Breast Cancer Stage IIIB, Breast Cancer Stage IIIc, Breast Cancer Stage IV, Ovarian Cancer Stage IIIB, Ovarian Cancer Stage IIIC, Ovarian Cancer Stage IV, Pancreas Cancer, Stage III, Pancreas Cancer, Stage IV, Peritoneal Carcinomatosis, Stomach Cancer Stage III, Stomach Cancer Stage IV With Metastases
Conditions
Keywords
PIPAC, Peritoneal carcinomatosis, Ovarian cancer, Pharmacokinetics, Pharmacodynamics, Safety and efficacy, Abraxane, Breast cancer, Pancreas cancer, Stomach cancer
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.
Interventions
DRUGPIPAC 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.
Sponsors
Kom Op Tegen Kanker
University Ghent
Hopital Lariboisière
University Women's Hospital Tübingen
Candiolo Cancer Institute - IRCCS
Centre Hospitalier Universitaire Vaudois
University Hospital, Ghent
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximally Tolerated Dose (MTD) of Abraxane | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration of Abraxane | 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. |
| Area Under The Curve (AUC) of Abraxane | 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. |
| Surgical Morbidity | 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 |
| Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC | Blood samples will be collected to analyse the absolute neutrophil count |
| Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC | Blood samples will be collected to analyse the amount of platelets. |
| Histological Response Via Peritoneal Regression Grading Scoring (PRGS) | 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. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abraxane 35 mg/m² PIPAC with Abraxane (35 mg/m²) will be administered every 4 weeks for 3 cycles.
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. | 2 |
| Abraxane 70 mg/m² PIPAC with Abraxane (70 mg/m²) will be administered every 4 weeks for 3 cycles.
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. | 2 |
| Abraxane 90 mg/m² PIPAC with Abraxane (90 mg/m²) will be administered every 4 weeks for 3 cycles.
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. | 3 |
| Abraxane 112.5 mg/m² PIPAC with Abraxane (112.5 mg/m²) will be administered every 4 weeks for 3 cycles.
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. | 3 |
| Abraxane 140 mg/m² PIPAC with Abraxane (140 mg/m²) will be administered every 4 weeks for 3 cycles.
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. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Abraxane 35 mg/m² | Abraxane 70 mg/m² | Abraxane 90 mg/m² | Abraxane 112.5 mg/m² | Abraxane 140 mg/m² | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 3 Participants | 2 Participants | 9 Participants | 15 Participants |
| Age, Continuous | 64 years | 68 years | 52 years | 59 years | 51 years | 57 years |
| Race and Ethnicity Not Collected | — | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 2 / 2 | 1 / 3 | 1 / 3 | 1 / 10 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 3 / 3 | 3 / 3 | 10 / 10 |
| serious Total, serious adverse events | 2 / 2 | 2 / 2 | 2 / 3 | 1 / 3 | 6 / 10 |
Outcome results
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.
Time frame: Within 14 weeks of the start of the treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abraxane 35 mg/m² | Maximally Tolerated Dose (MTD) of Abraxane | 0 Participants |
| Abraxane 70 mg/m² | Maximally Tolerated Dose (MTD) of Abraxane | 0 Participants |
| Abraxane 90 mg/m² | Maximally Tolerated Dose (MTD) of Abraxane | 0 Participants |
| Abraxane 112.5 mg/m² | Maximally Tolerated Dose (MTD) of Abraxane | 0 Participants |
| Abraxane 140 mg/m² | Maximally Tolerated Dose (MTD) of Abraxane | 0 Participants |
Secondary
Area Under The Curve (AUC) of Abraxane
Abraxane will be measured in plasma, using LC-MS/MS.
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abraxane 35 mg/m² | Area Under The Curve (AUC) of Abraxane | 585 h*ng/mL | Standard Deviation 93 |
| Abraxane 70 mg/m² | Area Under The Curve (AUC) of Abraxane | 962 h*ng/mL | Standard Deviation 237 |
| Abraxane 90 mg/m² | Area Under The Curve (AUC) of Abraxane | 813 h*ng/mL | Standard Deviation 99 |
| Abraxane 112.5 mg/m² | Area Under The Curve (AUC) of Abraxane | 1658 h*ng/mL | Standard Deviation 465 |
| Abraxane 140 mg/m² | Area Under The Curve (AUC) of Abraxane | 2002 h*ng/mL | Standard Deviation 569 |
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.
Time frame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abraxane 35 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 0 Participants |
| Abraxane 35 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 0 Participants |
| Abraxane 35 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no thrombopenia | 2 Participants |
| Abraxane 70 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no thrombopenia | 1 Participants |
| Abraxane 70 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 0 Participants |
| Abraxane 70 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 1 Participants |
| Abraxane 90 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no thrombopenia | 1 Participants |
| Abraxane 90 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 1 Participants |
| Abraxane 90 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 1 Participants |
| Abraxane 112.5 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 0 Participants |
| Abraxane 112.5 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 2 Participants |
| Abraxane 112.5 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no thrombopenia | 1 Participants |
| Abraxane 140 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no thrombopenia | 7 Participants |
| Abraxane 140 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 0 Participants |
| Abraxane 140 mg/m² | Decreased Platelets - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 3 Participants |
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.
Time frame: T = 0 minutes, before nebulization
Population: Tumour tissue samples were taken from each abdominal quadrant (n = 4) before aerosol delivery. In 30% of all procedures, less than four biopsies (or none) were taken due to technical reasons (adhesions) or because no visible tumour was present, which explains the lower number of participants analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abraxane 35 mg/m² | Histological Response Via Peritoneal Regression Grading Scoring (PRGS) | 0 participants with tumor regression |
| Abraxane 70 mg/m² | Histological Response Via Peritoneal Regression Grading Scoring (PRGS) | 1 participants with tumor regression |
| Abraxane 90 mg/m² | Histological Response Via Peritoneal Regression Grading Scoring (PRGS) | 1 participants with tumor regression |
| Abraxane 112.5 mg/m² | Histological Response Via Peritoneal Regression Grading Scoring (PRGS) | 0 participants with tumor regression |
| Abraxane 140 mg/m² | Histological Response Via Peritoneal Regression Grading Scoring (PRGS) | 7 participants with tumor regression |
Secondary
Maximum Plasma Concentration of Abraxane
Abraxane will be measured in plasma, using UPLC-MS/MS.
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abraxane 35 mg/m² | Maximum Plasma Concentration of Abraxane | 58 ng/mL | Standard Deviation 15 |
| Abraxane 70 mg/m² | Maximum Plasma Concentration of Abraxane | 138 ng/mL | Standard Deviation 42 |
| Abraxane 90 mg/m² | Maximum Plasma Concentration of Abraxane | 101 ng/mL | Standard Deviation 13 |
| Abraxane 112.5 mg/m² | Maximum Plasma Concentration of Abraxane | 157 ng/mL | Standard Deviation 49 |
| Abraxane 140 mg/m² | Maximum Plasma Concentration of Abraxane | 184 ng/mL | Standard Deviation 68 |
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
Time frame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abraxane 35 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no neutropenia | 2 Participants |
| Abraxane 35 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 0 Participants |
| Abraxane 35 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 0 Participants |
| Abraxane 70 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 0 Participants |
| Abraxane 70 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 0 Participants |
| Abraxane 70 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no neutropenia | 2 Participants |
| Abraxane 90 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no neutropenia | 2 Participants |
| Abraxane 90 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 1 Participants |
| Abraxane 90 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 0 Participants |
| Abraxane 112.5 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no neutropenia | 2 Participants |
| Abraxane 112.5 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 1 Participants |
| Abraxane 112.5 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 0 Participants |
| Abraxane 140 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | no neutropenia | 5 Participants |
| Abraxane 140 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade <=2 | 4 Participants |
| Abraxane 140 mg/m² | Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | CTCAE grade >2 | 1 Participants |
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
Time frame: 6 months after third PIPAC
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abraxane 35 mg/m² | Surgical Morbidity | 2 participants |
| Abraxane 70 mg/m² | Surgical Morbidity | 2 participants |
| Abraxane 90 mg/m² | Surgical Morbidity | 3 participants |
| Abraxane 112.5 mg/m² | Surgical Morbidity | 3 participants |
| Abraxane 140 mg/m² | Surgical Morbidity | 10 participants |