Secondary Debulking Surgery +/- Hyperthermic Intraperitoneal Chemotherapy in Stage III Ovarian Cancer

This study evaluates the efficacy and safety of the addition of hyperthermic intraperitoneal chemotherapy to secondary debulking surgery in stage III ovarian cancer.

Sex

Female

Minimum age

18 Years

Maximum age

76 Years

Inclusion Criteria:

* Age between 18 and 76 years
* Histological or cytological proven primary epithelial ovarian carcinoma or peritoneal cancer (PPSC) or fallopian tube carcinoma FIGO stage III, including serous papillary adenocarcinoma, mucinous adenocarcinoma and endometrioid adenocarcinoma.
* In case of pleural effusion cytology should be negative for tumour cells
* In case diagnosis is made based on cytology only (i.e. patients treated by primary chemotherapy) additional criteria apply:

  * Normal mammogram (\< 6 weeks before first registration) and
  * Presence of pelvic mass and
  * CA 125 \> 200 kU/l and
  * Serum CA125/CEA ratio \> 25. If the serum CA125/CEA ratio is \< 25, a barium enema or colonoscopy and gastroscopy or radiological examination of the stomach should be negative for the presence of a primary tumour of the digeste tract (\< 6 weeks before registration) and
  * Omental cake or other metastases larger than 2 cm in the upper abdomen and/or regional lymph node metastasis irrespective of size (CT/MRI or ultrasound or laparoscopy)
* Patients eligible for interval debulking for the following 2 reasons:

  * Primary debulking surgery not feasible due to tumour extension or general condition (patients treated by primary chemotherapy) or
  * Incomplete primary debulking with residual disease \> 1 cm
* In case of primary chemotherapy:

  * Chemotherapy consists of 3 courses of carboplatin or cisplatin combined with taxol
  * Following 2 cycles of chemotherapy at least a 30% decrease in the sum of largest diameter (LD) of target lesions taking as reference the baseline sum LD (RECIST criteria, see appendix 1)
* In case of an incomplete primary debulking as indicated under 5 followed by chemotherapy:

  * Chemotherapy consists of 3 courses of carboplatin or cisplatin combined with taxol
* General criteria:

  * Fit for major surgery, ASA 1 or ASA 2
  * WHO performance status 0-2
  * Written informed consent
  * Laboratory values: serum creatinine \< 140 µmol/L; creatinine clearance \> 60 ml/min (Cockroft formula); white blood cell count \> 3.5 x 109/l; platelets \> 100 x 109 /l
* For quality of life studies:

  * Baseline questionnaires should be filled in before randomization

Exclusion Criteria:

* History of breast cancer or previous malignancies within 5 years prior to inclusion, with the exception of radically excised basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

• DERIVEDAronson SL, Walker C, Thijssen B, van de Vijver KK, Horlings HM, Sanders J, Alkemade M, Koole SN, Lopez-Yurda M, Lok CAR; OVHIPEC-1 Study Group; Rottenberg S, van Rheenen J, Sonke GS, van Driel WJ, Kester LA, Hahn K. Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1). Br J Cancer. 2024 Aug;131(3):565-576. doi: 10.1038/s41416-024-02731-6. Epub 2024 Jun 12. PMID 38866963
• DERIVEDAronson SL, Lopez-Yurda M, Koole SN, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, de Hingh IHJT, van Gent MDJM, Arts HJG, van Ham MAPC, van Dam PA, Vuylsteke P, Aalbers AGJ, Verwaal VJ, Van de Vijver KK, Aaronson NK, Sonke GS, van Driel WJ. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial. Lancet Oncol. 2023 Oct;24(10):1109-1118. doi: 10.1016/S1470-2045(23)00396-0. Epub 2023 Sep 11. PMID 37708912
• DERIVEDUbachs J, Koole SN, Lahaye M, Fabris C, Bruijs L, Schagen van Leeuwen J, Schreuder HWR, Hermans RH, de Hingh IH, van der Velden J, Arts HJ, van Ham M, van Dam P, Vuylsteke P, Bastings J, Kruitwagen RFPM, Lambrechts S, Olde Damink SWM, Rensen SS, Van Gorp T, Sonke GS, van Driel WJ. No influence of sarcopenia on survival of ovarian cancer patients in a prospective validation study. Gynecol Oncol. 2020 Dec;159(3):706-711. doi: 10.1016/j.ygyno.2020.09.042. Epub 2020 Oct 2. PMID 33019981
• DERIVEDKoole SN, van Lieshout C, van Driel WJ, van Schagen E, Sikorska K, Kieffer JM, Schagen van Leeuwen JH, Schreuder HWR, Hermans RH, de Hingh IH, van der Velden J, Arts HJ, Massuger LFAG, Aalbers AG, Verwaal VJ, Van de Vijver KK, Aaronson NK, van Tinteren H, Sonke GS, van Harten WH, Retel VP. Cost Effectiveness of Interval Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy in Stage III Ovarian Cancer on the Basis of a Randomized Phase III Trial. J Clin Oncol. 2019 Aug 10;37(23):2041-2050. doi: 10.1200/JCO.19.00594. Epub 2019 Jun 28. PMID 31251694
• DERIVEDKoole SN, Kieffer JM, K Sikorska, Schagen van Leeuwen JH, Schreuder HWR, Hermans RH, de Hingh IH, van der Velden J, Arts HJ, van Ham MAPC, Aalbers AG, Verwaal VJ, Van de Vijver KK, Sonke GS, van Driel WJ, Aaronson NK. Health-related quality of life after interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage III ovarian cancer. Eur J Surg Oncol. 2021 Jan;47(1):101-107. doi: 10.1016/j.ejso.2019.05.006. Epub 2019 May 13.