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Trial record 1 of 1 for:    NCT02320448
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Treating Peritoneal Carcinomatosis With PIPAC

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ClinicalTrials.gov Identifier: NCT02320448
Recruitment Status : Completed
First Posted : December 19, 2014
Last Update Posted : September 12, 2017
Sponsor:
Information provided by (Responsible Party):
Michael Bau Mortensen, Odense University Hospital

Tracking Information
First Submitted Date  ICMJE December 9, 2014
First Posted Date  ICMJE December 19, 2014
Last Update Posted Date September 12, 2017
Actual Study Start Date  ICMJE March 2015
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
Number of Patients with Adverse Events. [ Time Frame: 5 months. ]
No patients with adverse events above grade 3 on the CTCAE (Version 4) scale. No patients with complications above grade 2 on the Dindo-Clavien classification.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02320448 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2016)
  • Occupational health. [ Time Frame: 5 months. ]
    No detectable chemotherapy on environmental biomonitoring and blood samples from the surgeons and OR staff.
  • Feasibility: Completion of procedure in 28:35 [ Time Frame: 5 months. ]
    Completion of procedure in 28:35.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
  • Occupational health. [ Time Frame: 5 months. ]
    No detectable chemotherapy on environmental biomonitoring and blood samples from the surgeons and OR staff.
  • Feasibility: Completion of procedure in 7:10 [ Time Frame: 5 months. ]
    Completion of procedure in 7:10.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treating Peritoneal Carcinomatosis With PIPAC
Official Title  ICMJE Implementation and Evaluation of PIPAC for the Treatment of Patients With Peritoneal Carcinomatosis - a Feasibility Study.
Brief Summary This is a feasibility study that aims to evaluate whether PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) is a safe and feasible treatment in Danish patients with peritoneal cancer.
Detailed Description

Peritoneal carcinomatosis (PC) represents end stage disease in many types of cancer (e.g. gastric, pancreatic, liver, colo-rectal, ovarian) and the majority of patients with PC will die from their disease within 6 months. Platinum-based systemic chemotherapy (SC) may prolong survival in selected patients, but poor performance status and low response rates have led to conservative (nihilistic) treatment strategies in these patients. However, patients with PC who are in good condition, and with a remaining life expectancy of more than a few months, may still have an unmet need for additional treatment in order to be able to perform with a high quality of life for as long as possible. These patients often have tried several lines of SC with disappointing results, and alternative and more effective treatment strategies are desperately needed.

The installation of chemotherapeutic agents within the peritoneal cavity would seem a simple and effective treatment of PC - at least from a theoretical point of view. Unfortunately, the effect of intraperitoneal chemotherapy on PC is disappointing. Like with SC, the poor response rates may be explained by the poor penetration of the active chemical substances into the PC plaques. Combining cytoreductive surgery (CRS) with intraperitoneal chemotherapy has gained interest in the recent years, but this approach can only be used in highly selected patients (where CRS is possible), and the procedure carries a significant risk of complications and side effects. Thus, a minimally invasive and safe delivery of relevant chemotherapy in such concentration that may allow it to work efficiently on the PC plaques would be an ideal platform for a new treatment strategy in these patients.

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) 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 micro-pump for safe aerosol infusion, a German research group has designed a system that allows a laparoscopy controlled, intraperitoneal aerosol infusion of chemotherapy (doxorubicin and cisplatin). The aerosol technique ensures that the entire peritoneal surface is covered by chemotherapy, and this is relevant in patients with PC. With the micro-pump positioned through a standard trocar pointing away from the bowels, a commercially available injection pump 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 intra-abdominal air saturated with chemotherapy is evacuated through a standard trocar.

Recently, a German research group published their preliminary experience with PIPAC in gastric and ovarian cancer patients with PC .

PIPAC is not available freely on the market, and the procedure is not FDA approved yet. The German research team has emphasized, that despite the very encouraging results obtained so far, the efficacy and safety of PIPAC still has to be assessed in adequate clinical trials.

Aim In a compassionate use program, the aim of this study is to implement and evaluate the PIPAC procedure at Odense University Hospital under strict observation of both patient and occupational health safety aspects. Thus, it is important to emphasize, that the primary aim of this feasibility study is a quick and safe implementation of a new combined surgical-oncologic treatment technique which uses conventional chemotherapy in a new way in desperately ill cancer patients. For technical and safety reasons this implementation needs to be fulfilled and documented before patients can be enrolled in clinical trials.

Hypothesis The investigators expect the PIPAC procedure to be feasible and safe, with a primary non-access ratio of maximum 7:35 (mainly due to adhesions). The investigators expect a CTCAE grade of no more than 3 and that the procedure is safe for both patients, surgeons and OR staff.

Method

Study design This is a feasibility study where the PIPAC procedure will be performed in 35 patients fulfilling the inclusion criteria.

Implementation of the PIPAC procedure In order to cover all safety aspects and to secure optimal treatment results, a complete manual and checklist for the entire PIPAC procedure, as well as for pre- and postoperative patient handling, has been made. Thus, every step of the procedure is carefully described and monitored, and prior to the first patient treatment, the entire PIPAC procedure will be tried in a "dummy" OR setup supervised by the German group. Although this group has documented, that the procedure is safe for both patients and health care workers, the procedure will only be performed in an OR with laminar airflow and a closed carbon dioxide (CO2) ventilation system. In addition, environmental measurements (platinum particles within the OR) and bio-monitoring (blood samples) of the OR team are scheduled from the beginning of the first PIPAC procedure.

Preliminary clinical evaluation 35 patients with PC (see inclusion criteria) will be scheduled for PIPAC. In collaboration with the German group, the local multidisciplinary team (MDT) meeting will carefully select patients suitable for the PIPAC procedure. These patients are included according to national regulations and rules on experimental cancer research. All PIPAC procedures are performed with prophylactic antibiotics and start with a classification of the extent of the PC (Peritoneal Cancer Index, PCI) followed by selected quadrant biopsies to document malignancy and for later translational research. The type and doses of chemotherapy (1/10 of systemic dose), intra-abdominal pressure, temperature and delivery time are similar to those used by the German group. After the PIPAC procedure, the patients will be observed for two days before discharge. The treatment response is monitored by CT, and by a follow-up laparoscopy procedure with PCI score and biopsies after six weeks. The PIPAC procedure will be repeated during the same evaluation laparoscopy if objective response or no progression is observed. Adverse medical events will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0), and surgical related complications according to the Dindo-Clavien classification.

Intra-abdominal access and completion of the PIPAC procedure in 28 of 35 patients and discharge of the same group within 2 POD are considered a successful implementation of the PIPAC procedure.

Occupational health safety aspects For safety reasons no staff is in the OR during the PIPAC procedure. The injector is controlled by a footswitch from outside the OR room, and observation monitors related to the anesthesiology are also made visible from outside the OR. Since no personnel are inside the ventilated OR room during application of the aerosolized chemotherapy, there are three barriers between surgeons/OR staff and the chemotherapy: The closed abdominal cavity, the laminar airflow system and the OR walls. The tightness of the abdominal cavity is controlled by allowing a maximum CO2 flow of 0.1-0.2 L/min corresponding to the body resorption of CO2. After the procedure, intraabdominal air saturated with chemotherapy is evacuated through a series of filters and into a closed system. Closure of the trocar sites, removal and disposal of dressings and syringes into special chemotherapy waste bins are performed by the surgeon alone. Environmental biomonitoring and blood samples from the surgeons and OR staff are scheduled as part of the safety monitoring.

Patient safety All patients are carefully selected (see exclusion criteria) on the MDT. The establishing of pneumoperitoneum and use of trocars are based on the highest standards for laparoscopic surgery which have a high safety profile. The procedures are performed by experienced laparoscopic surgeons under the supervision of the German team. When following the safety protocol used by the German group, no mortality related to the PIPAC procedure has been observed. The risk of bowel perforation is 2 per mille, port site metastases occur in 0.6% of the procedures, and self- limiting erythema around the trocar site is found in 1.2% of the procedures (private communication, professor Marc A. Reymond).

A short period of postoperative fever and/or elevated acute phase proteins have been observed after the PIPAC procedure, but the majority of patients may be discharged the same or the following day, and the PIPAC procedure can be repeated several times.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Peritoneal Carcinomatosis
Intervention  ICMJE Drug: PIPAC
Other Names:
  • Cisplatin
  • Doxorubicin
  • Oxaliplatin
Study Arms  ICMJE Experimental: PIPAC

PIPAC with cisplatin (7.5mg/m2 in 150 ml saline) and doxorubicin (1.5mg/m2 in 50 ml saline) in patients with peritoneal metastases (PM) from any origin besides colorectal/appendiceal cancers in whom oxaliplatin (92mg/m2 in 150 ml dextrose) will be used.

The aerosolised chemotherapy will be nebulized at a flow of 0.5ml/min at a maximum pressure of 200 PSI during a standard laparoscopy with an intraabdominal pressure of 12mmHg. The CO2 will be evacuated 30 minutes after administration of chemotherapy and the patient is closed similar to a standard laparoscopy.

Intervention: Drug: PIPAC
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 10, 2016)
35
Original Estimated Enrollment  ICMJE
 (submitted: December 18, 2014)
10
Actual Study Completion Date  ICMJE August 2017
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria

  • Histological or cytological verified malignancy.
  • Clinical or radiological evidence of peritoneal carcinomatosis.
  • No indication for standard chemotherapy.
  • Performance status 0-2 and life expectancy of more than 3 months.
  • Age > 18 years.
  • Written informed consent must be obtained according to the local Ethics Committee requirements.

Exclusion criteria

  • Symptomatic small bowel obstruction (Total parenteral nutrition, nasogastric tube).
  • Previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones.
  • A history of allergic reaction to cisplatin or other platinum containing compounds or doxorubicin.
  • Renal impairment, defined as GFR < 50 ml/min, (Cockcroft-Gault Equation).
  • Myocardial insufficiency, defined as NYHA class > 2.
  • Impaired liver function defined as bilirubin ≥ 1,5 x UNL (upper normal limit).
  • Inadequate haematological function defined as ANC ≤ 1.5 x 109/l and platelets ≤ 100 x 109/l.
  • Any other condition or therapy, which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives.
  • Previous intraabdominal chemotherapy or intraabdominal antibody therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02320448
Other Study ID Numbers  ICMJE PIPAC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Michael Bau Mortensen, Odense University Hospital
Study Sponsor  ICMJE Michael Bau Mortensen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michael Mortensen, Professor Odense University Hospital
PRS Account Odense University Hospital
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP