Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) and Electrostatic PIPAC (ePIPAC) With Paclitaxel In Patients With Peritoneal Carcinomatosis

NCT05395910 | Recruiting Phase 1 DMC

• 1 other identifier: DSRB 2020/01447
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Peritoneal carcinomatosis (PC) is a miserable disease with poor treatment outcome. Intraperitoneal administration of anticancer drugs enables an extremely high concentration of drugs to directly contact the target cancer lesions in the peritoneal cavity. However, its effectiveness is limited by the intraperitoneal distribution and penetration of the drug. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative intraperitoneal chemotherapy concept that enhances efficacy by taking advantage of the physical properties of gas and pressure. Electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (ePIPAC) may further enhance these benefits. This research study serves to determine the safety profile and tolerability of PIPAC/ePIPAC with paclitaxel. It will determine the maximal tolerated dose (MTD) and evaluate the safety and tolerability, and pharmacokinetics of PIPAC/ePIPAC paclitaxel in pre-treated patients with peritoneal carcinomatosis (PC). It may offer a novel and effective option of treatment for patients with PC, who, at present have limited options involving the use of systemic chemotherapy and who suffer from poor life expectancy and poor quality of life.

Conditions

Peritoneal Carcinomatosis

Keywords

Gastric Cancer; Oesophageal Cancer; Bilio-pancreatic tract Cancer; Gynaecological Cancer; Colorectal Cancers; Unresectable Peritoneal Carcinomatosis; Pressurized intraperitoneal aerosol chemotherapy; Electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy; Paclitaxel

Outcome Measures

Primary Outcomes (2)

• Tolerability of PIPAC /ePIPAC with Paclitaxel by monitoring dose limiting toxicities

  Dose limiting toxicities are monitored to evaluate the tolerability of PIPAC /ePIPAC

  1 - 2 years

• Safety Profile of PIPAC/ePIPAC with Paclitaxel by monitoring adverse events

  Adverse events are monitored to evaluate the safety profile of PIPAC/ePIPAC

  1 - 2 years

Secondary Outcomes (5)

• Clinical response of PIPAC/ePIPAC with Paclitaxel according to Peritoneal Cancer Index (PCI)

  1 - 2 years

• Pathological response of PIPAC/ePIPAC with Paclitaxel according to Peritoneal Regression Grade Scoring (PRGS) System

  1 - 2 years

• Maximum concentration (Cmax) of Paclitaxel administered via PIPAC/ePIPAC using blood drawn from patient.

  Pre-dose; 30 and 45 minutes; and 1, 2, 4, 8, 24, 30, 48 hour

• Half-life (t1/2) of Paclitaxel administered via PIPAC/ePIPAC using blood drawn from patient

  Pre-dose; 30 and 45 minutes; and 1, 2, 4, 8, 24, 30, 48 hour

• Area under the curve (AUC) of Paclitaxel administered via PIPAC/ePIPAC using blood drawn from patient.

  Pre-dose; 30 and 45 minutes; and 1, 2, 4, 8, 24, 30, 48 hour

Study Arms (2)

PIPAC Paclitaxel

EXPERIMENTAL

3 patients will be allocated to PIPAC arm at Paclitaxel 15mg/m2. If there is 1 dose limiting toxicity (DLT), an additional 3 patients will be allocated to PIPAC arm at 15mg/m2. If there is 2 - 3 DLT, study had exceeded its Maximum Tolerable Dose (MTD) and we will proceed to stop recruitment. Should there be no DLT, recruitment at PIPAC 30mg/m2 and ePIPAC 15mg/m2 will occurs concurrently in an alternating fashion. PIPAC/ePIPAC dose escalation will continue until a MTD has been reached. Should there be no DLT at PIPAC 30mg/m2 and ePIPAC 15mg/m2, recruitment at PIPAC 45mg/m2 and ePIPAC 30mg/m2 will occurs concurrently in an alternating fashion. Finally, should there be no DLT, recruitment at ePIPAC 45mg/m2 will occurs.

Drug: Paclitaxel

ePIPAC Paclitaxel

EXPERIMENTAL

Should there be no DLT under PIPAC arm at Paclitaxel 15mg/m2, recruitment at ePIPAC 15mg/m2 and PIPAC 30mg/m2 will occurs concurrently in an alternating fashion. PIPAC/ePIPAC dose escalation will continue until a MTD has been reached. Should there be no DLT at PIPAC 30mg/m2 and ePIPAC 15mg/m2, recruitment at PIPAC 45mg/m2 and ePIPAC 30mg/m2 will occurs concurrently in an alternating fashion. Finally, should there be no DLT, recruitment at ePIPAC 45mg/m2 will occurs.

Drug: Paclitaxel

Interventions

Paclitaxel DRUG

This is a prospective, two armed phase I trial in a 3 + 3 dose escalation evaluating the safety and tolerability of PIPAC/ePIPAC using paclitaxel in patients with peritoneal carcinomatosis.

PIPAC Paclitaxel; ePIPAC Paclitaxel

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All solid cancer patients with peritoneal metastasis on peritoneal cytology/histology.
• Patients who refuse, are unable to tolerate, or have completed at least 1st line systemic chemotherapy
• Patients who have completed chemotherapy/targeted therapy \> 21 days or at least 5 half-lives (whichever is longer) prior to PIPAC/ePIPAC
• Patients must have recovered (≤ grade 1) from all reversible treatment toxicity from prior chemotherapy, radiotherapy or surgery.
• Age ≥21 years
• Eastern Cooperative Oncology Group performance status 0-2
• Adequate bone marrow function (neutrophil count ≥1500/mm3, hemoglobin ≥8.0 g/dl and platelet count ≥100 000/mm3)
• Adequate liver function (bilirubin ≤ 1.5x ULN (upper limit normal) and AST/ALT ≤3x ULN or ≤5x ULN in the presence of liver metastases)
• Adequate renal function (serum creatinine ≤1.5x ULN)
• Expected survival \>3 months
• Able to understand and the willingness to sign a written informed consent document
• The effects of proposed regimen on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because antitumor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Patients with treated skin cancer besides melanoma may be included.

You may not qualify if:

• Predominant extra-peritoneal metastases at the discretion of the study team after discussion at the multidisciplinary tumor board
• Patients with clinical or radiological evidence of hollow viscera perforation or impending perforation, including but not limited to gastric, small bowel, colon, gallbladder. Decision will be made at the discretion of the study team in consultation with multidisciplinary tumour board or with necessary specialists
• Good response to systemic chemotherapy based on RECIST guidelines version 1.1 with complete or partial response to systemic chemotherapy
• Known allergy to paclitaxel
• Previous malignancy unrelated to current peritoneal carcinomatosis diagnosed in the last 2 years
• Patients with reproductive potential who refuse to use an adequate means of contraception (including male patients)
• Significant disease or conditions which, in the investigator's opinion, would exclude patient from the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or lactating female
• Patients with bowel obstruction, total dependence on parenteral nutrition, or who are undergoing gastrointestinal resection in the same setting

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, 119228, Singapore

RECRUITING

Related Publications (10)

• Ishigami H, Kitayama J, Kaisaki S, Hidemura A, Kato M, Otani K, Kamei T, Soma D, Miyato H, Yamashita H, Nagawa H. Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis. Ann Oncol. 2010 Jan;21(1):67-70. doi: 10.1093/annonc/mdp260. Epub 2009 Jul 15.

  PMID: 19605503 BACKGROUND

• Kobayashi D, Kodera Y. Intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis. Gastric Cancer. 2017 Mar;20(Suppl 1):111-121. doi: 10.1007/s10120-016-0662-9. Epub 2016 Nov 1.

  PMID: 27803990 BACKGROUND

• Solass W, Hetzel A, Nadiradze G, Sagynaliev E, Reymond MA. Description of a novel approach for intraperitoneal drug delivery and the related device. Surg Endosc. 2012 Jul;26(7):1849-55. doi: 10.1007/s00464-012-2148-0. Epub 2012 May 12.

  PMID: 22580869 BACKGROUND

• Solass W, Herbette A, Schwarz T, Hetzel A, Sun JS, Dutreix M, Reymond MA. Therapeutic approach of human peritoneal carcinomatosis with Dbait in combination with capnoperitoneum: proof of concept. Surg Endosc. 2012 Mar;26(3):847-52. doi: 10.1007/s00464-011-1964-y. Epub 2011 Nov 1.

  PMID: 22042585 BACKGROUND

• Grass F, Vuagniaux A, Teixeira-Farinha H, Lehmann K, Demartines N, Hubner M. Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis. Br J Surg. 2017 May;104(6):669-678. doi: 10.1002/bjs.10521.

  PMID: 28407227 BACKGROUND

• Reymond M, Demtroeder C, Solass W, Winnekendonk G, Tempfer C. Electrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC): first in-human application. Pleura Peritoneum. 2016 Jun 1;1(2):109-116. doi: 10.1515/pp-2016-0005. Epub 2016 Apr 29.

  PMID: 30911614 BACKGROUND

• Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III Trial Comparing Intraperitoneal and Intravenous Paclitaxel Plus S-1 Versus Cisplatin Plus S-1 in Patients With Gastric Cancer With Peritoneal Metastasis: PHOENIX-GC Trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. doi: 10.1200/JCO.2018.77.8613. Epub 2018 May 10.

  PMID: 29746229 BACKGROUND

• Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. doi: 10.1056/NEJMoa052985.

  PMID: 16394300 BACKGROUND

• Chan DY, Syn NL, Yap R, Phua JN, Soh TI, Chee CE, Nga ME, Shabbir A, So JB, Yong WP. Conversion Surgery Post-Intraperitoneal Paclitaxel and Systemic Chemotherapy for Gastric Cancer Carcinomatosis Peritonei. Are We Ready? J Gastrointest Surg. 2017 Mar;21(3):425-433. doi: 10.1007/s11605-016-3336-3. Epub 2016 Dec 15.

  PMID: 27981493 BACKGROUND

• Kono K, Yong WP, Okayama H, Shabbir A, Momma T, Ohki S, Takenoshita S, So J. Intraperitoneal chemotherapy for gastric cancer with peritoneal disease: experience from Singapore and Japan. Gastric Cancer. 2017 Mar;20(Suppl 1):122-127. doi: 10.1007/s10120-016-0660-y. Epub 2016 Oct 20.

  PMID: 27766496 BACKGROUND

MeSH Terms

Conditions

Peritoneal Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Colorectal Neoplasms

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Bok Yan Jimmy So, MBChB

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bok Yan Jimmy So, MBChB

CONTACT

+65 6772 5555; sursbyj@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2022
• First Posted: May 27, 2022
• Study Start: August 4, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)