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2017-09-16
2020-05-06
2020-05-06
20
NCT03304210
University Hospital, Ghent
University Hospital, Ghent
INTERVENTIONAL
PIPAC Nab-pac 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.
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.
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 Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2017-09-11 | 2022-01-10 | 2023-01-20 |
2017-10-02 | 2023-01-20 | 2023-11-07 |
2017-10-06 | 2023-11-07 | 2023-01 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Randomized
Interventional Model:
Single Group
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
|
| EXPERIMENTAL: Abraxane 70 mg/m² PIPAC with Abraxane (70 mg/m²) will be administered every 4 weeks for 3 cycles. | DRUG: PIPAC with Abraxane
|
| EXPERIMENTAL: Abraxane 90 mg/m² PIPAC with Abraxane (90 mg/m²) will be administered every 4 weeks for 3 cycles. | DRUG: PIPAC with Abraxane
|
| 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
|
| EXPERIMENTAL: Abraxane 140 mg/m² PIPAC with Abraxane (140 mg/m²) will be administered every 4 weeks for 3 cycles. | DRUG: PIPAC with Abraxane
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| 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 Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
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.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
NPCF was founded on May 29, 2009 and is a 501(c)(3) organization. All donations are tax deductible.
The information and services provided by the National Pancreatic Cancer Foundation are for informational purposes only. The information and services are not intended to be substitutes for professional medical advice, diagnosis or treatment. The National Pancreatic Cancer Foundation does not recommend nor endorse any specific physicians, products or treatments even though they may be mentioned on this site.
