Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12621000269831
Ethics application status
Approved
Date submitted
7/12/2020
Date registered
11/03/2021
Date last updated
21/04/2025
Date data sharing statement initially provided
11/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Hyperthermic and Normothermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III epithelial OVArian, fallopian tube and primary peritoneal cancer.
Scientific title
The safety of hyperthermic and normothermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III epithelial ovarian, fallopian tube and primary peritoneal cancer (HYNOVA).
Secondary ID [1] 302946 0
CTC 0302
Secondary ID [2] 303144 0
ANZGOG 1901 /2020
Universal Trial Number (UTN)
Trial acronym
HyNOVA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian cancer 319979 0
Fallopian tube cancer 320844 0
Primary peritoneal cancer 320845 0
Condition category
Condition code
Cancer 317910 317910 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the experimental arm of normothermic intraperitoneal chemotherapy (NIPEC) will receive 100 mg/m² of cisplatin, heated to 37°C (normal body temperature), through a catheter into the abdominal cavity for 90 minutes during surgery
Intervention code [1] 319238 0
Treatment: Drugs
Comparator / control treatment
Participants in the comparator arm of Hyperthermic intraperitoneal chemotherapy (HIPEC) will receive 100 mg/m² of cisplatin, heated to 42°C, through a catheter into the abdominal cavity for 90 minutes during surgery.
Control group
Active

Outcomes
Primary outcome [1] 325924 0
Proportion of participants experiencing a grade 3-5 adverse event according to the Clavien-Dindo classification for surgical adverse events within 30 days after surgery.
Timepoint [1] 325924 0
Within 30 days post-surgery
Secondary outcome [1] 389527 0
The type and frequency of adverse events as measured by the NCI Common terminology criteria for adverse events (NCI-CTCAE version 5.0) within 90 days after surgery.
Timepoint [1] 389527 0
Within 90 days post-surgery.
Secondary outcome [2] 389528 0
Surgical morbidity in both groups by collecting data on length of intensive care unit (ICU) stay; readmission to ICU; duration of vasopressor use; intra-operative and post-operative blood transfusion; length of hospital stay; return to theatre; readmission to hospital; bowel function which includes time to first bowel motion, ileus requiring reinsertion of NGT, duration of total parenteral nutrition (TPN); use of a bowel stoma.
Timepoint [2] 389528 0
Within 90 days post-surgery
Secondary outcome [3] 389530 0
Resource utilisation. Hospitalisation information will be collected for all patients. Major components include days in intensive care units and days in hospital, returns to operating theatre, emergency room visits, and the number of days of total parenteral nutrition (TPN).
Timepoint [3] 389530 0
Duration of the trial
Secondary outcome [4] 389531 0
Feasibility of NIPEC which is defined as the proportion of participants that correctly received their randomised treatment and the proportion of participants that received all 6 cycles of chemotherapy. The total number of chemotherapy cycles received and dose reductions or change in chemotherapy will be collected.
Timepoint [4] 389531 0
After patients receive their randomised treatment and the proportion of patients that received all 6 cycles of chemotherapy.
Secondary outcome [5] 389532 0
Progression free survival which is defined as the time from randomisation until the date of first evidence of progression of disease as determined by the RECIST v1.1 criteria as assessed by the investigator, or death due to any cause, whichever comes first. Progression free survival according to CA125 measurements as per GCIG criteria for progression will also be assessed.
Timepoint [5] 389532 0
From randomisation until the date of first evidence of progression of disease.
Secondary outcome [6] 389533 0
Overall survival
Timepoint [6] 389533 0
From the date of randomisation to date of death from any cause.
Secondary outcome [7] 446594 0
Frequency of adverse events of interest within 90 days after surgery. These include blood and lymphatic system disorders; gastrointestinal disorders; infections and infestations; injury, poisoning, and procedural complications; renal and urinary disorders; respiratory, thoracic, and mediastinal disorders; cardiac disorders; vascular disorders.
Timepoint [7] 446594 0
Within 90 days after surgery.
Secondary outcome [8] 446595 0
Describe health-related quality of life using EORTC QLQ-C30 questionnaire
Timepoint [8] 446595 0
At 24 months post randomisation
Secondary outcome [9] 446596 0
Assess other patient-reported outcomes using the EORTC QLQ-C30 questionnaire as exploratory endpoints
Timepoint [9] 446596 0
At 24 months post randomisation
Secondary outcome [10] 446597 0
Assess other patient-reported outcomes using the QLQ-OV28 questionnaire as exploratory endpoints
Timepoint [10] 446597 0
At 24 months post-randomisation
Secondary outcome [11] 446598 0
Assess other patient-reported outcomes using the EORTC IL-114 questionnaire as exploratory endpoints
Timepoint [11] 446598 0
At 24 months post randomisation
Secondary outcome [12] 446599 0
Assess other patient-reported outcomes using the MOST-T24 questionnaire as exploratory endpoints
Timepoint [12] 446599 0
At 24 months post randomisation
Secondary outcome [13] 446600 0
Assess other patient-reported outcomes using the EuroQoL 5D (EQ-5D-5L) questionnaire as exploratory endpoints
Timepoint [13] 446600 0
At 24 months post randomisation

Eligibility
Key inclusion criteria
1. Age 18 -75 years
2. Participants diagnosed with primary FIGO stage III epithelial ovarian, fallopian tube or peritoneal cancer with disease that is limited to the abdominal cavity. This includes retroperitoneal lymph nodes involement, superficial/subcapsular liver lesions, and selected stage IV disease such as splenic disease, abdominal wall disease and full thickness bowel wall involvement if this can be resected with clear margins.
3. Histopathology must be high grade serous, endometroid (grade 2 and 3), clear cell adenocarcinoma or mixed high grade histologies.
4. Have 3-4 cycles of pre-operative platinum-based chemotherapy
5. No progression of disease on radiological imaging and/or Ca125 during neoadjuvant chemotherapy
6. ECOG performance status 0 or 1
7. Fit for surgery as determined by study surgical team
8. Surgery should be performed at least 21 days after cycle 3 or 4 day 1 (C3D22 or C4D22) but before day 42 (C3D42 or C4D42).
9. Adequate bone marrow function.
10. Adequate liver function
11. Adequate renal function as defined by creatinine clearance >50 ml/min as per Cockcroft-Gault formula.
12. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
13. Signed, written informed consent.
Minimum age
18 Years
Maximum age
75 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants with extra-abdominal disease.
2. Participants with intrahepatic or other visceral metastasis detected on radiological imaging which is not surgically resectable at diagnosis and/or after pre-operative chemotherapy treatment.
3. Any contraindications to receiving intraperitoneal cisplatin chemotherapy as per the treating medical oncologist such as drug allergy.
4. Had received bevacizumab in combination with neo-adjuvant chemotherapy treatment within 6 weeks of CRS.
5. Serious medical or psychiatric conditions that may prevent compliance with the protocol or that may compromise assessment of key outcomes
6. History of another malignancy within 5 years prior to registration. Participants with curatively treated cervical carcinoma in situ or non-melanomatous carcinoma of the skin, or participants who have been free of other malignancies for greater than or equal to 5 years prior to registration are eligible for this study
7. Concurrent illness, including active intra-abdominal sepsis that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety as determined by the study surgical team.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified dynamic allocation, randomly alternating between minimisation and complete randomisation and stratified according to hospital centre, age (=70 years vs > 70 years), histological type (serous vs non-serous vs undetermined), and peritoneal cancer index score at the time of surgery (= 15 vs > 15)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/02/2022
Actual
24/03/2022
Date of last participant enrolment
Anticipated
Actual
13/09/2024
Date of last data collection
Anticipated
Actual
31/12/2024
Sample size
Target
80
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 23499 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [2] 23500 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 23501 0
Mater Adult Hospital - South Brisbane
Recruitment postcode(s) [1] 38907 0
2050 - Camperdown
Recruitment postcode(s) [2] 38908 0
3000 - Melbourne
Recruitment postcode(s) [3] 38909 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 307368 0
Government body
Name [1] 307368 0
Australian Government - Medical Research Future Fund (MRFF)
Country [1] 307368 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
University of Sydney, Camperdown, NSW 2006
Country
Australia
Secondary sponsor category [1] 308022 0
None
Name [1] 308022 0
Address [1] 308022 0
Country [1] 308022 0
Other collaborator category [1] 281564 0
Other Collaborative groups
Name [1] 281564 0
Australia New Zealand Gynaecological Oncology Group (ANZGOG)
Address [1] 281564 0
Level 6, Chris O’Brien Lifehouse 119-143 Missenden Road, Camperdown, NSW 2050
Country [1] 281564 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307456 0
Sydney Local Health District (SLHD) - RPA Zone Research Ethics and Governance
Ethics committee address [1] 307456 0
Ethics committee country [1] 307456 0
Australia
Date submitted for ethics approval [1] 307456 0
24/11/2020
Approval date [1] 307456 0
19/03/2021
Ethics approval number [1] 307456 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107294 0
A/Prof Rhonda Farrell
Address 107294 0
NHMRC Clinical Trials Centre Level 6, Chris O'Brien Lifehouse 119-143 Missenden Road, Camperdown NSW 2050
Country 107294 0
Australia
Phone 107294 0
+61 2 8036 5262
Fax 107294 0
Email 107294 0
[email protected]
Contact person for public queries
Name 107295 0
HYNOVA Trial Operations Coordinator
Address 107295 0
NHMRC Clinical Trials Centre Level 6, Chris O'Brien Lifehouse 119-143 Missenden Road, Camperdown NSW 2050
Country 107295 0
Australia
Phone 107295 0
+61 2 9562 5000
Fax 107295 0
Email 107295 0
[email protected]
Contact person for scientific queries
Name 107296 0
HYNOVA Trial Operations Coordinator
Address 107296 0
NHMRC Clinical Trials Centre Level 6, Chris O'Brien Lifehouse 119-143 Missenden Road, Camperdown NSW 2050
Country 107296 0
Australia
Phone 107296 0
+61 2 9562 5000
Fax 107296 0
Email 107296 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: Currently no plan and participant informed consent will be required.



What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseClinical trial protocol for HyNOVA: Hyperthermic and normothermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage iii epithelial ovarian, fallopian tube and primary peritoneal cancer (ANZGOG1901/2020).2022https://dx.doi.org/10.3802/JGO.2022.33.E1
N.B. These documents automatically identified may not have been verified by the study sponsor.