Abstract
BackgroundRecurrent, platin-resistant ovarian cancer (rPROC) has a poor survival. Even with the AURELIA trial, which is the best available treatment today, progression-free survival (PFS) is still only 6.7 months from the start of the second-line chemotherapy. Innovative, effective therapies are urgently needed. Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery system for administering drugs into the abdomen. PIPAC with cisplatin and doxorubicin (PIPAC C/D) may be safely used at an intraperitoneal dose of 10.5 mg/m2 and 2.1 mg/m2, respectively. Systemic toxicity of this therapy is low. In a phase II trial with 53 women, 62 % patients had an objective tumor response. Tumor regression on histology was observed in 76 % patients who underwent all three PIPACs. Randomized phase III studies are now required to evaluate the effect of PIPAC C/D compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy).MethodsThe present phase III study is a prospective, open, randomized, multicentric pivotal trial. A total of 244 patients will be randomly assigned (1:1) to the control (A) or to the experimental (B) group. Group A: Systemic palliative chemotherapy, physician’s best choice (monotherapy consisting of pegylated liposomal doxorubicin or topotecan or gemcitabine or paclitaxel weekly. Bevacizumab can be used in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin). Group B: Intraperitoneal chemotherapy, 3×PIPAC C/D, performed every 6 weeks. Combination with systemic therapy is not allowed. Treatment is continued until disease progression, death, or patient refusal. In case of progression, no recommendation for further therapy is given by protocol. Patients are allowed to receive PIPAC C/D or systemic chemotherapy after study termination. The primary endpoint is PFS (according to RECIST v1.1) or death from any cause. The co-primary endpoint is the health-related quality of life (HRQoL) measured as the global health status (GHS, QLQ-30 of EORTC). Secondary outcomes comprise overall survival, safety (CTCAE 5.0), and tumor response according to peritoneal regression grading score (PRGS).DiscussionWe expect PIPAC C/D to control peritoneal disease and preserve the QoL on this subset of patients.Trial registrationThe EudraCT number 2018-003664-31
Highlights
Rationale: context and hypothesisWith 295 000 new cases and 184 000 deaths worldwide in 2018 [1], ovarian cancer is a rare but lethal disease
The co-primary endpoint is the health-related quality of life (HRQoL) measured as the global health status (GHS, QLQ-30 of EORTC)
Secondary outcomes comprise overall survival, safety (CTCAE 5.0), and tumor response according to peritoneal regression grading score (PRGS)
Summary
With 295 000 new cases and 184 000 deaths worldwide in 2018 [1], ovarian cancer is a rare but lethal disease. Platinum-resistant recurrence represents 25 % of all recurrent cases and has a very poor prognosis with a progression-free survival (PFS) of 3.4 months, which may be extended to 6.7 months with the addition of bevacizumab as shown in the AURELIA trial [8]. There is an urgent need for innovative, better therapies for platinum-resistant, recurrent ovarian cancer. Pressurized Intraperitoneal Chemotherapy (PIPAC) is a new way of administration of intraperitoneal chemotherapy. This innovative approach to treat peritoneal metastases has been assessed in women with gynecologic malignancies [9]. Tempfer et al showed that PIPAC is feasible and has a safe local and systemic safety profile in women with peritoneal metastases from recurrent ovarian cancer. We expect PIPAC to control peritoneal disease and preserve the quality of life (QoL) on this subset of patients [8]
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