Phase III randomized clinical trial for stage III epithelial ovarian cancer randomizing between primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy: OVHIPEC-2

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Jan 2020 → ongoing

Decision date (initial)

2024-04-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Dutch Cancer Society (KWF)

External identifiers

EU CT number

2023-509049-11-00

EudraCT number

2018-003346-17

ClinicalTrials.gov

NCT03772028

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary objective of this study is to evaluate the effect of HIPEC on overall survival when added to primary cytoreductive surgery in patients with FIGO stage III ovarian cancer who are eligible for primary cytoreductive surgery resulting in no residual disease, or residual disease up to 2.5 mm.

Secondary objectives 3

1. To compare recurrence-free survival between both treatment arms
2. To compare time to first subsequent anticancer treatment after first recurrent disease (TFST)
3. To compare toxicity and morbidity between both treatment arms

Conditions and MedDRA coding

FIGO stage III ovarian cancer who are eligible for primary cytoreductive surgery resulting in non-residual disease, or residual disease up to 2.5 mm

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. signed and written informed consent
2. age ≥18
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 suspicious 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
5. adequate bone marrow function (hemoglobin level >5.5 mmol/L; leukocytes >3 x 109/L; platelets >100 x 109 /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.

Exclusion criteria 8

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 synchronal 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is overall survival, defined as the time from randomization to the date of death from any cause. For subjects that are alive, their survival time will be censored at the date of last contact (“last known alive date”). Overall survival will be censored for subjects at the date of randomization if they were randomized but had no follow-up.

Secondary endpoints 3

1. Recurrence-free survival is defined as the time between the date of randomization and the first date of documented disease progression or recurrence, as determined by the GCIG criteria (Appendix 1) , or death due to any cause, whichever occurs first (36). Disease recurrence or progression will be regularly evaluated via a standardized follow-up scheme and/or following clinical symptoms.
2. The time to first subsequent anticancer treatment after first recurrent disease (TFST)
3. The toxicity and morbidity will be reported until 30 days after the end of chemotherapy, using the Common Toxicity Criteria for Adverse Events (CTCAE v5.0) for all events, and using the Clavien-Dindo method for surgery-related events.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

W. van Driel

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Department of Gynaecology

Locations

7 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications