A Phase 2 interventional study of PIPAC in Peritoneum Cancer, Peritoneal Carcinomatosis and Peritoneal Metastases, sponsored by Michael Bau Mortensen. Recruiting at 1 site in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-10-06.
Sponsored by Michael Bau Mortensen · Phase 2, Interventional, and Prevention
In this study, patients will be offered two Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) treatments with oxaliplatin after primary resection and standard adjuvant chemotherapy (if indicated) for colon cancer. Furthermore, the study will explore, whether it is possible to find free intraperitoneal tumor cells (FITC) after resection and adjuvant chemotherapy for colon cancer.
In 2015, 3500 patients were diagnosed with colon cancer in Denmark (DCCG Årsrapport 2015, www.dccg.dk). Despite curative intended surgery and perioperative chemotherapy in colon cancers, relapse is often encountered, and across tumor stage recurrence is found in 18-26% of the resected patients. Eighty-six percent of the recurrences are diagnosed within three years after resection, and 36% of the recurrences are diagnosed within the first year regardless of tumor stage. The route of dissemination varies with different cancer types, but a common denominator is the risk of peritoneal metastases (PM). PM is the second most common site of recurrence in colon cancer patients, and accounts for 25-35% of all recurrences. Patients with PM - both in the synchronous and metachronous setting - will often have a very short life expectancy and traditionally, treatment have been nihilistic due to poor performance status and response rates, and most patients with recurrence to the peritoneum will only be treated with best supportive care. During the last two decades, more aggressive treatment strategies have been implemented, including extensive surgery (Cytoreductive surgery, CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). However, CRS and HIPEC are only used in selected patients with limited PM. High risk factors for relapse with PM have been identified, and patients with T4 colon cancers have a risk of relapse with metachronous PM between 12-50%, while patients with intraperitoneally perforated colorectal cancers relapse with PM in 14- 58% of the cases. The risk of metachronous PM in perforated or T4 colorectal cancers has been validated and this is widely recognized in the ongoing trials around Europe, where adjuvant HIPEC is being investigated in patients with high-risk colon tumors to prevent metachronous PM (www.clinicaltrials.gov NCT02231086, NCT02965248, NCT02614534, NCT02974556, NCT01226394).
In addition to tumor stage, free intraperitoneal tumor cells (FITC) are perceived as a precursor of PM, and it is expected, that patients with perforated/T4 colon cancers will have FITC prior to visible recurrence with PM. However, despite the reported impact on the risk of recurrence and poor survival data, the presence of FITC is not routinely investigated, and this may be due to the lack of treatment options regarding the eradication of free tumor cells. In a systematic review of resected patients with stage I-IV colorectal cancer, 13.7% had FITC detected during perioperative peritoneal lavage. The rate of FITC increased with increasing T-stage and the patients with FITC had a significantly increased risk of both local and overall recurrence, plus a significantly increased mortality risk.
Based on the above-mentioned rate of recurrences after resection of high-risk colon cancers and the limited treatment options, new treatment strategies are needed. A German research group has invented a new intraperitoneal chemotherapy delivery method, where the chemotherapy is nebulized within the pressurized abdominal cavity - Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC).
PIPAC As blood supply to the peritoneal surface is scarce, systemic chemotherapy has limited access to the peritoneal cavity, especially when the primary tumor including its exfoliating surface has been resected. Even though intraperitoneal chemotherapy would seem like a tempting alternative, convincing results are still missing. Temperature and pressure are important factors during absorption of fluid from the peritoneal cavity, and the use of a relative low intraperitoneal pressure (2-6 mmHg) seems to increase the inflow of intraperitoneal fluid into the abdominal wall. Studies have confirmed that higher tissue concentrations of chemotherapy may be obtained by increasing the intraperitoneal pressure. After years of extensive testing, and the development of a CE-certified nebulizer (CapnoPen, Capnomed, Villingendorf, Germany) for safe aerosol infusion, a German research group has designed a system that allows a laparoscopy controlled delivery of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). The aerosol technique ensures that the entire peritoneal surface is covered by chemotherapy, and this is relevant when trying to eradicate (all) free intraperitoneal tumor cells. With the nebulizer positioned through a standard trocar pointing away from the bowels, a commercially available injection pump (MEDRAD Salient Dual Contrast Injector, Bayer HealthCare, Leverkusen, Germany) provides the necessary pressure to induce an aerosol mist covering the peritoneal cavity. After five minutes, the chemotherapy has been delivered, and the injector is turned off. After an additional 25 minutes of simple diffusion, the aerosol is gone and the remaining intraabdominal CO2 is evacuated through a standard trocar.
PIPAC is safe, both for patients and healthcare workers, and preliminary data suggest encouraging objective tumor response and survival data. Based on the results of the German research group, PIPAC has been implemented at Odense University Hospital in a feasibility and safety study (www.clinicaltrial.gov NCT02320448, The Regional Scientific Ethical Committees for Southern Denmark Project-ID: S-20140211). Accrual has stopped, as the planned 35 patients have been included. 130 PIPAC treatments have been performed so far, and three patients are still in treatment. Preliminary data suggest a good safety profile, both in terms of patient safety and occupational health safety, as demonstrated on The First Scandinavian PIPAC Symposium, April 20th 2017. In brief, environmental and biological analyses demonstrated no risk of chemotherapy exposure to the health care workers, the planned procedures could be completed in 100% of the patients and 90% were discharged within the first postoperative day (range 1-4). In 20% of the procedures using oxaliplatin, the patients had postoperative urinary retention relieved by a singleuse catheter and in less than 5% of the procedures, a serious adverse event (CTCAE grade 3) was encountered (1 small bowel perforation, 1 small bowel obstruction, 1 cholestasis, 1 diarrhea), and there was no mortality.
Detection of FITC FITC is usually detected by analysing smears of sediment from the peritoneal lavage fluid collected during a staging laparoscopy or during the course of surgery. As FITC is routinely investigated in especially Asian gastric cancer patients, the current experience on the detection of FITC arises from studies in gastric cancer patients. A recent meta-analysis described the risk of peritoneal recurrence of gastric cancer, based on analysis of peritoneal lavage fluid. In this study, peritoneal lavage cytology predicted peritoneal recurrence with a sensitivity of only 0.45, while the specificity was 0.92-0.98. By the detection of carcinoembryonic antigen (CEA) in the peritoneal lavage fluid, the sensitivity was 0.77 and the specificity 0.89, whereas the analysis of CEA mRNA raised the sensitivity to 0.87, with a specificity of 0.80. In a systematic review, peritoneal lavage cytology predicted peritoneal recurrence of gastric cancer patients with a sensitivity of 0.11-0.80 and a specificity of 0.86-1.00. By analysing the lavage fluid with immunoassays, immunohistochemistry or Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) mainly towards CEA, the sensitivity and specificity still varied significantly (sensitivity 0.23-1.00, specificity 0.81-0.98). Despite the variable results, the included studies of this systematic review confirmed a significantly reduced median overall survival in patients with FITC. However, there is no standard definition of the techniques or cut off points used to detect FITC - neither in gastric/GEJ cancer patients nor in colon cancer patients.
Study rationale As PIPAC seems to have an effect on visible PM in colon cancer patients, the investigators hypothesize that PIPAC can minimize the risk of PM recurrence in resected high risk colon cancer patients.
Furthermore, the investigators expect that PIPAC can eradicate FITC in these patients.
Study population Danish patients with colon cancer are eligible candidates according to the inclusion criteria. The patients will be included after resection and, if indicated, adjuvant systemic chemotherapy. While expected accrual is based on the number of resected patients at Odense University Hospital, this study will include patients nationwide.
In 2015, 284 patients were resected due to colon cancer at Odense University Hospital (OUH). Ninety-three percent of the resections were with curative intent (n=264), and eighteen percent had T4 tumors (DCCG Årsrapport 2015, www.dccg.dk). Based on these data and according to the inclusion criteria, 47 patients are eligible candidates per year, and the expected accrual of 60 patients (see below) is two years.
249 studies on the registry are indexed under Peritoneal Neoplasms; 55 are open to participants now.
This study's planned enrollment of 60 is above the median of 46 across 202 interventional studies indexed under Peritoneal Neoplasms.
Browse Peritoneal Neoplasms studies →Michael Bau Mortensen is the lead sponsor of 8 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Eligible candidates will be enrolled according to in-/exclusion criteria. Two months after colon resection or immediately after adjuvant chemotherapy (if indicated), a standard laparoscopy including peritoneal lavage, peritoneal biopsies and PIPAC treatment with oxaliplatin 92 mg/m2 will be planned. This procedure will be repeated after another 5 weeks. Follow up CTs after 12, 24 and 36 months will be planned.
Drug: PIPAC
PIPAC is performed during a standard laparoscopy with a capnoperitoneum of 12 mmHg. During PIPAC, oxaliplatin 46 mg/m2 in 150 ml dextrose will be intraperitoneally nebulized at a rate of 0.5 ml/s with a maximum pressure of 200 PSI. The intraperitoneal air will be evacuated after 30 minutes of simple diffusion
Also known as: Oxaliplatin
The number of patients with peritoneal recurrence
Based on contrast enhanced CT of the thorax and abdomen 36 months after resection of high-risk colon cancer.
Time frame: 3 years
The number of conversions from positive to negative peritoneal lavage cytology
Peritoneal lavage cytology will be performed during each PIPAC treatment in order to detect free intraperitoneal tumor cells. Interval of 5 weeks between each PIPAC.
Time frame: 5 weeks
Number of patients where the planned PIPAC procedures are completed
Two PIPAC procedures are planned.
Time frame: 5 weeks
Number of patients with treatment related toxicity or complications
Based on CTCAE (vers. 4.0) and Dindo-Clavien´s surgical complications assessment.
Time frame: 3 months
1- and 2-year peritoneal recurrence free survival
Based on CT of the thorax and abdomen performed 12- and 24 months after primary resection
Time frame: 2 years
1-, 2- and 3-year recurrence free survival,
Based on CT of the thorax and abdomen performed 12-, 24 and 36 months after primary resection
Time frame: 3 years
1-, 3- and 5-year overall survival rate
Based on the Danish Civil Registration System
Time frame: 5 years
Plan to share: No — The database will be used for publications and presentations by the study group.
Started Dec 2017 (actual). Primary completion is estimated for Oct 2024, 81 months after the start.
Of 28 phase 2 interventional studies under Peritoneal Neoplasms, half reached primary completion within 62 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 96. This study's planned 81 months is above that.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Oxaliplatin
Michael Bau Mortensen