Heated intraperitoneal chemotherapy for the treatment of primary ovarian cancer
| ISRCTN | ISRCTN78284158 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78284158 |
| EudraCT/CTIS number | 2018-003346-17 |
| IRAS number | 1010654 |
| ClinicalTrials.gov number | NCT03772028 |
- Submission date
- 05/12/2024
- Registration date
- 10/04/2025
- Last edited
- 10/04/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
Background and study aims
This trial is for patients with FIGO stage III epithelial ovarian cancer who are eligible for primary cytoreductive surgery. Patients will receive primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy.
Hyperthermic intraperitoneal chemotherapy (HIPEC) involves administering a heated chemotherapy solution at a temperatures of 41-42°C into the peritoneal cavity [abdomen and pelvis] after cytoreductive surgery. Heated chemotherapy increases the penetration of chemotherapy administered into tissues in the abdominal and pelvic cavity.
A previous study (OVHIPEC-1) showed that combining hyperthermic intraperitoneal chemotherapy (HIPEC) with interval cytoreductive surgery (that is, surgery performed in patients initially treated with intravenous chemotherapy) significantly improves recurrence-free and overall survival for patients. A survival benefit of nearly one year was shown in patients who underwent HIPEC compared to those who did not have HIPEC. Patients in the OVHIPEC-1 study were ineligible for primary cytoreductive surgery due to extensive intra-abdominal disease and were instead initially treated with intravenous chemotherapy .
Who can participate?
Patients aged 18 years or older, with histologically proven FIGO stage III primary epithelial ovarian, fallopian tube, or extra-ovarian cancer, treated with primary complete cytoreduction, or primary cytoreduction with no more than 2.5 mm residual disease.
What does the study involve?
In the OVHIPEC-2 study, all patients will initially be treated with cytoreductive surgery with or without HIPEC. The study will evaluate whether patients treated with initial cytoreductive surgery and HIPEC have an increased overall survival compared to the overall survival in patients who are initially treated with surgery alone.
Follow-up visits will be scheduled every 3 months in the first two years and every six months during years 3-5.
What are the possible benefits and risks of participating?
Benefits:
Not provided at time of registration
Risks:
Potential for kidney toxicity - offset by use of sodium thiosulphate. Patients who receive HIPEC will have an additional 2-2.5 hours of general anaesthesia. Multiple studies indicate that patient safety is not compromised in those receiving HIPEC . If during the surgical procedure the patient is not well, or the surgical goal is not achieved [no visible disease, or any residual disease must be < 2.5mm in maximum diameter] then they will not be randomised in the study and will not receive HIPEC
Where is the study run from?
The Netherlands Cancer Institute
When is the study starting and how long is it expected to run for?
January 2020 to April 2026
Who is funding the study?
Dutch Cancer Foundation (Netherlands)
Who is the main contact?
Dr Desmond Barton, desmond.barton@rmh.nhs.uk
Dr Willemien van Driel, w.v.driel@nki.nl
ovhipec@nki.nl
Contact information
Public, Scientific
NKI-AVL/CGOA
Plesmanlaan 121
Amsterdam
1066 CX
Netherlands
| Phone | +31 (0)20 5124949 *2975 |
|---|---|
| w.v.driel@nki.nl |
Principal Investigator
Downs Road
Sutton
SM2 5PT
United Kingdom
| desmond.barton@rmh.nhs.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | Heated intraperitoneal chemotherapy (HIPEC) for the treatment of primary ovarian cancer |
| Study acronym | OVHIPEC-2 |
| Study hypothesis | Primary objective: To compare the overall survival rates in patients with primary ovarian cancer whose initial treatment was with surgery alone or surgery with heated intraperitoneal chemotherapy. Secondary objectives: 1. To look at recurrence-free survival rates in patients with primary ovarian cancer whose initial treatment was with surgery alone or surgery with heated intraperitoneal chemotherapy. 2. To look at the time to the first subsequent anticancer treatment after first recurrent disease in patients with ovarian cancer whose initial treatment was with surgery alone or surgery with heated intraperitoneal chemotherapy. |
| Ethics approval(s) |
Approved 28/01/2025, South Central - Berkshire Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 2071048143; berkshire.rec@hra.nhs.uk), ref: 24/SC/0412 |
| Condition | Stage III epithelial ovarian cancer |
| Intervention | There are two trial arms. 1. HIPEC – Intervention Arm •Primary cytoreductive surgery with HIPEC (Hyperthermic Intraperitoneal Chemotherapy) with cisplatin Cytoreductive Surgery is performed to remove all visible disease from the abdomen and pelvis. After 90 minutes the abdomen and pelvis are thoroughly irrigated and sodium thiosulphate is administered intravenously to protect the kidney function. 2. Conventional Surgery – Standard of Care •Primary cytoreductive surgery without HIPEC Cytoreductive Surgery is performed to remove all visible disease from the abdomen and pelvis. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Therapy |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Cisplatin |
| Primary outcome measure | 1. Overall survival is measured using patient records at baseline and at each follow-up visit 2. Survival time points for patients who are alive is measured using patient records at the date of last contact 3. Overall survival for patients with no follow-up is measured using patient records at the date of randomization |
| Secondary outcome measures | 1. Recurrence-free survival is measured using GCIG criteria in combination with clinical and/or radiological assessments at baseline and at each follow-up visit 2. Time to first subsequent anticancer treatment after first recurrent disease (TFST) is measured using patient records at the time of recurrence and at each follow-up visit 3. Toxicity and morbidity are measured using patient records and clinical assessments at baseline, during chemotherapy, and 30 days after the end of chemotherapy |
| Overall study start date | 01/01/2020 |
| Overall study end date | 01/04/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 538 |
| Participant inclusion criteria | 1. Signed and written informed consent 2. Age ≥18 years 3. Histological proven FIGO stage III primary epithelial ovarian, fallopian tube, or extra-ovarian cancer, treated with primary complete cytoreduction, or primary cytoreduction with no more than 2.5 mm residual disease a. in case of extra-abdominal enlarged lymph nodes, representative cytology/histology or FDG-PET scan must be negative; b. resectable, local bowel involvement, iatrogenic abdominal wall metastases or umbilical lesions are allowed; c. in case no histological proof is available before surgery, patients can be randomized during surgery based on histological proof on intraoperative frozen section material 4. Fit for major surgery, WHO performance status 0-2 Adequate bone marrow function (haemoglobin level >5.5 mmol/L; leukocytes >3 x 10^9/L; platelets >100 x 10^9 /L) 6. Adequate hepatic function (ALT, AST and bilirubin <2.5 times upper limit of normal) a. in case of Gilbert’s disease: unconjugated bilirubin <5 times upper limit of normal 7. Adequate renal function (creatinine clearance ≥ 60 ml/min or ml/min/1.73 m² using either MDRD, Cockcroft-Gault formula, or CKD-EPI) 8. Baseline health-outcome questionnaire should be completed before randomization 9. Able to understand the patient information and questionnaires. |
| Participant exclusion criteria | 1. History of previous malignancy treated with chemotherapy 2. History of previous malignancy within five years prior to inclusion, with the exception of carcinoma in situ, radically excised basal cell or squamous cell cancer of the skin or synchronous endometrial carcinoma FIGO IA G1/2 3. If complete primary cytoreduction is not feasible, for the following reasons: a. diffuse deep infiltration of the root of small bowel mesentery, or; b. diffuse carcinomatosis of the small bowel that requires resection that leads to short bowel syndrome (remaining bowel <1.5 meter), or; c. diffuse involvement/deep infiltration of stomach/duodenum, or; d. diffuse involvement/deep infiltration of head or middle part of pancreas, or; e. involvement of truncus coeliacus , hepatic arteries or left gastric artery, or; f. non-resectable enlarged (larger than 10 mm short axis) lymph nodes 4. In case of a known psychiatric disorder, substance abuse disorder, or high suspicion of a mental disorder that could interfere with cooperation or compliance with the requirements of the trial 5. When opting for fertility sparing surgery, or when breastfeeding 6. In case of a known history of Human Immunodeficiency Virus (HIV, or HIV 1/2 antibodies) 7. In case of known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative]) 8. Patients who received prior treatment for the current malignancy. |
| Recruitment start date | 01/01/2020 |
| Recruitment end date | 31/12/2025 |
Locations
Countries of recruitment
- Denmark
- England
- France
- Ireland
- Italy
- Netherlands
- Sweden
Study participating centre
Sutton
SM2 5PT
United Kingdom
Sponsor information
Hospital/treatment centre
Plesmanlaan 121
Amsterdam
1066 CX
Netherlands
| w.v.driel@nki.nl | |
| Website | https://www.nki.nl |
"ROR" |
https://ror.org/03xqtf034 |
Funders
Funder type
Charity
No information available
Results and Publications
| Intention to publish date | 01/04/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Submission to regulatory authorities Access to raw data and right to publish freely by all investigators in study or by Independent Steering Committee on behalf of all investigators As specified in the informed consent, it is stated that encoded data may be shared outside the EU, due to the international nature of the study. The patients explicitly consent to sharing of data for research purposes. |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Editorial Notes
05/12/2024: Trial's existence confirmed by NHS HRA.
