GEMCITABINE for Pancreatic cancer with peritoneal metastases

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- Willing and able to provide written and informed consent"}
• {"criterion_text":"- Histological or cytological proof of pancreatic cancer"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Evaluable disease defined by RECIST 1.1 criteria"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1"}
• {"criterion_text":"- Life expectancy of at least 3 months"}
• {"criterion_text":"- No contraindication for laparoscopy"}
• {"criterion_text":"- No contraindication for drugs used in the study"}
• {"criterion_text":"- Adequate bone marrow function: Absolute neutrophil count ≥ 1500 cell./mm3; Platelets ≥ 100000 cell./mm3"}
• {"criterion_text":"- Hemoglobin ≥ 9 g/dl"}
• {"criterion_text":"- Adequate renal function (serum creatinine up to 1.5 times the maximal limit of the local laboratory) or else based upon clinical evaluation"}
• {"criterion_text":"- Resolution of all toxic effects of prior therapies or surgical procedures to Grade ≤ 1 (except alopecia and peripheral neuropathy)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Total bilirubin ≤ ULN, or total bilirubin 1.5 x ULN with direct bilirubin ≤ ULN of the laboratory in subjects with documented Gilbert's Syndrome"}
• {"criterion_text":"- If screening assessments are abnormal, chemistry assessments may be repeated up to two times; subjects may receive appropriate supplementation prior to re-assessment"}
• {"criterion_text":"- Confirmed negative serum pregnancy test (beta-hCG) within 72 hours before starting study treatment for patients with pre- or peri-menopausal status"}
• {"criterion_text":"- 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)."}

Exclusion criteria

• {"criterion_text":"- Advanced metastatic systemic disease with clinical deterioration"}
• {"criterion_text":"- Patients with extrabdominal tumor spread"}
• {"criterion_text":"- Patients with a germline or somatic pathogenic variant involving an (Homologous Recombination Repair) HRR-related gene"}
• {"criterion_text":"- Symptoms of gastrointestinal occlusion and total parenteral nutritional support"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- History of severe and unexpected reactions to Nabpaclitaxel or Gemcitabine"}
• {"criterion_text":"- Severe cardiac disease (recent myocardial ischemia, severe arrhythmias, severe cardiac failure)"}
• {"criterion_text":"- Known hypersensitivity reaction to drugs chemically related to Nabpaclitaxel, Gemcitabine and their excipients"}
• {"criterion_text":"- Clinical disease progression after first 2 months of systemic Nabpaclitaxel Gemcitabine chemotherapy"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"DCR defined as combined incidence of CR, PR and SD for ≥16 weeks measured during study treatments and at the End of Treatment visit according to RECIST v.1.1"}

Secondary endpoints

• {"endpoint_text":"- The compliance to treatment assessed: -\t The number of patients unable to undergo six cycles of systemic chemotherapy combined with three PIPAC cycles and reasons for discontinuation -\tThe number of patients who discontinued or postponed beyond 10 days the scheduled standard systemic chemotherapy after each PIPAC cycle. -\tThe number of patients that reduce the dose of systemic chemotherapy during the study; -\tThe number of patients that reduce the dose of PIPAC drug during the study;","definition_or_measurement_approach":"Assessed by counts of patients unable to complete planned systemic and PIPAC cycles, reasons for discontinuation, number who discontinue/postpone >10 days, and number who reduce doses"}
• {"endpoint_text":"- 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,","definition_or_measurement_approach":"Safety/toxicity measured by CTCAE v5.0 grades for major (≥3) and minor (≤2) events during treatment and up to 4 weeks post-treatment; postoperative complications graded by Clavien-Dindo"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Pathological tumor response by PRGS on peritoneal biopsies (blinded pathologist); changes in Peritoneal Cancer Index (PCI) recorded intraoperatively"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"QoL measured by changes in EORTC QLQ-C30 scores at predefined time points"}
• {"endpoint_text":"- 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;","definition_or_measurement_approach":"PFS measured as time from treatment start to radiologic progression per RECIST v1.1, clinical progression (e.g., bowel occlusion, inability to feed, refractory ascites), or death"}
• {"endpoint_text":"- The Overall Survival (OS), defined as the time between study treatment start and death;","definition_or_measurement_approach":"OS measured as time from study treatment start to death"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Pharmacokinetic measures of paclitaxel AUC and tissue penetration; nutritional parameters via blood tests, anthropometry, bioimpedance, and CT-based body composition"}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Molecular profiling of germline and tumor (genomic, transcriptomic), tumor microenvironment characterization, and circulating cytokine/immune cell profiling from blood and biopsy samples"}

Italy

Earliest CTIS Part Ii Submission Date

11-10-2024

Latest Decision Or Authorization Date

02-12-2024

Processing Time Days

52

Number Of Sites

1

Number Of Participants

38

Primary sponsor

Full Name

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy