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

Prior treatment

• 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 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)

Other illness

• Advanced metastatic systemic disease with clinical deterioration
• 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

Lab values

• 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

Other

• 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

• 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