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

April 11, 2024 updated by: University College, London

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 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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm 1 (control) - standard dosing carboplatin
Arm 1 (Standard Dosing): Carboplatin AUC5 based on nuclear medicine renal clearance.
Drug: 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.
Experimental: Arm 2 (experimental) - adaptive therapy carboplatin according to CA125
Arm 2 (Adaptive Therapy): Carboplatin dose will be calculated according to the CA125 value.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modified Progression Free Survival (mPFS)
Time Frame: 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.
Measured from the date of randomisation to the date of objective progression (investigator assessed using RECIST v1.1) but comparing CT scans to the baseline CT rather than the radiological nadir), clinical progression or death from any cause (in the absence of progression)
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.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acceptability (1/2)
Time Frame: 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.
the number of eligible patients approached who accept randomisation and continue to receive treatment
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)
Time Frame: 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.
the proportion of eligible patients approached who accept randomisation and continue to receive treatment
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)
Time Frame: 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
the number of treatment cycles that are delivered as per protocol, described by trial arm
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)
Time Frame: 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
the proportion of treatment cycles that are delivered as per protocol, described by trial arm
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
Time Frame: 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
total cumulative carboplatin dose will be calculated for each patient over time on treatment, and described by trial arm
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)
Time Frame: 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 will be categorised using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5. The number of patients who suffer a grade 3 or 4 toxicity at any time, and the maximum grade of toxicity for each adverse event term, will be described by trial arm
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)
Time Frame: 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 will be categorised using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5. The percentage of patients who suffer a grade 3 or 4 toxicity at any time, and the maximum grade of toxicity for each adverse event term, will be described by trial arm
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)
Time Frame: 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)
measured using European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC questionnaires): Quality of Life cancer 30 (QLQ-C30) (suitable for all cancer types) and Qualify of life questionnaire (QLQ-OV28 (ovarian cancer-specific)) in scale of 4 (1 is not very much and 4 very much)
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)
Time Frame: 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)
measured using European Quality of life questionnaire five dimensions (EQ-5D (descriptive profile of health state)) in scale of 5 (1 is no problem and 5 is extreme problem)
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
Time Frame: 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)
measured using Fear of progression questionnaire (FOP-Q SF) in scale of 1 to 5 where 1 is never and 5 is very often
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
Time Frame: 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.
measured at baseline, 3-weekly during treatment, 6-weekly during surveillance and 12-weekly during follow-up
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)
Time Frame: Additional treatment of patients who progress will be described by trial arm, this will include the time-to-next treatment (measured from randomisation).
of patients who progress will be described by trial arm including the time-to-next treatment (measured from randomisation)
Additional treatment of patients who progress will be described by trial arm, this will include the time-to-next treatment (measured from randomisation).
Further treatment (2/3)
Time Frame: Additional treatment of patients who progress will be described by trial arm, this will include the time treatment received (measured from randomisation)
of patients who progress will be described by trial arm including the time treatment received (measured from randomisation)
Additional treatment of patients who progress will be described by trial arm, this will include the time treatment received (measured from randomisation)
Further treatment (3/3)
Time Frame: Additional treatment of patients who progress will be described by trial arm, this will include the time response to this treatment (measured from randomisation)
of patients who progress will be described by trial arm including the time response to this treatment (measured from randomisation)
Additional treatment of patients who progress will be described by trial arm, this will include the time response to this treatment (measured from randomisation)
Overall survival
Time Frame: Measured from the date of randomisation to the date of death from any cause, censored at the date last seen (estimate 2 years but can be up to 4 years)
measured from the date of randomisation to the date of death from any cause. Patients who are event-free will be censored at the date last seen
Measured from the date of randomisation to the date of death from any cause, censored at the date last seen (estimate 2 years but can be up to 4 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

Barts & The London NHS Trust
Anticancer Fund, Belgium
JP Moulton Charitable Foundation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 24, 2023

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

November 1, 2027

Study Registration Dates

First Submitted

June 16, 2021

First Submitted That Met QC Criteria

October 12, 2021

First Posted (Actual)

October 15, 2021

Study Record Updates

Last Update Posted (Actual)

April 12, 2024

Last Update Submitted That Met QC Criteria

April 11, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 136618

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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