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

NCT ID: NCT05080556

Last Updated: 2024-04-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-24
• Study Completion Date: 2027-11-01

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.

Conditions

Ovarian Cancer; Relapsed Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer; Endometrioid Carcinoma; High Grade Serous Carcinoma; Ovary Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 (control) - standard dosing carboplatin

Arm 1 (Standard Dosing): Carboplatin AUC5 based on nuclear medicine renal clearance.

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

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.

Arm 2 (experimental) - adaptive therapy carboplatin according to CA125

Arm 2 (Adaptive Therapy): Carboplatin dose will be calculated according to the CA125 value.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Anticancer Fund, Belgium

OTHER

Sponsor Role: collaborator

JP Moulton Charitable Foundation

OTHER

Sponsor Role: collaborator

Barts & The London NHS Trust

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University College London Hospitals

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

ACTOv Trial Coordinator

Role: CONTACT

ctc.actov@ucl.ac.uk

02076794466

Facility Contacts

Michelle Lockley

Role: primary

michellelockley@nhs.net

References

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 relapsed platinum-sensitive high-grade serous or high-grade endometrioid ovarian cancer. BMJ Open. 2024 Dec 22;14(12):e091262. doi: 10.1136/bmjopen-2024-091262.

Reference Type: DERIVED

PMID: 39806715 (View on PubMed)

Other Identifiers

136618

Identifier Type: -

Identifier Source: org_study_id