Adaptive ChemoTherapy for Ovarian Cancer in Patients With Replased Platinum-sensitive High Grade Serous or High Grade Endometrioid Ovarian Cancer

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Carboplatin
  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.

Первичные конечные точки

• Modified Progression Free Survival (mPFS) [Срок оценки: From the date of randomisation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 years.]

Вторичные конечные точки (12)

• Acceptability (1/2) [Срок оценки: From the date of randomisation to the first dose of treatment (within 28 days from randomisation)received by patient. Measured as the number of patients approached who accept randomisation.]
• Acceptability (2/2) [Срок оценки: From the date of randomisation to the first dose of treatment (within 28 days from randomisation)received by patient. Measured as the percent of patients approached who accept randomisation.]
• Deliverability (1/2) [Срок оценки: Measured as the number of treatment cycles that are delivered as per protocol, described by trial arm (maximum of 6 cycles in control arm and 12 in experimental arm, approx.. 18 weeks and 36 weeks respectively). Treatment delays, reductions and omissions]
• Deliverability (2/2) [Срок оценки: Measured as the number of treatment cycles that are delivered as per protocol, described by trial arm (maximum of 6 cycles in control arm and 12 in experimental arm, approx.. 18 weeks and 36 weeks respectively). Treatment delays, reductions and omissions]
• Compliance [Срок оценки: Total cumulative carboplatin dose will be calculated for each patient over time on treatment (max. of 6 cycles in control arm and 12 cycles in experimental arm, approximately 18 weeks and 36 weeks respectively]
• Adverse events (1/2) [Срок оценки: Adverse events will be reported between informed consent and 30 calendar days post last IMP (i.e. max. of 6 cycles in control arm and 12 cycles in experimental arm, approximately 30 days after 18 weeks or 36 weeks respectively)]
• Adverse events (2/2) [Срок оценки: Adverse events will be reported between informed consent and 30 calendar days post last IMP (i.e. max. of 6 cycles in control arm and 12 cycles in experimental arm, approximately 30 days after 18 weeks or 36 weeks respectively)]
• Quality of life (1/2) - EORTC questionnaire (assessing the quality of life of patients with ovarian cancer) [Срок оценки: At baseline, during treatment and follow up until the first documented progression or date of death (estimate 6 or 12 months but can be up to 4 years)]
• Quality of life (2/2) - EQ-5D ((mobility, self-care, usual activities, pain/discomfort, anxiety/depression, a single summary index and a visual analogue scale) [Срок оценки: At baseline, during treatment and follow up until the first documented progression or date of death (estimate 6 or 12 months but can be up to 4 years)]
• Fear of progression [Срок оценки: At baseline, during treatment and follow up until the first documented progression or date of death (estimate 6 or 12 months but can be up to 4 years)]
• CA125 [Срок оценки: Measured at baseline, 3 weekly during treatment, 6-weekly during surveillance and 12-weekly during follow-up, through study completion, an average of 1 year.]
• Further treatment (1/3) [Срок оценки: Additional treatment of patients who progress will be described by trial arm, this will include the time-to-next treatment (measured from randomisation).]

Критерии участия

Критерии включения

• Female patients aged ≥18 years
• ECOG performance status 0-2
• Histologically proven diagnosis of high grade serous or high grade endometrioid carcinoma of the ovary, fallopian tube or peritoneum
• Most recent regimen must have included platinum (cisplatin or carboplatin)
• Must have previously received a PARP inhibitor
• 6\. Must have responded to most recent platinum treatment by CT or MRI or by GCIG CA125 response criteria
• 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
• 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)
• CA125 ≥ 100iU/l at screening
• 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
• Expected to be able to commence treatment within 28 days post randomisation
• Adequate bone marrow function
• Adequate liver function
• Adequate renal function
• 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
• Willing and able to give consent and able to comply with treatment and follow up schedule

Критерии исключения

• Non-epithelial ovarian cancer, carcinosarcoma, low-grade serous and endometrioid carcinomas, mucinous \& clear-cell carcinomas
• Patients requiring treatment with combination chemotherapy regimens
• Patients with a known hypersensitivity to carboplatin
• Persisting ≥ grade 2 CTCAE v5 adverse events/ toxicity (except alopecia and neuropathy) from previous anti-cancer treatment.
• Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to randomisation.
• Major surgery within 14 days before anticipated start of treatment and patients must have recovered from any effects of major surgery.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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).
• Inability to attend or comply with treatment or follow-up scheduling.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Великобритания · 1 центр

• University College London Hospitals — London

Публикации

• Mukherjee UA, Hockings H, Counsell N, Patel A, Narayanan P, Wilkinson K, Dhanda H, Robinson K, McNeish I, Anderson ARA, Miller R, Gourley C, Graham T, Lockley M. Study protocol for Adaptive ChemoTherapy for Ovarian cancer (ACTOv): 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 relaps PMID 39806715

Идентификаторы

NCT: NCT05080556 · 136618

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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