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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

9 Mar 2022 → ongoing

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518938-81-00

EudraCT number

2021-002539-51

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacokinetic

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

Secondary objectives 4

1. to evaluate the feasibility, the safety, to further assess the antitumoral activity, to evaluate the overall and progression free survival, and the QoL
2. Exploratory Objectives: to evaluate the pharmacokinetics of Nabpaclitaxel-PIPAC
3. Exploratory Objectives: to evaluate the nutritional status of patients during the study period;
4. Exploratory Objectives: The objective of the translational analysis is to identify and validate biomarkers responsible for response/resistance to Nabpaclitaxel-Gemcitabine and PIPAC treatments

Conditions and MedDRA coding

Pancreatic cancer with peritoneal metastases

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Age ≥ 18 years
2. Willing and able to provide written and informed consent
3. Histological or cytological proof of pancreatic cancer
4. 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
5. Evaluable disease defined by RECIST 1.1 criteria
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
7. Life expectancy of at least 3 months
8. No contraindication for laparoscopy
9. No contraindication for drugs used in the study
10. Adequate bone marrow function: Absolute neutrophil count ≥ 1500 cell./mm3; Platelets ≥ 100000 cell./mm3
11. Hemoglobin ≥ 9 g/dl
12. Adequate renal function (serum creatinine up to 1.5 times the maximal limit of the local laboratory) or else based upon clinical evaluation
13. Resolution of all toxic effects of prior therapies or surgical procedures to Grade ≤ 1 (except alopecia and peripheral neuropathy)
14. 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
15. Total bilirubin ≤ ULN, or total bilirubin 1.5 x ULN with direct bilirubin ≤ ULN of the laboratory in subjects with documented Gilbert's Syndrome
16. If screening assessments are abnormal, chemistry assessments may be repeated up to two times; subjects may receive appropriate supplementation prior to re-assessment
17. Confirmed negative serum pregnancy test (beta-hCG) within 72 hours before starting study treatment for patients with pre- or peri-menopausal status
18. 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 12

1. Advanced metastatic systemic disease with clinical deterioration
2. Patients with extrabdominal tumor spread
3. Patients with a germline or somatic pathogenic variant involving an (Homologous Recombination Repair) HRR-related gene
4. Symptoms of gastrointestinal occlusion and total parenteral nutritional support
5. 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)
6. History of severe and unexpected reactions to Nabpaclitaxel or Gemcitabine
7. Severe cardiac disease (recent myocardial ischemia, severe arrhythmias, severe cardiac failure)
8. Known hypersensitivity reaction to drugs chemically related to Nabpaclitaxel, Gemcitabine and their excipients
9. Clinical disease progression after first 2 months of systemic Nabpaclitaxel Gemcitabine chemotherapy
10. 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;
11. 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
12. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 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 endpoints 8

1. 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;
2. 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,
3. 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
4. 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
5. 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;
6. The Overall Survival (OS), defined as the time between study treatment start and death;
7. 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
8. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Andrea Di Giorgio

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Andrea Di Giorgio

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications