(s).
13. Inability to attend or comply with treatment or follow-up scheduling.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 02076794466, [email protected]
Administrative Informations
NCT ID
NCT05080556
Organization ID
136618
Responsible Party
Sponsor
Study Sponsor
University College, London
Study Sponsor
, ,
Verification Date
October 2022