Gastric Cancer, Peritoneal Carcinomatosis
Conditions
Keywords
Gastric cancer, Peritoneal carcinomatosis, PIPAC, FOLFOX, Bidirectional
Brief summary
Peritoneum is among the most common sites of metastases in gastric cancer. Systemic chemotherapy is the current standard for peritoneal carcinomatosis (PC), although, the treatment results remain extremely poor. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a modern treatment modality for PC, that 1) optimize the drug distribution by applying an aerosol rather than a liquid solution; and 2) apply increased intraperitoneal hydrostatic pressure to increase drug penetration to the target. Despite some encouraging preliminary results for PIPAC efficacy, it is still an investigational treatment. Furthermore, only very limited data exist for bidirectional treatment, which includes a combination of systemic chemotherapy and PIPAC. Thus, this study will investigate the feasibility of PIPAC and systemic chemotherapy combination for gastric cancer patients with peritoneal metastases.
Detailed description
This open-label, single-arm feasibility study will be conducted at two major gastrointestinal cancer treatment centers in Lithuania and will include 37 participants. Gastric cancer patients diagnosed with a synchronous or metachronous peritoneal carcinomatosis based on a clinical, radiological, cytological, and histological examination will be considered for enrollment. Thirty-seven patients willing to participate and meeting the enrollment criteria will be scheduled for the experimental treatment. Three cycles of 1st line palliative systemic chemotherapy will be administered every 28 days and PIPAC with cisplatin 10,5 mg/m2 and doxorubicin 2,1 mg/m2 will be utilized 14 days after each of the systemic chemotherapy cycles. After the 3rd PIPAC procedure patients will be re-assessed and discussed at multidisciplinary team meetings. In case of downstaging patients will be considered for radical gastrectomy±cytoreductive surgery; others for further systemic therapy. All patients will be followed up for 24 months.
Interventions
DRUGCombined Doxorubicin and Cisplatin Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic FOLFOX chemotherapy
Each course of combined treatment will start with PIPAC (a pressurized aerosol containing cisplatin 10.5 mg/m2 and doxorubicin 2.1 mg/m2 diluted in NaCl 0.9% applied through the nebulizer inside the abdominal cavity during laparoscopy). Fourteen days afterward 2 cycles of systemic FOLFOX chemotherapy will be applied within 28 days. The interval between combined treatment courses will be 14 days.
Sponsors
Vilnius University Hospital Santaros Klinikos
National Cancer Institute (NCI)
Vilnius University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically verified gastric adenocarcinoma (HER2 negative) with peritoneal carcinomatosis; 2. Age≥18; 3. ECOG≤1; 4. Patient willing to participate; 5. Patient is the candidate for 1st line FOLFOX palliative systemic chemotherapy.
Exclusion criteria
1. Extra-abdominal metastases; 2. Siewert I type gastroesophageal junction cancer; 3. Mechanical bowel obstruction; 4. Allergy to study drugs; 5. History of previous intraperitoneal chemotherapy; 6. Pregnancy of refusal for birth-control at least 6 months post-study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective tumor response according to RECIST v 1.1 after second PIPAC | Day 7 after second PIPAC procedure (an average of 8 weeks after start of the study) | Objective tumor response according to RECIST v 1.1 in CT scan performed 1 week after second PIPAC procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor markers | Through study completion, an average of 28 months | Ca19-9, carcinoembryonic antigen (CEA), Ca72-4 plasma levels measured at different time points. |
| Quality of life by EORTC questionnaires | Through study completion, an average of 28 months | Quality of life by EORTC questionnaires measured at different time points. |
| Objective tumor response according to RECIST v 1.1 | Day 7 after third PIPAC procedure (an average of 15 weeks after start of the study) | Objective tumor response according to RECIST v 1.1 in CT scan performed 1 week after third PIPAC procedure |
| Compliance to treatment | Through study completion, an average of 28 months | Proportion of patients able to receive all anticipated treatment (3 PIPACs and 6 cycles of FOLFOX) |
| Overall survival | From treatment start to death, assessed up to 24 months | Time from start of the treatment to death |
| Peritoneal carcinomatosis index and histological regression according to peritoneal regression grading score (PRGS). | Through study completion, an average of 28 months | A pathologist blinded to clinical outcomes will evaluate histological tumor response using the Peritoneal Regression Grading Score (PRGS): 1-Complete regression without cancer cells; 2-higher response with prevalence of regressive phenomena and only a few residual cancer cells - PRGS; 3-minor response with prevalence of residual cancer cells and poor regressive phenomena; 4-no response to therapy without regressive phenomena. A patient will be considered a responder if any reduction in the PRGS during subsequent biopsies will be recorded. |
| Ascites volume | Through study completion, an average of 28 months | The volume of ascites recorded at every PIPAC procedure. |
| Progression-free survival | From treatment start to death, assessed up to 24 months | Time from start of the treatment to progression of the disease |
| Adverse events of chemotherapy drugs | Through study completion, an average of 28 months | The number of patients with toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0 during the study period |
| Postoperative complication assessed by Clavien-Dindo score | Through study completion, an average of 28 months | The number of patients with postoperative complications, defined and graded according to Clavien-Dindo classification |
Countries
Lithuania
Outcome results
None listed