Combined Nabpaclitaxel Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic Nabpaclitaxel-Gemcitabine Chemotherapy for Pancreatic Cancer Peritoneal Metastases

NCT ID: NCT05371223

Last Updated: 2024-02-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2025-07-30

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.

Conditions

Peritoneal Carcinomatosis; Pancreas Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interventional

Eligible patients affected by pancreatic cancer PM will be enrolled according to in-/exclusion criteria.

Each patient will be scheduled for three treatment combined courses for a total of six cycles of endovenous Nabpaclitaxel-Gemcitabine chemotherapy and three of Nabpaclitaxel-PIPAC.

Group Type: EXPERIMENTAL

Combined Nabpaclitaxel Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic Nabpaclitaxel-Gemcitabine

Intervention Type: DRUG

Each combined course is constituted by two consecutive 28-day cycles of systemic chemotherapy (three adminstrations per cycle: days 1,8 and 15) and one cycle of PIPAC administered within 10-13 days from the last administration of systemic chemotherapy. Between each combined course a 7-10 days pause is observed.

The recommended dose of Nabpaclitaxel in combination with Gemcitabine is 125 mg/m2 administered endovenous over 30 minutes on Days 1, 8 and 15 of each 28-day cycle. The concurrent recommended dose of Gemcitabine is 1000 mg/m2 administered intravenously over 30 minutes immediately after the completion of Nabpaclitaxel administration on Days 1, 8 and 15 of each 28-day cycle.

A pressurized aerosol containing Nabpaclitaxel at the dose of 112,5 mg/m2 diluted in a total volume of 200 ml of NaCl 0.9% is applied through the nebulizer inside the abdominal cavity during laparoscopy.

Interventions

Combined Nabpaclitaxel Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic Nabpaclitaxel-Gemcitabine

Each combined course is constituted by two consecutive 28-day cycles of systemic chemotherapy (three adminstrations per cycle: days 1,8 and 15) and one cycle of PIPAC administered within 10-13 days from the last administration of systemic chemotherapy. Between each combined course a 7-10 days pause is observed.

The recommended dose of Nabpaclitaxel in combination with Gemcitabine is 125 mg/m2 administered endovenous over 30 minutes on Days 1, 8 and 15 of each 28-day cycle. The concurrent recommended dose of Gemcitabine is 1000 mg/m2 administered intravenously over 30 minutes immediately after the completion of Nabpaclitaxel administration on Days 1, 8 and 15 of each 28-day cycle.

A pressurized aerosol containing Nabpaclitaxel at the dose of 112,5 mg/m2 diluted in a total volume of 200 ml of NaCl 0.9% is applied through the nebulizer inside the abdominal cavity during laparoscopy.

Intervention Type: DRUG

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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrea Di Giorgio, MD

Role: PRINCIPAL_INVESTIGATOR

UOS trattamenti integrati della carcinosi peritoneale avanzata -UOC Chirurgia del peritoneo e retroperitoneo - Fondazione Policlinico Universitario A. Gemelli IRCCS

Locations

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Andrea Di Giorgio, MD

Role: CONTACT

andrea.digiorgio@policlinicogemelli.it

+393288994872

Facility Contacts

Andrea Di Giorgio, MD

Role: primary

andrea.digiorgio@policlinicogemelli.it

+390630157255

References

Di Giorgio A, Ferracci F, Bagala C, Carbone C, Salvatore L, Strippoli A, Attalla El Halabieh M, Abatini C, Alfieri S, Pacelli F, Tortora G. Combined Nabpaclitaxel pressurized intraPeritoneal aerosol chemotherapy with systemic Nabpaclitaxel-Gemcitabine chemotherapy for pancreatic cancer peritoneal metastases: protocol of single-arm, open-label, phase II trial (Nab-PIPAC trial). Pleura Peritoneum. 2024 Nov 6;9(3):121-129. doi: 10.1515/pp-2024-0010. eCollection 2024 Sep.

Reference Type: DERIVED

PMID: 39544430 (View on PubMed)

Other Identifiers

4368

Identifier Type: -

Identifier Source: org_study_id