PIPAC With Nab-paclitaxel and Cisplatin in Peritoneal Carcinomatosis (Nab-PIPAC)

A Phase Ib Trial of Intraperitoneal Cisplatin and Nab-paclitaxel Administered by Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in the Treatment of Advanced Malignancies Confined to the Peritoneal Cavity

Phase Ib trial including investigating the combination of nab-paclitaxel and cisplatin in patients diagnosed with peritoneal carcinomatosis related to pancreatic, oeso-gastric, ovarian cancer or primitive peritoneal mesothelioma.

Study Overview

• Status: Recruiting
• Conditions: Peritoneal Carcinomatosis
• Intervention / Treatment: Drug: Nab paclitaxel; Drug: Cisplatin

Detailed Description

Phase Ib trial investigating the combination of intraperitoneal Cisplatin (10.5 mg/m2) and Nab-paclitaxel (escalated dose from 7.5 mg/m2 to 70 mg/m2) administered by pressurized intraperitoneal aerosol chemotherapy (PIPAC) every 4-6 weeks for 3 cycles.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Intidhar Labidi-Galy, MD, PhD; Phone Number: 0041 22 372 4014; Email: intidhar.labidi-galy@hcuge.ch
• Study Contact Backup: Name: Catherine Raimond, PharmD; Phone Number: 0041 22 37 22 908; Email: catherine.raimond@hcuge.ch

Study Locations

• Switzerland
  • Geneva, Switzerland, 1211
    • Recruiting
    • University Hospital, Geneva
    • Contact: Intidhar Labidi-Galy, MD, PhD; Phone Number: 0041 22 372 4014; Email: intidhar.labidi-galy@hcuge.ch
    • Contact: Catherine Raimond, PharmD; Phone Number: 0041 22 37 22 908; Email: catherine.raimond@hcuge.ch
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Recruiting
      • University Hospital, Lausanne
      • Contact: Antonella Diciolla, MD; Phone Number: 0041 79 55 63 011; Email: Antonella.Diciolla@chuv.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Informed consent as documented by signature
• ≥18 years,
• psychologically able to follow the trial procedures
• with peritoneal carcinomatosis from pancreatic, oesogastric, epithelial ovarian cancers or primitive peritoneal mesothelioma,
• ECOG 0, 1 or 2,
• Life expectancy > 3 months,
• Not candidate for surgical cytoreduction and IP/HIPEC based on expert multidisciplinary board
• who received at least one line of chemotherapy and for whom standard therapies have been exhausted or not feasible. patients with residual disease following the first line of therapy or Following secondary debulking are eligible.

Exclusion criteria:

• Predominant extra-peritoneal metastases at the discretion of the study team after discussion at the multidisciplinary board,
• Bowel obstruction, active gastro-duodenal ulcer or ongoing abdominal infection (bacterial, viral or fungal),
• Chemotherapy or surgery within the last two weeks prior to enrollment,
• Previous intra-abdominal chemotherapy,
• General or local (abdominal) contra-indications for laparoscopic surgery
• Known allergy to cisplatin or other platinum-containing compounds or to nab-paclitaxel,
• Severe renal impairment (calculated GFR (CKD-EPI) < 60 mL/min/1.73 m2), myelosuppression (platelet count < 100.000/μl, hemoglobin < 9g/dl, neutrophil granulocytes < 1.500/ml), International Normalized Ratio (INR) > 2, severe hepatic (Serum total bilirubin > 1.5 mg/dl), respiratory or neurologic impairment (grade 3), severe myocardial insufficiency (NYHA class > 2), recent myocardial infarction, severe arrhythmias,
• Pregnancy or breastfeeding, women who can become pregnant must ensure effective contraception.
• Known or suspected non-compliance, inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; Pressurized intraperitoneal aerosol chemotherapy (PIPAC) administration of Nab paclitaxel and cisplatin	Drug: Nab paclitaxel; Dose escalation (7.5 mg/m2, 15 mg/m2, 25 mg/m2, 37.5 mg/m2, 52.5 mg/m2 and 70 mg/m2); Drug: Cisplatin; 10.5 mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the maximal tolerated dose (MTD) of Nab paclitaxel (Abraxane®) administered IP by PIPAC in concomitance with cisplatin.	MTD is defined as the lowest dose level at which ≥33% of patients' experience dose limiting toxicity in accordance to CTCAE version 5.0 criteria.	From the time of treatment randomization through 30 days following cessation of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AE) and serious adverse events (SAE)	AE and SAE with predefined toxicity criteria will be applied using CTCAE version 5.0 criteria, documented before and after each cycle of PIPAC treatment. Surgical complications will be assessed according to Clavien classification and comprehensive complication index (CCI)	D-1/D10 of each cycle
The efficacy	It will be assessed by the objective histological regression and objective tumor response rate (OTR) according to the new regression system for peritoneal cancer (PRGS, peritoneal regression grade score system). The objective response rate (ORR), the clinical benefit rate (CBR) as defined by RECIST version 1.1 criteria and the relevance of radiological response assessed by CT enterography (CT-PCI score).	D0 of each cycle
The QoL	QoL will be evaluated based on the EORTC questionnaire QLQ-C30 Version 3.0 and visual analogic scale for pain (VAS scale).	D-1/D10 of each cycle

Collaborators and Investigators

• Sponsor: University Hospital, Geneva
• Investigators: Principal Investigator: Intidhar Labidi-Galy, MD, PhD, University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: May 29, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (Actual): June 27, 2019

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: pancreatic cancer; oeso-gastric cancer; epithelial ovarian cancer; primitive peritoneal mesothelioma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Digestive System Neoplasms; Abdominal Neoplasms; Carcinoma; Peritoneal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin
• Other Study ID Numbers: 2018-01327-Nab-PIPAC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The only clinical data available to researchers will be anonymised. Requests may be directed to Sponsor Investigator or designee. The informed consent form and clinical study report will be made available
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• IPD Sharing Access Criteria: All data supporting the findings of the current study will be made available from the corresponding author upon reasonable request.
• IPD Sharing Supporting Information Type: Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No