Intraperitoneal Aerosol Chemotherapy in Gastric Cancer

Feasibility, Efficacy and Safety of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) With Cisplatin and Doxorubicin in Patients With Gastric Cancer and Peritoneal Carcinomatosis: an Open-label, Single-arm, Phase II Clinical Trial

A prospective series of patients with recurrent gastric cancer will be treated with three cycles of chemotherapy (doxorubicin and cisplatin) instilled into the abdominal cavity in the form of an aerosol under pressure via laparoscopy. The efficacy of this treatment will be assessed by computed tomography, tumor marker studies, and survival. Also, the safety of the procedure will be assessed.

Objectives: To evaluate the safety and efficacy in terms of the clinical benefit rate (CBR) of PIPAC in peritoneal carcinomatosis (PC) from gastric cancer (GC) Study design: Single center, open label, non-randomized, single-arm, repeated single dose study to explore the efficacy, safety, and CBR of doxorubicin and cisplatin when given as a pressurized intraperitoneal aerosol chemotherapy (PIPAC) to patients with advanced gastric cancer and peritoneal carcinomatosis.

Target subject population:Patients with GC and PC with disease progression after at least one line of previous i.v. chemotherapy.

Investigational product, dosage and mode of administration Doxorubicin 1.5 mg/m2 body surface in 50 ml NaCl 0,9% and Cisplatin 7.5 mg/m2 in 50 ml NaCl 0,9% q 4-6 weeks, applied intraperitoneally as PIPAC.

Duration of treatment: 3 single doses in 6 weeks intervals, duration of treatment is 18 weeks

Outcome variables:

1.1 Primary outcome variable • Clinical Benefit Rate (CBR) according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) after 3 cycles of PIPAC with cisplatin and doxorubicin.

1.2 Secondary outcome variables

• The observed survival (OS)
• The median time to progression (TTP) according to RECIST criteria after three cycles of PIPAC with cisplatin and doxorubicin
• The Peritoneal Carcinomatosis Index (PCI) before and after therapy
• The degree of histological regression assessed by pathological review
• Apoptosis as assessed by immunohistochemical analysis
• The difference in ascites volume before and after the first, second, and third PIPAC application 1.3 Patient reported outcomes (PROs)
• European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30, German version ) 1.4 Safety
• Safety and tolerability will be assessed by collection of adverse events, according to the Common Terminology Criteria for Adverse Events (CTCAE) including physical examination results, laboratory assessments (chemistry and hematology).

1.5 Biological monitoring

• Basic research investigating expression of genes associated with drug resistance.

Inclusion Criteria:

• age above 18 years
• written, informed consent
• presence of peritoneal carcinomatosis

Exclusion Criteria:

• language barrier
• parenchymal metastases
• unability to undergo laparoscopy