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

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National University Hospital, Singapore
• Treatments: Nivolumab; Oxaliplatin

Criteria

Inclusion Criteria for Cohort 1:

• 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.

Exclusion Criteria for Cohort 1:

• 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

Inclusion Criteria for Cohort 2:

• 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

• 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

• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

Exclusion Criteria for Cohort 2:

• Predominant extra-peritoneal metastases at the discretion of the study team after discussion at the multidisciplinary tumour board

• Patients who have previously received prior nivolumab or PD-/L1 blockade therapy

• Good response to systemic chemotherapy based on RECIST guidelines VI.I with complete or partial response to systemic chemotherapy.

• Active autoimmune disease requiring disease-modifying therapy.

• Concurrent systemic steroid therapy higher than physiologic dose (equivalent of prednisolone 10mg daily), except for short courses (< 2 weeks) required to treat acute medical conditions (e.g. asthma exacerbation, or for CT scans)

• Any form of active primary or secondary immunodeficiency.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension (systolic >160 mmHg and/or diastolic >100 mmHg), symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction/cerebrovascular event (≤ 6 months prior to study entry), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, long term systemic immunosuppressant or corticosteroid, and active viral hepatitis.

• Known allergy to oxaliplatin

• Previous malignancy unrelated to current peritoneal carcinomatosis diagnosed in the last 2 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