E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
stage III epithelial ovarian cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033163 |
E.1.2 | Term | Ovarian epithelial cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to prove the beneficial effect of complete or near-complete (residual disease ≤2.5 mm) primary cytoreductive surgery (CRS) in combination with HIPEC (treatment arm) resulting in improved outcome compared to primary cytoreductive surgery without HIPEC (standard arm) with acceptable morbidity, in patients with FIGO stage III epithelial ovarian cancer. |
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E.2.2 | Secondary objectives of the trial |
- To show the addition of HIPEC improves recurrence-free survival - To evaluate the toxicity and morbidity of both treatment arms - To evaluate the quality of life of the treatment arm compared to the standard arm - To assess genetic profiles predictive of tumor response in patients with stage III ovarian cancer undergoing primary CRS with or without HIPEC - To assess an economic- and cost evaluation of the procedure |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 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 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.
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E.4 | Principal 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 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 1 year of follow up |
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E.5.2 | Secondary end point(s) |
- Recurrence-free survival (RFS) - The toxicity and morbidity of both treatment arms - The quality of life of both treatment arms - Economic- and cost evaluation of the procedure |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- RFS is defined as time between the date of randomization and the first date of documented disease progression or recurrence, as determined by the GCIG criteria (Appendix 1) in combination with clinical and/or radiological assessments (36), or death due to any cause, whichever occurs first. - QoL and cost effectiveness: after 6 years (after one year of follow up) - Safety: after 30 days after last treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
HIPEC treatment during surgery or no HIPEC treatment |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Denmark |
France |
Ireland |
Italy |
Netherlands |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |