Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Neoplasm Metastasis

Stomach Neoplasms

Pancreatic Neoplasms

Cholangiocarcinoma

Colorectal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Carcinoma

Bile Duct Neoplasms

Peritoneal Neoplasms

Appendiceal Neoplasms

Intestinal Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Biliary Tract Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Abdominal Neoplasms

Peritoneal Diseases

Cecal Neoplasms

Cecal Diseases

Stomach Cancer

Pancreatic Cancer

Bile Duct Cancer

Small Intestine Cancer

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

PIPAC with Onivyde (30 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

PIPAC with Onivyde (45 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

PIPAC with Onivyde (60 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

PIPAC with Onivyde (75 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

PIPAC with Onivyde (90 mg/m²) will be administered every 4 to 6 weeks for 3 cycles.

Nanoliposomal irinotecan (Nal-IRI, Onivyde) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 30 to 90 mg/m². PIPAC will be performed every 4 to 6 weeks for 3 cycles.

PIPAC with Nal-IRI

Wim P Ceelen, MD, PhD, Prof

Wouter Willaert, MD, PhD, Prof

The PIPAC NAL-IRI study is designed to examine the maximal tolerated dose of nanoliposomal irinotecan (Nal-IRI, Onivyde) administered with repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC), in a monocentric, phase I trial.

Peritoneal metastases (PM) are a common manifestation of gastrointestinal cancer. The prognosis of patients with PM is particularly poor, and response to systemic chemotherapy is worse compared to parenchymal metastatic cancer in the liver or lungs. In addition, patients with PM frequently develop debilitating symptoms such as intractable ascites, bowel obstruction, or ureteric obstruction, resulting in a severely compromised quality of life.

In selected patients with widespread PM, pressurized intraperitoneal aerosol chemotherapy (PIPAC) holds considerable promise. Briefly, PIPAC combines laparoscopy with intraperitoneal (IP) administration of chemotherapy as an aerosol, which is generated by a nebulizer. The pharmacokinetic (PK) and clinical advantages of PIPAC may be further enhanced by using nanosized anticancer drugs. Nal-IRI (Onivyde) is a nanoliposomal formulation of irinotecan (Camptothecin-11 (CPT-11)), with a markedly superior efficacy when compared with free CPT-11 in human breast and colon cancer xenograft models.

This is a phase I clinical study with aerosolized IP Nal-IRI in patients with PM from GI cancer. In this phase I study, dose escalation will be combined with pharmacokinetic/pharmacodynamic modelling which incorporates, in addition to plasma, tumour tissue, and peritoneal drug concentrations, biomarkers of toxicity and efficacy.

Phase I study with dose escalation according to two-stage time-to-event continual reassessment method (TITE-CRM): 3x30 - 3x45 - 4x60 - 4x 75 - 16x90 mg/m2 (number of patients x assigned dose). Dose escalation is continued until dose-limiting toxicity (DLT) is observed. Only DLTs that take place within 14 weeks of the start of the treatment are considered.

From that moment, TITE-CRM updates an initial prior estimate of the probabilities of DLT based on all available information, including patients with incomplete follow-up. Newly accrued patients are assigned the dose whose estimated probability of DLT at that time is closest to target probability. This method allows for continuous, staggered accrual of patients. The target-probability of DLT is 30%. The estimated MTD will be the dose whose estimated posterior probability of DLT is closest to that targeted probability.

Intraperitoneal Aerosolized Nanoliposomal Irinotecan (Nal-IRI) in Peritoneal Carcinomatosis From Gastrointestinal Cancer

Intraperitoneal Aerosolized Nanoliposomal Irinotecan (Nal-IRI) in Peritoneal Carcinomatosis From Gastrointestinal Cancer: a Phase I Study

This will be determined in plasma and tissue samples. This outcome evaluates anti-cancer efficacy.

This will be determined in plasma and tissue samples. This outcome evaluates conversion of CPT-11 to SN-38 between patients.

Dose limiting toxicities will be monitored.

Define the dose recommended to use in a follow-up phase 2 trial based on incidence of DLT and toxicity data scored with CTCAE v5.0 for chemotherapy related toxicity.

This will be estimated with the Dindo-Clavien classification and the comprehensive complication index (CCI).

Determined for CPT-11, SN-38 and SN-38G in plasma and tumor tissue using UPLC-MS/MS.

Evaluated on tumor biopsies to determine histological treatment response

Tumour samples will be collected at the end of the aerosol delivery after each PIPAC procedure.

To evaluate patient's follow-up, several time-to-event endpoints are recorded which include: overall survival (OS), progression free survival (PFS) and peritoneal progression free survival (PPFS).

This will be investigated using the EORTC QLQ-C30 questionnaire. As to question 1 to 28: the scale varies from 1 (not at all) to 4 (very much). A higher value indicates a lower quality of life. The total score will be between 28 and 112.

The scale of question 29 and 30 varies from 1 (very poor) to 7 (excellent). The higher the value, the better the quality of life. The total score will be between 2 and 14

This will be investigated using the FACT-G questionnaire. The scale of all questions varies from 0 (not at all) to 4 (very much). The total score will be between 0 and 108. The lower the total score, the better the quality of life.

This will be investigated using the PRO-CTCAE™ questionnaire. The scale of all questions varies from 0 to 4 or 0 to 1 representing absent/present. PRO-CTCAE scores for each attribute (frequency, severity and/or interference) should be presented descriptively (eg. summary statistics or graphical presentations).

With this score, pain is assessed on a horizontal line, 100 mm in length, anchored by word descriptors at each end, no pain and very severe pain respectively. The patient marks on the line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimeters from the left-hand end of the line to the point that the patient marks.

Determined according to the RECIST criteria, if possible (measurable lesions on CT or MRI). When no target lesions available, overall treatment response (stable disease, partial response, or progressive disease) will be determined by incorporating PRGS, clinical signs and symptoms, tumor markers, imaging findings (other than target lesions, e.g. ascites volume).

Spots Global Cancer Trial Database for primary gastrointestinal cancer