Secondary Debulking Surgery +/- Hyperthermic Intraperitoneal Chemotherapy in Stage III Ovarian Cancer
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Hyperthermia; Fever
Study type: Interventional
Phase: Phase 3

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

Detailed description: 
      Rationale: Ovarian cancer is the second most common gynaecologic cancer in the Netherlands
      preceded by endometrial cancer. It is however the leading cause of death among women with
      gynaecologic malignancies with an annual mortality rate of 9 per 100.000. The majority of the
      patients are diagnosed with a high stage ovarian carcinoma due to the fact that symptoms
      occur at a late stage of the disease and screening methods for ovarian cancer are suboptimal.
      Optimal treatment consists of a combination of chemotherapy and debulking surgery. Despite
      the appearance of localized disease and the absence of obvious residual tumour following
      primary treatment, the majority of patients (80%) will have persistent disease or will
      develop recurrent disease. Additional strategies are warranted to reduce the recurrence rate
      and increase disease free survival and overall survival in this group of patients.

      The concept of administering intraperitoneal chemotherapy is based on the ideas on peritoneal
      dialysis. Intraperitoneal drug therapy is designed to maximize drug delivery to the tumour
      with generally acceptable systemic side effects associated with IV administration of the
      drug. This strategy is especially attractive for treatment of ovarian carcinoma, which
      remains largely restricted to the abdominal cavity for most of its natural history. So far 3
      randomised controlled trials have shown an overall and progression-free survival benefit when
      cisplatin is administered postoperatively by the IP route in patients with stage III,
      optimally resected disease. These studies however found that the majority of patients did not
      complete all planned 6 cycles due to catheter related problems. An alternative way of
      administering chemotherapy intra abdominally whilst bypassing the use of a catheter intra-
      abdominally is provided by perfusion of the abdomen during surgery under hyperthermic
      conditions. This study compares the interval debulking plus or minus the perfusion of the
      abdomen with chemotherapy under hyperthermic conditions during surgery (OVHIPEC).

      Objective: The primary objectives of this study are comparing the duration of recurrence free
      survival following completion of treatment between the 2 study arms.

      Secondary objectives of this study involve toxicity and morbidity, quality of life, tumour
      response following treatment and overall survival of the study arm compared to the standard
      arm.

      Study design: Phase III randomised trial Study population: Patients diagnosed with stage III
      ovarian carcinoma, peritoneal cell carcinoma or tuba carcinoma who are eligible for interval
      debulking surgery either following primary chemotherapy or following incomplete primary
      debulking and chemotherapy. Age between 18 - 76 yr old.

      Intervention: One group undergoes interval debulking with hyperthermic perfusion of the
      abdominal cavity with cisplatin 100 mg/m2 at the end of surgery. The other group is treated
      by interval debulking only.

      Main study parameters/endpoints: Recurrence free survival Nature and extent of the burden and
      risks associated with participation, benefit and group relatedness: Participants of the study
      will be asked to fill in quality of life questionnaires (12 times in 2 year). Blood samples
      will be taken following written informed consent before treatment, during surgery and during
      follow-up visits for marker studies and proteomics studies (10 times during 2 year). For
      patients participating in the pharmacokinetic studies (20) 2 tissue samples will be taken
      from the abdominal cavity during surgery and blood samples will be taken 6 times during and
      after surgery.

      During follow-up 3 monthly visits will be scheduled in the first 2 years and 6-monthly visits
      during year 3-5. During these follow-up visits routine physical exam including pelvic exam
      and vaginal ultrasound (optional) is performed. CT-scans will be performed in the first 2
      years before randomisation and 4 times at follow-up.

      Risks of participating in this trial are related to the abdominal perfusion of cisplatin.
      This can cause systemic effects such as: nephrotoxicity, bone marrow toxicity, neurotoxicity,
      and longer hospital stay. It can also increase the chance on bowel perforation of a bowel
      anastomoses resulting in a longer hospital stay and possibly surgical intervention. To
      prevent systemic side effects of intra-abdominally administered cisplatin, sodium
      thiosulphate is administered intravenously during surgery.
    

Intervention name(s): Secondary debulking; secondary debulking with intraperitoneal chemotherapy
Intervention type(s): Procedure; Procedure
Intervention description(s): Secondary debulking; secondary debulking with intraperitoneal chemotherapy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ovarian Cancer; stage III; hyperthermic intraperitoneal chemotherapy; debulking surgery; HIPEC