Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Rare Diseases

Neoplasm Metastasis

Stomach Neoplasms

Neoplastic Processes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Paclitaxel

Leucovorin

Fluorouracil

Albumin-Bound Paclitaxel

Oxaliplatin

PIPAC (Paclitaxel) + Systemic mFOLFOX6(5-FU, Oxaliplatin, Leucovorin)

Aerosolization of chemotherapic agent for intraperitoneal chemotherapy

Pressurized Intraperitoneal Aerosol Chemotherapy

So Hyun Kang

This is a phase I trial investigating the safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) using paclitaxel combined with intravenous FOLFOX therapy for gastric cancer patients with peritoneal metastasis.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Using Paclitaxel in Gastric Cancer Patients With Peritoneal Metastasis

Safety of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Using Paclitaxel in Gastric Cancer Patients With Peritoneal Metastasis

Recommended dose of paclitaxel for a phase II trial

Hospicare Co., Ltd.

Seoul National University Bundang Hospital

Professor

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Pancreatic Neoplasms

Pleural Effusion

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ascites

Pleural Diseases

Mesothelioma

Mesothelioma, Malignant

Peritoneal Neoplasms

Pseudomyxoma Peritonei

Gallbladder Neoplasms

Appendiceal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Endocrine Gland Neoplasms

Endocrine System Diseases

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Respiratory Tract Diseases

Pancreatic Diseases

Biliary Tract Neoplasms

Biliary Tract Diseases

Gallbladder Diseases

Adenocarcinoma

Adenocarcinoma, Mucinous

Carcinoma

Neoplasms, Cystic, Mucinous, and Serous

Cecal Neoplasms

Cecal Diseases

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Gallbladder Cancer

Malignant Mesothelioma

Pharmaceutical Solutions

Gemcitabine

Doxorubicin

Liposomal doxorubicin

Cisplatin

Mitomycins

Mitomycin

A chemotherapeutic solution is aerosolized into the expanded abdominal cavity during laparoscopy, under pressure. This allows a relatively homogeneous repartition of the drug and an effective tissue penetration.

PIPAC

Sabine Rhode

Laura Lay, MD

Craig Lynch, MD

Tarkan Jäger, MD

Woulter Willaert, MD

Martin Graversen, MD

Catherine Arvieux, MD

Clarisse Eveno

Olivier Glehen, MD

Olivia Sgarbura, MD

Verena Schlaich

Marco Vaira, MD

Maciej Nowacki, MD

Vladimir Khomyakov, MD

Janelle Phua

Juan Torrent, MD

Martin Huebner, MD

Philipp Horvath, MD

Multicentric, international, web-based prospective documentation of the indications and results of Pressurized Aerosol Chemotherapy (so-called PIPAC or PITAC) for treating malignant pleural and peritoneal diseases. Indication is decided by the treating physician. There are no predefined inclusion or exclusion criteria.

All data entered into the registry documenting the patient cohort characteristics (disease, demography, therapy) are analyzed using descriptive statistics. Survival data are analyzed with Kaplan-Meier statistics. Multivariate Cox Proportional Hazard Models are used to identify potential prognostic and predictive factors. In particular, a risk- adjusted comparison of the outcome criteria with a propensity score is planned.

The data are stored in a SQL-based online database. Patient data are pseudoanonymized. The registry has received approval of the data protection officer of the State of Northrhine-Westphalia.

The study steering committee is blinded towards the identity of the participating institutions. Each participating institution receives an annual report with own data vs. benchmark. Scientific analysis can be proposed by the steering committee, by a participating institution or by other scientists, subjected to the approval of the independent scientific advisory board.

An export function has been built in to allow data exchange with the HIPEC Registry of the German Society for General and GI surgery (http://www.dgav.de/studoq/studoqhipec.html).

International Registry of Patients Treated With Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

Multicenter, International Online Documentation of Indications and Results of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC Und PITAC) for Treating Malignant Peritoneal and Pleural Diseases

Requests can be addressed to the Scientific Advisory Board, AnInstitut für Qualitässicherung in der operativen Medizin gGmbH, Leipziger Str. 44, 39120 MAGDEBURG, Germany

according to RECIST criteria (CR + PR + SD)

according to the Peritoneal Regression Grading Score (PRGS)

Ruhr University of Bochum

Coordinator

Abdominal Neoplasms

Peritoneal Diseases

Esophageal Cancer

Tubulin Modulators

Antimitotic Agents

3 patients will be allocated to PIPAC arm at Paclitaxel 15mg/m2. If there is 1 dose limiting toxicity (DLT), an additional 3 patients will be allocated to PIPAC arm at 15mg/m2. If there is 2 - 3 DLT, study had exceeded its Maximum Tolerable Dose (MTD) and we will proceed to stop recruitment.

Should there be no DLT, recruitment at PIPAC 30mg/m2 and ePIPAC 15mg/m2 will occurs concurrently in an alternating fashion. PIPAC/ePIPAC dose escalation will continue until a MTD has been reached. Should there be no DLT at PIPAC 30mg/m2 and ePIPAC 15mg/m2, recruitment at PIPAC 45mg/m2 and ePIPAC 30mg/m2 will occurs concurrently in an alternating fashion. Finally, should there be no DLT, recruitment at ePIPAC 45mg/m2 will occurs.

Should there be no DLT under PIPAC arm at Paclitaxel 15mg/m2, recruitment at ePIPAC 15mg/m2 and PIPAC 30mg/m2 will occurs concurrently in an alternating fashion. PIPAC/ePIPAC dose escalation will continue until a MTD has been reached. Should there be no DLT at PIPAC 30mg/m2 and ePIPAC 15mg/m2, recruitment at PIPAC 45mg/m2 and ePIPAC 30mg/m2 will occurs concurrently in an alternating fashion. Finally, should there be no DLT, recruitment at ePIPAC 45mg/m2 will occurs.

This is a prospective, two armed phase I trial in a 3 + 3 dose escalation evaluating the safety and tolerability of PIPAC/ePIPAC using paclitaxel in patients with peritoneal carcinomatosis.

Bok Yan Jimmy So, MBChB

Peritoneal carcinomatosis (PC) is a miserable disease with poor treatment outcome. Intraperitoneal administration of anticancer drugs enables an extremely high concentration of drugs to directly contact the target cancer lesions in the peritoneal cavity. However, its effectiveness is limited by the intraperitoneal distribution and penetration of the drug. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative intraperitoneal chemotherapy concept that enhances efficacy by taking advantage of the physical properties of gas and pressure. Electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (ePIPAC) may further enhance these benefits.

This research study serves to determine the safety profile and tolerability of PIPAC/ePIPAC with paclitaxel. It will determine the maximal tolerated dose (MTD) and evaluate the safety and tolerability, and pharmacokinetics of PIPAC/ePIPAC paclitaxel in pre-treated patients with peritoneal carcinomatosis (PC). It may offer a novel and effective option of treatment for patients with PC, who, at present have limited options involving the use of systemic chemotherapy and who suffer from poor life expectancy and poor quality of life.

In patients with histologically proven unresectable or recurrent gastric cancer limited to the peritoneum, the combination of intraperitoneal (IP) paclitaxel with systemic chemotherapy reported a one-year survival rate of 78%. However, the effectiveness of IP chemotherapy may be limited by its distribution, tissue penetration and associated catheter-related complications.

Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery technique for PC taking advantage of physical laws (gaseous nature, hydrostatic pressure) with superior pharmacological properties (homogeneous distribution, deeper tissue penetration). It is applied through laparoscopy and is minimally invasive. Adding electrostatic loading (ePIPAC) as an adjunct would further improve the pharmacological properties of PIPAC since it should induce precipitation of the aerosolized drug, increasing the ratio between the dose applied and the dose in the target tissue.

Systemic toxicity is significantly reduced due to the peritoneum/blood barrier and the low dose applied (about 20% of the usual systemic dose). A systematic review highlighted that PIPAC combines the benefits of a minimally invasive approach with pharmacokinetic advantages of intraperitoneal administration and pressurized vaporization. It concluded that PIPAC is feasible, safe, and warrants further prospective studies. PIPAC may be combined with systemic palliative chemotherapy with minimal additional organ toxicity. This method of treatment avoids the morbidity and mortality of HIPEC. PIPAC has been shown in pre-clinical studies to be potentially more efficacious than catheter-based IP-chemotherapy due to better drug distribution and penetration. In clinical use, PIPAC can be repeated at intervals of 6 weeks to 3 months. This allows repeated objective assessment of therapy effect over time.

To date, PIPAC has only been utilized to administer Oxaliplatin or a combination of Doxorubicin/Cisplatin. Paclitaxel is an approved drug for systemic chemotherapy for several cancers, and also has well-documented intraperitoneal use for ovarian cancer and gastric cancer. It is a hydrophobic, high molecular weight compound resulting in low absorption through the lymphatic system after IP administration with a much higher peritoneal to plasma peak concentration and AUC ratios (\>1000 versus 25 and \>1000 versus 16 respectively). As such, IP Paclitaxel may be potentially more efficacious with less systemic toxicity than IP Oxaliplatin. However, no clinical data exists in the published literature for PIPAC/ePIPAC paclitaxel.

This proposed prospective study is the first clinical study of PIPAC/ePIPAC with Paclitaxel. It will determine the maximal tolerated dose (MTD) and evaluate the safety and tolerability, and pharmacokinetics of PIPAC/ePIPAC paclitaxel in pre-treated patients with PC. Peritoneal biopsies will be collected prior to and after PIPAC/ePIPAC to assess tissue drug concentration and depth of drug penetration. Collection of biospecimens including peritoneal tissue, peritoneal fluid and blood will be used for correlative studies including paclitaxel resistance analysis and development of cancer modelling platforms. For the individual patient, repeated biopsies and molecular profiling may also facilitate individualized therapy. For medical research, PIPAC/ePIPAC may deliver measurable progress in 3-5 years because the assessment interval is short (6 weeks) in this disease with rapid progression (6-12 months to death).

This study will determine the safety dose range of PIPAC/ePIPAC paclitaxel. This will allow us to design a phase II trial to evaluate clinical efficacy. On a larger scale, the success of this PIPAC/ePIPAC trial would add a valuable treatment option to our arsenal in the treatment of PC.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) and Electrostatic PIPAC (ePIPAC) With Paclitaxel In Patients With Peritoneal Carcinomatosis

Phase 1 Study of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) and Electrostatic PIPAC (ePIPAC) With Paclitaxel for Peritoneal Carcinomatosis - PIPAC2 Study

Dose limiting toxicities are monitored to evaluate the tolerability of PIPAC /ePIPAC

Adverse events are monitored to evaluate the safety profile of PIPAC/ePIPAC

Peritoneal Cancer Index (PCI) is used to measure Clinical response of PIPAC/ePIPAC with Paclitaxel

Peritoneal Regression Grade Scoring (PRGS) System is used to measure Pathological response of PIPAC/ePIPAC

National University Hospital, Singapore

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Using Paclitaxel in Gastric Cancer Patients With Peritoneal Metastasis	NCT04913662	Stomach Neoplas... Peritoneal Meta...	Pressurized Int...	18 Years - 80 Years	Seoul National University Bundang Hospital
International Registry of Patients Treated With Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)	NCT03210298	Peritoneum Canc... Peritoneum Neop... Pleural Cancer Pleural Effusio... Pleural Mesothe... Ovarian Cancer Gastric Cancer Appendix Cancer Pseudomyxoma Pe... Colorectal Canc... Pancreas Cancer Gallbladder Can... Ascites CUP Chemotherapeuti...	PIPAC	10 Years -	University of Magdeburg
International Registry of Patients Treated With Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)	NCT03210298	Peritoneum Canc... Peritoneum Neop... Pleural Cancer Pleural Effusio... Pleural Mesothe... Ovarian Cancer Gastric Cancer Appendix Cancer Pseudomyxoma Pe... Colorectal Canc... Pancreas Cancer Gallbladder Can... Ascites CUP Chemotherapeuti...	PIPAC	10 Years -	University of Magdeburg
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) and Electrostatic PIPAC (ePIPAC) With Paclitaxel In Patients With Peritoneal Carcinomatosis	NCT05395910	Peritoneal Carc...	Paclitaxel	21 Years - 99 Years	National University Hospital, Singapore
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Using Paclitaxel in Gastric Cancer Patients With Peritoneal Metastasis	NCT04913662	Stomach Neoplas... Peritoneal Meta...	Pressurized Int...	18 Years - 80 Years	Seoul National University Bundang Hospital

Spots Global Cancer Trial Database for pressurized intraperitoneal aerosol chemotherapy