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

Phase 2

Recruiting

Conditions: Pancreatic cancer with peritoneal metastases

Registration Number: 2024-518938-81-00

Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief Summary: to evaluate the antitumoral activity of combined Nabpaclitaxel-PIPAC and systemic Nabpaclitaxel-Gemcitabine chemotherapy for pancreatic cancer peritoneal metastases in terms of DCR (ie patients experiencing Complete Response, Partial Response, Stable Disease for ≥ 16 weeks) according to RECIST criteria v. 1.1

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Not specified

Target Recruitment: 38

Inclusion Criteria

Age ≥ 18 years

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

Resolution of all toxic effects of prior therapies or surgical procedures to Grade ≤ 1 (except alopecia and peripheral neuropathy)

In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 x the upper limit of normal (ULN). If the patient has liver metastases, ALT and AST should be < 5 x ULN

Total bilirubin ≤ ULN, or total bilirubin 1.5 x ULN with direct bilirubin ≤ ULN of the laboratory in subjects with documented Gilbert's Syndrome

If screening assessments are abnormal, chemistry assessments may be repeated up to two times; subjects may receive appropriate supplementation prior to re-assessment

Confirmed negative serum pregnancy test (beta-hCG) within 72 hours before starting study treatment for patients with pre- or peri-menopausal status

Male subject must, even if surgically sterilized (ie, status post-vasectomy): Agree to practice highly effective barrier contraception (use condoms) during the entire study treatment period and through 120 days after the last dose of study drugs. For subjects (who have not undergone vasectomy) with female partners of childbearing potential, the subject and his partner must in addition to condoms, use highly effective contraceptive measures when engaging in sexual intercourse throughout the study, and for at least 120 days after the last dose of study drugs (ie oral contraceptive and condoms, intrauterine device).

Willing and able to provide written and informed consent

Histological or cytological proof of pancreatic cancer

Metastatic pancreatic carcinoma with evidence of peritoneal carcinomatosis determined by the treating physician, based on abdominal CT-scan 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

Exclusion Criteria

Advanced metastatic systemic disease with clinical deterioration

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;

Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta-HCG laboratory test

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment and through 120 days after the last dose of study drug. Highly effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the Subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Tubal ligation at least six weeks before taking study treatment. Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject. Combination of the following: Placement of an intrauterine device (IUD) or intrauterine system (IUS); Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository

Patients with extrabdominal 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 Nabpaclitaxel 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

Severe cardiac disease (recent myocardial ischemia, severe arrhythmias, severe cardiac failure)

Known hypersensitivity reaction to drugs chemically related to Nabpaclitaxel, Gemcitabine and their excipients

Clinical disease progression after first 2 months of systemic Nabpaclitaxel Gemcitabine chemotherapy

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The Disease Control Rate (DCR), defined as the combined incidence of complete response (CR), partial response (PR) and stable disease (SD) for ≥ 16 weeks measured during study treatments and at the End of Treatment visit according to the RECIST criteria v. 1.1		The Disease Control Rate (DCR), defined as the combined incidence of complete response (CR), partial response (PR) and stable disease (SD) for ≥ 16 weeks measured during study treatments and at the End of Treatment visit according to the RECIST criteria v. 1.1

Secondary Outcome Measures

Name	Time	Method
The compliance to treatment assessed: - The number of patients unable to undergo six cycles of systemic chemotherapy combined with three PIPAC cycles and reasons for discontinuation - The number of patients who discontinued or postponed beyond 10 days the scheduled standard systemic chemotherapy after each PIPAC cycle. - The number of patients that reduce the dose of systemic chemotherapy during the study; - The number of patients that reduce the dose of PIPAC drug during the study;		The compliance to treatment assessed: - The number of patients unable to undergo six cycles of systemic chemotherapy combined with three PIPAC cycles and reasons for discontinuation - The number of patients who discontinued or postponed beyond 10 days the scheduled standard systemic chemotherapy after each PIPAC cycle. - The number of patients that reduce the dose of systemic chemotherapy during the study; - The number of patients that reduce the dose of PIPAC drug during the study;
The safety and toxicity assessed: - The number of patients with major toxicity, defined as grade ≥3 according to CTCAE v. 5.0, during treatment period and up to 4 weeks after the last combined course; The number of patients with minor toxicity, defined as grade ≤2 according CTCAE v. 5.0 during the treatment period and up to 4 weeks after the last combined course; The number of patients with major and minor postoperative complications, defined as grade ≥3 and grade ≤2 according to Clavien-Dindo,		The safety and toxicity assessed: - The number of patients with major toxicity, defined as grade ≥3 according to CTCAE v. 5.0, during treatment period and up to 4 weeks after the last combined course; The number of patients with minor toxicity, defined as grade ≤2 according CTCAE v. 5.0 during the treatment period and up to 4 weeks after the last combined course; The number of patients with major and minor postoperative complications, defined as grade ≥3 and grade ≤2 according to Clavien-Dindo,
The antitumoral activity of the proposed treatment will be assessed also through: - the pathological tumor response, based on 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 a reduction in the PRGS during subsequent biopsies will be recorded - the modifications of the Peritoneal Cancer Index (PCI) recorded by the surgeon during eac		The antitumoral activity of the proposed treatment will be assessed also through: - the pathological tumor response, based on 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 a reduction in the PRGS during subsequent biopsies will be recorded - the modifications of the Peritoneal Cancer Index (PCI) recorded by the surgeon during eac
The quality of life of the population will be assessed through the potential changes in quality of life scores extracted from the questionnaire QLQ-C30 at different time points		The quality of life of the population will be assessed through the potential changes in quality of life scores extracted from the questionnaire QLQ-C30 at different time points
The Progression Free Survival (PFS), defined as 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 (ie bowel occlusion, inability to oral feeding, refractory ascites), - death;		The Progression Free Survival (PFS), defined as 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 (ie bowel occlusion, inability to oral feeding, refractory ascites), - death;
The Overall Survival (OS), defined as the time between study treatment start and death;		The Overall Survival (OS), defined as the time between study treatment start and death;
Exploratory endpoints - The intravenous area under the curve (AUC) of paclitaxel. The concentration or penetration of paclitaxel in peritoneal samples. The penetration of paclitaxel in peritoneal tissues - Nutritional parameters collected along the study period by blood samples, anthropometric and bio-impedancemetric evaluations, and body composition analysis based on CT scan images		Exploratory endpoints - The intravenous area under the curve (AUC) of paclitaxel. The concentration or penetration of paclitaxel in peritoneal samples. The penetration of paclitaxel in peritoneal tissues - Nutritional parameters collected along the study period by blood samples, anthropometric and bio-impedancemetric evaluations, and body composition analysis based on CT scan images
Translational research endpoints - The germline mutational profile from blood samples - The genomic mutational profile of PM biopsies taken during PIPAC procedures; - The transcriptomic profile of PM biopsies taken during PIPAC procedures; - The tumor cells and tissue microenvironments, including immune system cells; - The circulating cytokines and immune cells profiles.		Translational research endpoints - The germline mutational profile from blood samples - The genomic mutational profile of PM biopsies taken during PIPAC procedures; - The transcriptomic profile of PM biopsies taken during PIPAC procedures; - The tumor cells and tissue microenvironments, including immune system cells; - The circulating cytokines and immune cells profiles.

Trial Locations

Locations (1): Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹
Rome, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Rome, Italy
Andrea Di Giorgio
Site contact
0630157255
andrea.digiorgio@policlinicogemelli.it

Related Trials