Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) With Oxaliplatin In Patients With Peritoneal Carcinomatosis

NCT03172416 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: DSRB 2016/01088
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 3

Brief Summary

PIPAC is a procedure that involves the administration of intraperitoneal chemotherapy using an innovative concept that enhances the efficacy by taking advantage of the physical properties of gas and pressure. The chemotherapy drugs will be delivered in aerosolised form. This results in a superior distribution and depth of penetration of the drug. This research study serves to determine the safety profile and tolerability of PIPAC with oxaliplatin. It may offer a novel and effective option of treatment for patients with peritoneal carcinomatosis, who, at present have limited options involving the use of systemic chemotherapy and who suffer from poor life expectancy and poor quality of life. To date, most trials have used PIPAC cisplatin with doxorubicin, or oxaliplatin alone, and more studies are on-going globally. Intravenous (IV) nivolumab has been approved for the treatment of progressive gastric cancer after conventional chemotherapy. PIPAC in combination with nivolumab may have the potential to improve immune activation and response to immune checkpoint inhibition for patients with peritoneal disease. Hence we propose an amendment to our trial protocol for the addition of a second cohort (Cohort 2) to investigate the safety and tolerability of the combination of PIPAC oxaliplatin and IV nivolumab.

Conditions

Peritoneal Carcinomatosis

Keywords

Gastric Cancer; Unresectable Peritoneal Carcinomatosis; Oxaliplatin; Pressurized intraperitoneal aerosol chemotherapy; Nivolumab

Outcome Measures

Primary Outcomes (4)

• Safety Profile of PIPAC with oxaliplatin by monitoring adverse event profile of patient undergo PIPAC

  1 to 2 years

• Tolerability of PIPAC with oxaliplatin by monitoring dose limiting toxicities

  1-2 years

• Safety Profile of PIPAC with oxaliplatin in combination with IV nivolumab by monitoring adverse event profile of patient undergo PIPAC

  1-2 years

• Tolerability of PIPAC with oxaliplatin in combination with IV nivolumab by monitoring dose limiting toxicities

  1-2 years

Secondary Outcomes (10)

• Clinical response of PIPAC with oxaliplatin according to Peritoneal Cancer Index (PCI)

  1-2 years

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

  1-2 years

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

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

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

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

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

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

Study Arms (1)

Oxaliplatin

OTHER

3+3 dose escalation of oxaliplatin This is a single arm phase I trial in a 3 + 3 dose escalation and cohort expansion design evaluating the safety and tolerability of PIPAC using oxaliplatin. The pre-planned dose levels of oxaliplatin are 45mg/m2 (Cohort 1), 60mg/m2 (Cohort 2), 90mg/m2 (Cohort 3),120mg/m2 (Cohort 4) and 150mg/m2 (Cohort 5) administered as PIPAC. Successive cohorts of patients (3 participants/cohort) will be enrolled and started on a fixed dose of oxaliplatin. The protocol specifies oxaliplatin 45mg/m2 once every 6 weeks for Cohort 1. Dose escalation continues until dose-limiting toxicities (DLT) are observed in one-third of participants. If no DLT occurs, the next cohort will be enrolled at the next planned dose level. If 1 DLT occurs in a cohort, another 3 patients will be treated with the same dose level. Oxaliplatin every 6 weeks with IV nivolumab every 2 weeks PIPAC oxaliplatin at 90mg/m2 every 6 weeks with IV nivolumab at 240mg every 2 weeks

Drug: Oxaliplatin; Drug: Oxaliplatin & Nivolumab

Interventions

Oxaliplatin DRUG

This study started as a prospective, single arm phase I trial in a 3 + 3 dose escalation evaluating the safety and tolerability of PIPAC using oxaliplatin in patients with peritoneal carcinomatosis.

Oxaliplatin

Oxaliplatin & Nivolumab DRUG

PIPAC oxaliplatin 90mg/m2 has been well tolerated in our Cohort 1 study. Hence, we added a second cohort (Cohort 2) which combines PIPAC oxaliplatin at 90mg/m2 every 6 weeks with IV nivolumab at 240mg every 2 weeks to evaluate the safety and tolerability of combination therapy.

Oxaliplatin

Eligibility Criteria

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

You may qualify if:

• Gastric 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 (or whichever is longer) prior to PIPAC.
• Age \>21 years.
• Eastern Cooperative Oncology Group performance status 0-1.
• Adequate bone marrow function (neutrophil count \>1500/mm3, hemoglobin \>8.0 g/dl and platelet count \>100 000/mm3).
• Adequate liver function (bilirubin, AST/ALT within upper limit of normal)
• Adequate renal function (serum creatinine within the upper limit of normal)
• Expected survival \>3 months
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

You may not qualify if:

• Predominant extra-peritoneal metastases at the discretion of the study team after discussion at the multidisciplinary tumour board
• Good response to systemic chemotherapy based on RECIST guidelines VI.I with complete or partial response to systemic chemotherapy.
• Known allergy to oxaliplatin
• Previous malignancy unrelated to current peritoneal carcinomatosis diagnosed in the last 5 years
• Patients with treated skin cancer besides melanoma may be included.
• 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
• Gastric cancer patients with peritoneal metastasis on peritoneal cytology/histology, for whom oxaliplatin is considered standard of care for the peritoneal carcinoma of origin.
• 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 (or whichever is longer) prior to PIPAC
• 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 0-1

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (3)

Ghent University Hospital

Ghent, 9000, Belgium

Location

National University Hospital

Singapore, 119228, Singapore

Location

National Cancer Centre Singapore

Singapore, Singapore

Location

Related Publications (8)

• 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

• 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

• Robella M, Vaira M, De Simone M. Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis. World J Surg Oncol. 2016 Apr 29;14:128. doi: 10.1186/s12957-016-0892-7.

  PMID: 27125996 BACKGROUND

• Solass W, Kerb R, Murdter T, Giger-Pabst U, Strumberg D, Tempfer C, Zieren J, Schwab M, Reymond MA. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol. 2014 Feb;21(2):553-9. doi: 10.1245/s10434-013-3213-1. Epub 2013 Sep 5.

  PMID: 24006094 BACKGROUND

• Demtroder C, Solass W, Zieren J, Strumberg D, Giger-Pabst U, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin in colorectal peritoneal metastasis. Colorectal Dis. 2016 Apr;18(4):364-71. doi: 10.1111/codi.13130.

  PMID: 26400556 BACKGROUND

• Sundar R, Chia DKA, Zhao JJ, Lee ARYB, Kim G, Tan HL, Pang A, Shabbir A, Willaert W, Ma H, Huang KK, Hagihara T, Tan ALK, Ong CJ, Wong JSM, Seo CJ, Walsh R, Chan G, Cheo SW, Soh CCC, Callebout E, Geboes K, Ng MCH, Lum JHY, Leow WQ, Selvarajan S, Hoorens A, Ang WH, Pang H, Tan P, Yong WP, Chia CSL, Ceelen W, So JBY. Phase I PIANO trial-PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes. ESMO Open. 2024 Sep;9(9):103681. doi: 10.1016/j.esmoop.2024.103681. Epub 2024 Sep 16.

  PMID: 39288528 DERIVED

• Kim G, Tan HL, Chen E, Teo SC, Jang CJM, Ho J, Ang Y, Ngoi NYL, Chee CE, Lieske B, Shabbir A, Wang LZ, So JBY, Yong WP. Study protocol: phase 1 dose escalating study of Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) with oxaliplatin in peritoneal metastasis. Pleura Peritoneum. 2018 Aug 29;3(3):20180118. doi: 10.1515/pp-2018-0118. eCollection 2018 Sep 1.

  PMID: 30911663 DERIVED

MeSH Terms

Conditions

Peritoneal Neoplasms; Stomach Neoplasms

Interventions

Oxaliplatin; Nivolumab

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jimmy So, MBChB

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2017
• First Posted: June 1, 2017
• Study Start: April 12, 2017
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); SG (2)