Clinical trial NCT03304210: PIPAC Nab-pac for Stomach, Pancreas, Breast and Ovarian Cancer
Official title: Intraperitoneal Aerosolization of Albumin-stabilized Paclitaxel Nanoparticles for Stomach, Pancreas, Breast and Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Peritoneal Carcinomatosis
Ovarian Cancer Stage IIIB
Ovarian Cancer Stage IIIC
Ovarian Cancer Stage IV
Breast Cancer Stage IIIB
Breast Cancer Stage IIIc
Breast Cancer Stage IV
Stomach Cancer Stage III
Stomach Cancer Stage IV With Metastases
Pancreas Cancer, Stage III
Pancreas Cancer, Stage IV
Keywords: PIPAC
Peritoneal carcinomatosis
Ovarian cancer
Pharmacokinetics
Pharmacodynamics
Safety and efficacy
Abraxane
Breast cancer
Pancreas cancer
Stomach cancer
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: Kom Op Tegen Kanker
name: University Ghent
name: Hopital Lariboisière
name: University Women's Hospital Tübingen
name: Candiolo Cancer Institute - IRCCS
name: Centre Hospitalier Universitaire Vaudois
First posted: 2017-10-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximally Tolerated Dose (MTD) of Abraxane
timeFrame: Within 14 weeks of the start of the treatment
Secondary outcomes:
measure: Surgical Morbidity
timeFrame: 6 months after third PIPAC
measure: Maximum Plasma Concentration of Abraxane
timeFrame: 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
measure: Area Under The Curve (AUC) of Abraxane
timeFrame: 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
measure: Histological Response Via Peritoneal Regression Grading Scoring (PRGS)
timeFrame: T = 0 minutes, before nebulization
measure: Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
timeFrame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
measure: Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
timeFrame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: UZ Ghent
state: East-Flanders
Study officials:
affiliation: University Hospital, Ghent
name: Wim P Ceelen, MD, PhD, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.