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Peritoneal CarcinomatosisPhase 1PIPAC-nabpacNCT03304210

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

A Phase 1 study testing PIPAC with Abraxane in people with Peritoneal Carcinomatosis and Ovarian Cancer Stage IIIB, run by University Hospital, Ghent at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PIPAC with Abraxane
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteBelgium
Study dates
16 Sep 2017to 6 May 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 18Show fewer
  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Belgium1 site
  • UZ Ghent

    Ghent, East-Flanders, 9000

Other trials in Belgium

About this study

Official title: 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.

Read the 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.

Being tested
PIPAC with Abraxane
Keywords
PIPAC, Peritoneal carcinomatosis, Ovarian cancer, Pharmacokinetics, Pharmacodynamics, Safety and efficacy, Abraxane, Breast cancer, Pancreas cancer, Stomach cancer
Medical subject headings
Peritoneal Neoplasms, Ovarian Neoplasms, Breast Neoplasms, Stomach Neoplasms, Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PIPAC with AbraxaneDrug

    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.

Study groups in NCT03304210
Study groupRoleWhat they receive
Abraxane 35 mg/m²ExperimentalPIPAC with Abraxane (35 mg/m²) will be administered every 4 weeks for 3 cycles.
Receives: Drug: PIPAC with Abraxane
Abraxane 70 mg/m²ExperimentalPIPAC with Abraxane (70 mg/m²) will be administered every 4 weeks for 3 cycles.
Receives: Drug: PIPAC with Abraxane
Abraxane 90 mg/m²ExperimentalPIPAC with Abraxane (90 mg/m²) will be administered every 4 weeks for 3 cycles.
Receives: Drug: PIPAC with Abraxane
Abraxane 112.5 mg/m²ExperimentalPIPAC with Abraxane (112.5 mg/m²) will be administered every 4 weeks for 3 cycles.
Receives: Drug: PIPAC with Abraxane
Abraxane 140 mg/m²ExperimentalPIPAC with Abraxane (140 mg/m²) will be administered every 4 weeks for 3 cycles.
Receives: Drug: PIPAC with Abraxane

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximally Tolerated Dose (MTD) of Abraxane

    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.

    Measured: Within 14 weeks of the start of the treatment

Secondary outcomes (6)
  1. Surgical Morbidity

    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

    Measured: 6 months after third PIPAC

  2. Maximum Plasma Concentration of Abraxane

    Abraxane will be measured in plasma, using UPLC-MS/MS.

    Measured: 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

  3. Area Under The Curve (AUC) of Abraxane

    Abraxane will be measured in plasma, using LC-MS/MS.

    Measured: 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

  4. Histological Response Via Peritoneal Regression Grading Scoring (PRGS)

    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.

    Measured: T = 0 minutes, before nebulization

  5. Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

    Blood samples will be collected to analyse the absolute neutrophil count

    Measured: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC

  6. Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

    Blood samples will be collected to analyse the amount of platelets.

    Measured: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2017
  2. Study start16 Sep 2017
  3. Primary completion6 May 2020
  4. Study completion6 May 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03304210
Sponsor's protocol ID
AGO/2017/003
Acronym
PIPAC-nabpac
Status last verified
Jan 2023
First submitted
11 Sep 2017
Last updated
7 Nov 2023
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Van De Sande L, Graversen M, Hubner M, Pocard M, Reymond M, Vaira M, Cosyns S, Willaert W, Ceelen W. Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane) for peritoneal carcinomatosis - a phase I first-in-human study. Pleura Peritoneum. 2018 Jun 8;3(2):20180112. doi: 10.1515/pp-2018-0112. eCollection 2018 Jun 1.

    PubMed 30911657
  • Ceelen W, Sandra L, de Sande LV, Graversen M, Mortensen MB, Vermeulen A, Gasthuys E, Reynders D, Cosyns S, Hoorens A, Willaert W. Phase I study of intraperitoneal aerosolized nanoparticle albumin based paclitaxel (NAB-PTX) for unresectable peritoneal metastases. EBioMedicine. 2022 Aug;82:104151. doi: 10.1016/j.ebiom.2022.104151. Epub 2022 Jul 15.

    PubMed 35843174

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PIPAC with Abraxane in people with Peritoneal Carcinomatosis and Ovarian Cancer Stage IIIB, run by University Hospital, Ghent at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximally Tolerated Dose (MTD) of Abraxane (time frame: Within 14 weeks of the start of the treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03304210, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.

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