Clinical trial NCT05371223: Combined Nabpaclitaxel Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic Nabpaclitaxel-Gemcitabine Chemotherapy for Pancreatic Cancer Peritoneal Metastases
Official title: Combined Nabpaclitaxel Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic Nabpaclitaxel-Gemcitabine Chemotherapy for Pancreatic Cancer Peritoneal Metastases - A Single-arm, Open-label, Phase II Trial: Nab-PIPAC Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Peritoneal Carcinomatosis
Pancreas Neoplasm
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2022-05-12
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Combined chemotherapy consisting of endovenous Nabpaclitaxel-Gemcitabine and Nabpaclitaxel-PIPAC may be a promising treatment for patients affected by pancreatic cancer PM who are in need of curative options.

The purpose of this study is to evaluate the antitumoral activity of combined Nabpaclitaxel-PIPAC and systemic Nabpaclitaxel-Gemcitabine chemotherapy for pancreatic cancer peritoneal metastases.

Secondary objectives include the evaluation of the feasibility, the safety, further assessment of the antitumoral activity, the overall and progression free survival, the QoL, the pharmacokinetics of Nabpaclitaxel PIPAC.

Furthermore, the study aims to evaluate the patients' nutritional status and the molecular evolution of PM along treatment with a time-course translational research.

Detailed description: Pancreatic carcinoma (PC) is an aggressive neoplasm carrying a high metastatic potential with a 5-year survival rate of 7%. The vast majority of cases already developed locally advanced disease, and distant metastases are present at the time of diagnosis. Furthermore, the recurrence rate is nearly 80% within the first two years after surgery, and about half of these patients show peritoneal relapse. Palliative systemic chemotherapy represents the standard treatment option in case of peritoneal metastases (PM) from PC but roughly reaches a median overall survival of 6-11 months with more than 5% of serious adverse events.

Based on the available data, Nabpaclitaxel is indicated in combination with Gemcitabine for the first-line systemic treatment of patients with metastatic adenocarcinoma of the pancreas.

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a novel intraperitoneal drug-delivery system of low-dose chemotherapy as a pressurized aerosol. Until now, the combination cisplatin/doxorubicin or oxaliplatin has been administered by PIPAC. Recently, a phase I study (NCT03304210) was conducted to explore the use of intraperitoneal Nabpaclitaxel administered by PIPAC, confirming its safety and preliminary efficacy. The recommended dose to safely start a phase-II study was 112.5 mg/m2.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years;
* Willing and able to provide written and informed consent;
* Histological or cytological proof of pancreatic cancer;
* Metastatic disease with peritoneal carcinomatosis determined by the treating physician, based on abdominal CT or MR and/or diagnostic laparotomy or laparoscopy;
* Evaluable disease defined by RECIST 1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
* Life expectancy of at least 3 months;
* No contraindication for laparoscopy;
* No contraindication for drugs used in the study;
* Adequate bone marrow function: Absolute neutrophil count ≥ 1500 cell./mm3; Platelets ≥ 100000 cell./mm3;
* Hemoglobin ≥ 9 g/dl
* Adequate renal function (serum creatinine up to 1.5 times the maximal limit of the local laboratory) or else based upon clinical evaluation;

Exclusion Criteria:

* Advanced metastatic systemic disease with clinical deterioration;
* Patients with extraabdominal tumor spread;
* Patients with a germline or somatic pathogenic variant involving an (Homologous Recombination Repair) HRR-related gene;
* Symptoms of gastrointestinal occlusion and total parenteral nutritional support;
* Patients defined as "refractory" to previous systemic treatment with Nab-paclitaxel and Gemcitabine administered for locally advanced pancreatic cancer (patients treated with Nabpaclitaxel-Gemcitabine for a locally advanced disease may be included if PM developed after at least 6 months from the end of previous chemotherapy);
* History of severe and unexpected reactions to Nabpaclitaxel or Gemcitabine derivates
* Known hypersensitivity reaction to drugs chemically related to Nabpaclitaxel, Gemcitabine and their excipients;
* Severe cardiac disease (recent myocardial ischemia, severe cardiac arrhythmias, severe cardiac failure);
* Clinical disease progression after first 2 months of systemic Nabpaclitaxel Gemcitabine chemotherapy;
* Any concurrent severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk of associated with study participation or investigational product administration or may interfere with compliance with study procedures or the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into the study;

Primary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: Three and a half years
Secondary outcomes:
measure: The compliance to treatment
timeFrame: Three and a half years
measure: Toxicity assessed by CTCAE
timeFrame: Three and a half years
measure: Postoperative complication assessed by Clavien-Dindo
timeFrame: Three and a half years
measure: Antitumoral activity assessed by PRGS
timeFrame: Three and a half years
measure: Antitumoral activity assessed by PCI
timeFrame: Three and a half years
measure: Antitumoral activity assessed by ascites volume
timeFrame: Three and a half years
measure: Antitumoral activity assessed by tumor markers
timeFrame: Three and a half years
measure: The Progression Free Survival (PFS)
timeFrame: From treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
measure: The Overall Survival (OS)
timeFrame: From treatment start to death, assessed up to 12 months
Other outcomes:
measure: The intravenous area under the curve (AUC) of paclitaxel
timeFrame: Three and a half years
measure: Intra-patient e intra-tumoral heterogeneity
timeFrame: Three and a half years
measure: Identification of pancreatic cancer disease evolution trough pathway analysis a in primary tumor and peritoneal sites during treatments
timeFrame: Three and a half years
Locations:
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study officials:
affiliation: UOS trattamenti integrati della carcinosi peritoneale avanzata -UOC Chirurgia del peritoneo e retroperitoneo - Fondazione Policlinico Universitario A. Gemelli IRCCS
name: Andrea Di Giorgio, MD
role: PRINCIPAL_INVESTIGATOR
References: