PIPAC Nab-pac for Stomach, Pancreas, Breast and Ovarian Cancer (PIPAC-nabpac)

January 20, 2023 updated by: University Hospital, Ghent

Intraperitoneal Aerosolization of Albumin-stabilized Paclitaxel Nanoparticles for Stomach, Pancreas, Breast and Ovarian Cancer

The PIPAC nab-pac study is designed to examine the maximal tolerated dose of albumin bound nanoparticle paclitaxel (nab-pac, Abraxane) administered with repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC), in a multicentre, multinational phase I trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Over 85% of women with ovarian cancer (OC) will develop a peritoneal recurrence after initial therapy. The prognosis of patients with recurrent disease is poor, with a median survival ranging from 12 to 24 months. Most of these patients ultimately develop platinum resistant disease (PROC). Current systemic therapy results in a very modest improvement of progression free and overall survival. The addition of locoregional, intraperitoneal (IP) therapy may improve disease control in recurrent OC. Recently, pressurized intraperitoneal aerosol therapy (PIPAC) was added to the therapeutic arsenal. This novel technique allows repeated laparoscopy aided aerosol delivery of anticancer drugs to the peritoneal cavity. Abraxane (nab-pac, Celgene) is a novel 130 nm, albumin-bound (nab) nanoparticle formulation of paclitaxel which has noteworthy single-agent activity and a favourable toxicity profile when used systemically in PROC. A recent phase I study showed a significant pharmacokinetic advantage after IP instillation of nab-pac in patients with peritoneal carcinomatosis from ovarian or gastro-intestinal (GI) origin.

In phase I of this study, dose escalation will be combined with pharmacokinetic/pharmacodynamic modelling which incorporates, in addition to plasma, tumour tissue, and peritoneal drug concentrations, biomarkers of toxicity and efficacy.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
    • East-Flanders
      • Ghent, East-Flanders, Belgium, 9000
        • UZ Ghent

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Phase I study: patients with advanced carcinomatosis from ovarian, breast, gastric, or pancreatic origin. No alternative systemic treatment options are available.
  • Age over 18 years
  • Adequate performance status (Karnofsky index > 60%)
  • Absence of intestinal or urinary obstruction
  • Limited size of the majority of peritoneal tumor implants (< 5 mm)
  • Absent or limited ascites
  • Ability to understand the proposed treatment protocol and provide informed consent
  • Expected life expectancy more than 6 months

  • Laboratory data

    • Serum creatinine ≤ 1.5 mg/dl or a calculated GFR (CKD-EPI) ≥ 60 mL/min/1.73 m²
    • Serum total bilirubin ≤ 1.5 mg/dl, except for known Gilbert's disease
    • Platelet count > 100.000/µl
    • Hemoglobin > 9g/dl
    • Neutrophil granulocytes > 1.500/ml
    • No major blood coagulation disorders. Parameters within normal range.
  • Absence of alcohol and/or drug abuse
  • No other concurrent malignant disease
  • Written informed consent

Exclusion Criteria:

  • Pregnancy or breast feeding. Women who can become pregnant must ensure effective contraception.
  • Active bacterial, viral or fungal infection
  • Active gastro-duodenal ulcer
  • Parenchymal liver disease (any stage cirrhosis)
  • Uncontrolled diabetes mellitus
  • Psychiatric pathology affecting comprehension and judgement faculty
  • General or local (abdominal) contra-indications for laparoscopic surgery
  • Documented intolerance or allergy to paclitaxel
  • Patients who receive other taxane therapy until three weeks before the first experimental treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Abraxane 35 mg/m²
PIPAC with Abraxane (35 mg/m²) will be administered every 4 weeks for 3 cycles.
Drug: PIPAC with Abraxane
Albumin bound nanoparticle paclitaxel (Abraxane) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 35 to 140 mg/m². PIPAC will be performed every 4 weeks for 3 cycles.
Experimental: Abraxane 70 mg/m²
PIPAC with Abraxane (70 mg/m²) will be administered every 4 weeks for 3 cycles.
Drug: PIPAC with Abraxane
Albumin bound nanoparticle paclitaxel (Abraxane) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 35 to 140 mg/m². PIPAC will be performed every 4 weeks for 3 cycles.
Experimental: Abraxane 90 mg/m²
PIPAC with Abraxane (90 mg/m²) will be administered every 4 weeks for 3 cycles.
Drug: PIPAC with Abraxane
Albumin bound nanoparticle paclitaxel (Abraxane) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 35 to 140 mg/m². PIPAC will be performed every 4 weeks for 3 cycles.
Experimental: Abraxane 112.5 mg/m²
PIPAC with Abraxane (112.5 mg/m²) will be administered every 4 weeks for 3 cycles.
Drug: PIPAC with Abraxane
Albumin bound nanoparticle paclitaxel (Abraxane) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 35 to 140 mg/m². PIPAC will be performed every 4 weeks for 3 cycles.
Experimental: Abraxane 140 mg/m²
PIPAC with Abraxane (140 mg/m²) will be administered every 4 weeks for 3 cycles.
Drug: PIPAC with Abraxane
Albumin bound nanoparticle paclitaxel (Abraxane) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 35 to 140 mg/m². PIPAC will be performed every 4 weeks for 3 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximally Tolerated Dose (MTD) of Abraxane
Time Frame: Within 14 weeks of the start of the treatment

The MTD was defined as the highest dose of aerosolized Abraxane, administered 3 times using PIPAC, that does not cause unacceptable side effects. Dose limiting toxicity was recorded in a 14 week-window starting from the first PIPAC and defined a priori as any of the following: 1. any Grade 3 or 4 non-hematologic toxicity excluding fatigue and controllable nausea, vomiting, abdominal pain, and diarrhoea; 2. grade 4 thrombocytopenia; 3. grade 4 neutropenia lasting more than 7 days or associated with fever; 4. failure to perform more than one PIPAC due to toxicity; 5. surgical complication Dindo-Clavien grade IIIB or higher.

In order to optimize the balance between safety and efficacy, we used a time-to-event continual reassessment model (TITE-CRM), where an initial design was followed until the first DLT occurred. Conservative a priori estimates of DLT were used to calculate the original dose escalation scheme.
Within 14 weeks of the start of the treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under The Curve (AUC) of Abraxane
Time Frame: T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours
Abraxane will be measured in plasma, using LC-MS/MS.
T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours
Surgical Morbidity
Time Frame: 6 months after third PIPAC
Surgical complications were scored using the Clavien Dindo classification. Grade I: Any deviation from the normal post-operative course not requiring surgical, endoscopic or radiological intervention. This includes the need for certain drugs (e.g. antiemetics, antipyretics, analgesics, diuretics and electrolytes), treatment with physiotherapy and wound infections that are opened at the bedside Grade II: Complications requiring drug treatments other than those allowed for Grade I complications; this includes blood transfusion and total parenteral nutrition (TPN) Grade III: Complications requiring surgical, endoscopic or radiological intervention Grade IV: Life-threatening complications; this includes CNS complications (e.g. brain haemorrhage, ischaemic stroke, subarachnoid haemorrhage) which require intensive care, but excludes transient ischaemic attacks (TIAs) Grade V: Death of the patient
6 months after third PIPAC
Maximum Plasma Concentration of Abraxane
Time Frame: T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours
Abraxane will be measured in plasma, using UPLC-MS/MS.
T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours
Histological Response Via Peritoneal Regression Grading Scoring (PRGS)
Time Frame: T = 0 minutes, before nebulization

Punch biopsies are taken at the same location, which are marked with a stainless-steel surgical clip during each PIPAC procedure. Samples are fixed in 4% paraformaldehyde in PBS for 72 hours and embedded in paraffin. Tissues are serially sectioned and stained with haematoxylin & eosin; immunohistochemical staining is performed for epithelial cellular adhesion molecule (EpCAM). The peritoneal regression grading score (PRGS) is determined by a GI pathologist.

The mean score of all samples is calculated per treatment, and percentage changes in mean PRGS between successive PIPAC treatments is calculated. The unit of measure represented is the amount of participants in which tumor regression was observed.
T = 0 minutes, before nebulization
Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Time Frame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
Blood samples will be collected to analyse the absolute neutrophil count
Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Time Frame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
Blood samples will be collected to analyse the amount of platelets.
Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Ghent

Collaborators

Centre Hospitalier Universitaire Vaudois
University Ghent
Hopital Lariboisière
Kom Op Tegen Kanker
Candiolo Cancer Institute - IRCCS
University Women's Hospital Tübingen

Investigators

  • Principal Investigator: Wim P Ceelen, MD, PhD, Prof, University Hospital, Ghent

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 16, 2017

Primary Completion (Actual)

May 6, 2020

Study Completion (Actual)

May 6, 2020

Study Registration Dates

First Submitted

September 11, 2017

First Submitted That Met QC Criteria

October 2, 2017

First Posted (Actual)

October 6, 2017

Study Record Updates

Last Update Posted (Actual)

November 7, 2023

Last Update Submitted That Met QC Criteria

January 20, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AGO/2017/003

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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