Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03304210
Other study ID # AGO/2017/003
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date September 16, 2017
Est. completion date May 6, 2020

Study information

Verified date January 2023
Source University Hospital, Ghent
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 20
Est. completion date May 6, 2020
Est. primary completion date May 6, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

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.

Locations

Country Name City State
Belgium UZ Ghent Ghent East-Flanders

Sponsors (7)

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

Country where clinical trial is conducted

Belgium, 

References & Publications (2)

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 meta — View 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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.
Within 14 weeks of the start of the treatment
Secondary 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 6 months after third PIPAC
Secondary Maximum Plasma Concentration of Abraxane 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
Secondary Area Under The Curve (AUC) of Abraxane 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
Secondary 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.
T = 0 minutes, before nebulization
Secondary 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 Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
Secondary 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. Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
See also
  Status Clinical Trial Phase
Terminated NCT04826432 - Pasireotide to Reduce Clinically Relevant Digestive Leakage After Complete Cytoreductive Surgery (CRS) Plus Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) for Peritoneal Carcinomatosis Phase 2
Recruiting NCT03127774 - Surgery and Heated Intraperitoneal Chemotherapy for Adrenocortical Carcinoma Phase 2
Recruiting NCT04024917 - Impact of Cardiac Coherence on Anxiety in Patients Operated on for a Peritoneal Carcinosis N/A
Active, not recruiting NCT03508570 - Nivolumab With or Without Ipilimumab in Treating Patients With Recurrent or High Grade Gynecologic Cancer With Metastatic Peritoneal Carcinomatosis Phase 1
Not yet recruiting NCT04352894 - Intraoperative ICG Fluorescence Imaging for Peritoneal Carcinomatosis Detection N/A
Terminated NCT01683864 - Randomized Controlled Trial to Prevent Peritoneal Seeding in Gastric Cancer Phase 2/Phase 3
Completed NCT06318793 - Preoperative Inflammatory Markers Predict Postoperative Complications After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Colorectal Carcinomatosis
Completed NCT05547568 - A Nomogram to Predict Major Postoperative Complications After Cytoreductive Surgery and HIPEC Based on Pre and Peroperative Criteria: Which Patient Require Intensive Monitoring?
Recruiting NCT04547725 - Complete Cytoreduction Followed by IP and Systemic Chemotherapies for Gastric Cancer With Peritoneal Carcinomatosis N/A
Withdrawn NCT03682744 - CAR-T Intraperitoneal Infusions for CEA-Expressing Adenocarcinoma Peritoneal Metastases or Malignant Ascites (IPC) Phase 1
Terminated NCT04047771 - A Phase I Study Evaluating SCB-313 for the Treatment of Subjects With Peritoneal Carcinomatosis Phase 1
Recruiting NCT05623787 - Diagnostic Value of Diffusion-weighted Magnetic Resonance in High-risk Colorectal and Appendiceal Neoplasms N/A
Recruiting NCT05063019 - Role of Magnetic Resonance Enterography for Predicting Peritoneal Cancer Index N/A
Completed NCT02891447 - Heated Mitomycin and Cisplatin During Surgery in Treating Patients With Stomach or Gastroesophageal Cancer Phase 2
Recruiting NCT04231175 - Dedicated MR Imaging vs Surgical Staging of Peritoneal Carcinomatosis in Colorectal Cancer N/A
Not yet recruiting NCT04734691 - Second Line Oxaliplatin Based Chemotherapy Alone Versus Oxaliplatin Based PIPAC and Chemotherapy in Colorectal Peritoneal Carcinomatosis : A Phase II Randomize Mutli-centric Study Phase 2
Recruiting NCT04108936 - Longitudinal Study of CRS/HIPEC for Peritoneal Carcinomatoses
Completed NCT02604784 - Study of Efficacy and Safety of Laparoscopic Intra-abdominal Chemotherapy (PIPAC) Performed in Patients With Peritoneal Carcinomatosis From Colorectal, Ovarian, Gastric Cancer and Primary Peritoneal Tumors Phase 1/Phase 2
Completed NCT01764789 - Stress Reduction in Improving Quality of Life in Patients With Recurrent Gynecologic or Breast Cancer N/A
Terminated NCT01540344 - Combined Anticancer Treatment of Advanced Colon Cancer Phase 2