A Phase 2 interventional study of Combined Nabpaclitaxel Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic Nabpaclitaxel-Gemcitabine in Peritoneal Carcinomatosis and Pancreas Neoplasm, sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-02-26.
Sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Phase 2, Interventional, and Treatment
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.
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.
3,235 studies on the registry are indexed under Pancreatic Neoplasms; 899 are open to participants now.
This study's planned enrollment of 38 is below the median of 46 across 2,424 interventional studies indexed under Pancreatic Neoplasms.
Browse Pancreatic Neoplasms studies →Fondazione Policlinico Universitario Agostino Gemelli IRCCS is the lead sponsor of 920 studies on the registry; 529 are open to participants now.
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Exclusion Criteria:
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.
Drug: 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.
Disease Control Rate (DCR)
The Disease Control Rate (DCR) defined as the combined incidence of complete response (CR), partial response (PR) and stable disease (SD) according to the RECIST v. 1.1 criteria during study treatments and the EOT visit.
Time frame: Three and a half years
The compliance to treatment
- The number of patients unable to undergo six cycles of systemic chemotherapy combined with three PIPAC cycles and reasons for discontinuation.
Time frame: Three and a half years
Toxicity assessed by CTCAE
* The number of patients with major toxicity, defined as grade ≥3 according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0 during the on-study evaluation phase and up to 4 weeks after the last chemotherapy administration. * The number of patients with minor toxicity, defined as grade ≤2 according to CTCAE v5.0 during the treatment period and up to 4 weeks after the last chemotherapy administration.
Time frame: Three and a half years
Postoperative complication assessed by Clavien-Dindo
-The number of patients with major and minor postoperative complications, defined as grade ≥3 and grade ≤2 according to Clavien-Dindo, respectively, during the treatment period and up to 4 weeks after the last PIPAC procedure.
Time frame: Three and a half years
Antitumoral activity assessed by PRGS
-The pathological tumor response, based on the review of peritoneal biopsies collected during each PIPAC, performed by a pathologist blinded to clinical outcomes using the Peritoneal Regression Grading Score (PRGS). A patient will be considered a responder if any reduction in the PRGS during subsequent biopsies will be recorded; (PRGS 1: Complete regression without cancer cells - PRGS 2: higher response with prevalence of regressive phenomena and only a few residual cancer cells - PRGS 3: minor response with prevalence of residual cancer cells and poor regressive phenomena - PRGS 4: no response to therapy without regressive phenomena A reduction in the PRGS during subsequent biopsies will be considered as a positive response.)
Time frame: Three and a half years
Antitumoral activity assessed by PCI
-The macroscopic tumor response, based on Peritoneal Cancer Index (PCI) recorded during each PIPAC; The PCI index will be calculated according to the Sugarbaker method, which provides the assignment of a score between 0 and 3 based on the size of peritoneal metastases (0 without lesions; 1 if diam. 0.5 cm; 2 if diam. between 0.5 and 5 cm; 3 if diam \> 5 cm or coalescent lesions) observed in 12 regions of the peritoneal cavity. The maximum score is 39.
Time frame: Three and a half years
Antitumoral activity assessed by ascites volume
- The macroscopic tumor response, based on ascites volume recorded during each PIPAC
Time frame: Three and a half years
Antitumoral activity assessed by tumor markers
- The biochemical tumor response, based on tumor markers (CEA, Ca 19.9, Ca 125) measured at different time points.
Time frame: Three and a half years
The Progression Free Survival (PFS)
the time between treatment start and one of the following events, whichever comes first: * radiologic progression based on RECIST criteria v. 1.1, * clinical progression (eg, bowel occlusion, inability to oral feeding, refractory ascites), * death;
Time frame: 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
The Overall Survival (OS)
The Overall Survival (OS) is defined as the time between treatment start and death.
Time frame: From treatment start to death, assessed up to 12 months
The intravenous area under the curve (AUC) of paclitaxel
The concentration of paclitaxel in peritoneal samples. The penetration of paclitaxel in peritoneal tissues.
Time frame: Three and a half years
Intra-patient e intra-tumoral heterogeneity
- The germline mutational profile from blood samples
Time frame: Three and a half years
Identification of pancreatic cancer disease evolution trough pathway analysis a in primary tumor and peritoneal sites during treatments
- The genomic mutational profile of PM biopsies taken during PIPAC;
Time frame: Three and a half years
Plan to share: No
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Fondazione Policlinico Universitario Agostino Gemelli IRCCS