Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) and Electrostatic PIPAC (ePIPAC) With Paclitaxel In Patients With Peritoneal Carcinomatosis
NCT ID: NCT05395910
Last Updated: 2024-05-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1
36 participants
INTERVENTIONAL
2023-08-04
2025-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Gastric Carcinomatosis. Phase II Randomized Study
NCT04065139
Oncological Benefits of Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients With T3-4 Gastric Cancer Cyt-
NCT04595929
Intraperitoneal Aerosol Chemotherapy in Gastric Cancer
NCT01854255
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Using Paclitaxel in Gastric Cancer Patients With Peritoneal Metastasis
NCT04913662
Effect of the PIPAC on the Survival Rate of Patients With Peritoneal Carcinomatosis of Gastric Origin
NCT04879953
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery technique for PC taking advantage of physical laws (gaseous nature, hydrostatic pressure) with superior pharmacological properties (homogeneous distribution, deeper tissue penetration). It is applied through laparoscopy and is minimally invasive. Adding electrostatic loading (ePIPAC) as an adjunct would further improve the pharmacological properties of PIPAC since it should induce precipitation of the aerosolized drug, increasing the ratio between the dose applied and the dose in the target tissue.
Systemic toxicity is significantly reduced due to the peritoneum/blood barrier and the low dose applied (about 20% of the usual systemic dose). A systematic review highlighted that PIPAC combines the benefits of a minimally invasive approach with pharmacokinetic advantages of intraperitoneal administration and pressurized vaporization. It concluded that PIPAC is feasible, safe, and warrants further prospective studies. PIPAC may be combined with systemic palliative chemotherapy with minimal additional organ toxicity. This method of treatment avoids the morbidity and mortality of HIPEC. PIPAC has been shown in pre-clinical studies to be potentially more efficacious than catheter-based IP-chemotherapy due to better drug distribution and penetration. In clinical use, PIPAC can be repeated at intervals of 6 weeks to 3 months. This allows repeated objective assessment of therapy effect over time.
To date, PIPAC has only been utilized to administer Oxaliplatin or a combination of Doxorubicin/Cisplatin. Paclitaxel is an approved drug for systemic chemotherapy for several cancers, and also has well-documented intraperitoneal use for ovarian cancer and gastric cancer. It is a hydrophobic, high molecular weight compound resulting in low absorption through the lymphatic system after IP administration with a much higher peritoneal to plasma peak concentration and AUC ratios (\>1000 versus 25 and \>1000 versus 16 respectively). As such, IP Paclitaxel may be potentially more efficacious with less systemic toxicity than IP Oxaliplatin. However, no clinical data exists in the published literature for PIPAC/ePIPAC paclitaxel.
This proposed prospective study is the first clinical study 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 PC. Peritoneal biopsies will be collected prior to and after PIPAC/ePIPAC to assess tissue drug concentration and depth of drug penetration. Collection of biospecimens including peritoneal tissue, peritoneal fluid and blood will be used for correlative studies including paclitaxel resistance analysis and development of cancer modelling platforms. For the individual patient, repeated biopsies and molecular profiling may also facilitate individualized therapy. For medical research, PIPAC/ePIPAC may deliver measurable progress in 3-5 years because the assessment interval is short (6 weeks) in this disease with rapid progression (6-12 months to death).
This study will determine the safety dose range of PIPAC/ePIPAC paclitaxel. This will allow us to design a phase II trial to evaluate clinical efficacy. On a larger scale, the success of this PIPAC/ePIPAC trial would add a valuable treatment option to our arsenal in the treatment of PC.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
PIPAC Paclitaxel
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.
Paclitaxel
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.
ePIPAC Paclitaxel
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.
Paclitaxel
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Paclitaxel
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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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.
Exclusion Criteria
* 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
21 Years
99 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National University Hospital, Singapore
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Bok Yan Jimmy So, MBChB
Role: PRINCIPAL_INVESTIGATOR
National University Hospital, Singapore
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
National University Hospital
Singapore, , Singapore
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
DSRB 2020/01447
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.