Adjuvant Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in resected high-risk colon cancer patients – study protocol for the PIPAC-OPC3 Trial. A prospective, controlled phase 2 Study

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Background: Peritoneal metastasis (PM) is the second most common site of recurrence in colon cancer (CC) patients and accounts for approximately one-third of all recurrences. Patients with T4 or intraperitoneal perforated colon cancers have an increased risk of developing PM, and since manifest PM is difficult to treat, high-risk patients should be offered prophylactic treatment. Here, we propose a study of adjuvant oxaliplatin administered as pressurized intraperitoneal aerosol chemotherapy (PIPAC OX) in patients with high-risk colon cancer (T4, perforated tumors, ovarian metastasis).

Methods: PIPAC-OPC3 CC is a non-randomized, non-blinded phase 2 cohort study designed to treat high-risk colon cancer patients with adjuvant PIPAC-directed therapy. Based on an expected 90 % peritoneal recurrence-free survival with adjuvant PIPAC against the estimated 75 % without, 60 patients are needed (α: 0.05, power: 0.8). Eligible patients will receive two PIPAC treatments with oxaliplatin (92 mg/m 2) at 4-6 week intervals. During laparoscopy, the peritoneum is biopsied at two locations, and peritoneal lavage with 500 mL of saline and laparoscopic ultrasound is performed. The patients are screened for adverse medical events and surgery-related complications after each PIPAC procedure. After the second PIPAC procedure, the patients will be examined in the outpatient clinic and followed with CT scans 12, 24 and 36 months after resection. The primary outcome of the PIPAC-OPC3 CC trial is to evaluate if PIPAC-directed adjuvant therapy can reduce the risk of PM. Secondary outcomes include the number of conversions from positive to negative peritoneal lavage cytology after one PIPAC procedure, completion rate of two adjuvant PIPAC treatments, toxicity and complication rate and recurrence-free and overall survival rates after 1, 3 and 5 years.

Results: It is expected that PIPAC-directed adjuvant therapy can provide an absolute risk reduction of 15 % regarding the development of PM in high-risk colon cancer patients, and that this may result in increased survival rates. We expect that free intraperitoneal tumor cells (FITC) may be detected by peritoneal lavage performed just prior to the administration of PIPAC-directed therapy, and that this treatment may convert FITC-positive patients to a FITC-negative status.

Conclusions: This study may provide important knowledge to be used in designing additional studies on PIPAC in the adjuvant setting of other primary cancers.

Trial registration: ClinicalTrials.gov Identifier NCT03280511 (2017-09-12). European Clinical Trials Database (EudraCT) 2017-002637-37.

OriginalsprogEngelsk
Artikelnummer20180107
TidsskriftPleura and Peritoneum
Vol/bind3
Udgave nummer2
Antal sider7
ISSN2364-7671
DOI
StatusUdgivet - 1. jun. 2018

Fingeraftryk

Colonic Neoplasms
oxaliplatin
Peritoneal Lavage
Adjuvant Chemotherapy
Neoplasms
Survival Rate
Numbers Needed To Treat
Ambulatory Care Facilities
Cell Biology
Cohort Studies
Clinical Trials
Databases

Citer dette

@article{6d10193d4c7d4c32bf2ee8d3f9dafecf,
title = "Adjuvant Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in resected high-risk colon cancer patients – study protocol for the PIPAC-OPC3 Trial. A prospective, controlled phase 2 Study",
abstract = "Background: Peritoneal metastasis (PM) is the second most common site of recurrence in colon cancer (CC) patients and accounts for approximately one-third of all recurrences. Patients with T4 or intraperitoneal perforated colon cancers have an increased risk of developing PM, and since manifest PM is difficult to treat, high-risk patients should be offered prophylactic treatment. Here, we propose a study of adjuvant oxaliplatin administered as pressurized intraperitoneal aerosol chemotherapy (PIPAC OX) in patients with high-risk colon cancer (T4, perforated tumors, ovarian metastasis).Methods: PIPAC-OPC3 CC is a non-randomized, non-blinded phase 2 cohort study designed to treat high-risk colon cancer patients with adjuvant PIPAC-directed therapy. Based on an expected 90 {\%} peritoneal recurrence-free survival with adjuvant PIPAC against the estimated 75 {\%} without, 60 patients are needed (α: 0.05, power: 0.8). Eligible patients will receive two PIPAC treatments with oxaliplatin (92 mg/m 2) at 4-6 week intervals. During laparoscopy, the peritoneum is biopsied at two locations, and peritoneal lavage with 500 mL of saline and laparoscopic ultrasound is performed. The patients are screened for adverse medical events and surgery-related complications after each PIPAC procedure. After the second PIPAC procedure, the patients will be examined in the outpatient clinic and followed with CT scans 12, 24 and 36 months after resection. The primary outcome of the PIPAC-OPC3 CC trial is to evaluate if PIPAC-directed adjuvant therapy can reduce the risk of PM. Secondary outcomes include the number of conversions from positive to negative peritoneal lavage cytology after one PIPAC procedure, completion rate of two adjuvant PIPAC treatments, toxicity and complication rate and recurrence-free and overall survival rates after 1, 3 and 5 years. Results: It is expected that PIPAC-directed adjuvant therapy can provide an absolute risk reduction of 15 {\%} regarding the development of PM in high-risk colon cancer patients, and that this may result in increased survival rates. We expect that free intraperitoneal tumor cells (FITC) may be detected by peritoneal lavage performed just prior to the administration of PIPAC-directed therapy, and that this treatment may convert FITC-positive patients to a FITC-negative status.Conclusions: This study may provide important knowledge to be used in designing additional studies on PIPAC in the adjuvant setting of other primary cancers.Trial registration: ClinicalTrials.gov Identifier NCT03280511 (2017-09-12). European Clinical Trials Database (EudraCT) 2017-002637-37.",
author = "Martin Graversen and S{\"o}nke Detlefsen and Fristrup, {Claus Wilki} and Per Pfeiffer and Mortensen, {Michael Bau}",
year = "2018",
month = "6",
day = "1",
doi = "10.1515/pp-2018-0107",
language = "English",
volume = "3",
journal = "Pleura and Peritoneum",
issn = "2364-7671",
publisher = "Walterde Gruyter GmbH",
number = "2",

}

TY - JOUR

T1 - Adjuvant Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in resected high-risk colon cancer patients – study protocol for the PIPAC-OPC3 Trial. A prospective, controlled phase 2 Study

AU - Graversen, Martin

AU - Detlefsen, Sönke

AU - Fristrup, Claus Wilki

AU - Pfeiffer, Per

AU - Mortensen, Michael Bau

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background: Peritoneal metastasis (PM) is the second most common site of recurrence in colon cancer (CC) patients and accounts for approximately one-third of all recurrences. Patients with T4 or intraperitoneal perforated colon cancers have an increased risk of developing PM, and since manifest PM is difficult to treat, high-risk patients should be offered prophylactic treatment. Here, we propose a study of adjuvant oxaliplatin administered as pressurized intraperitoneal aerosol chemotherapy (PIPAC OX) in patients with high-risk colon cancer (T4, perforated tumors, ovarian metastasis).Methods: PIPAC-OPC3 CC is a non-randomized, non-blinded phase 2 cohort study designed to treat high-risk colon cancer patients with adjuvant PIPAC-directed therapy. Based on an expected 90 % peritoneal recurrence-free survival with adjuvant PIPAC against the estimated 75 % without, 60 patients are needed (α: 0.05, power: 0.8). Eligible patients will receive two PIPAC treatments with oxaliplatin (92 mg/m 2) at 4-6 week intervals. During laparoscopy, the peritoneum is biopsied at two locations, and peritoneal lavage with 500 mL of saline and laparoscopic ultrasound is performed. The patients are screened for adverse medical events and surgery-related complications after each PIPAC procedure. After the second PIPAC procedure, the patients will be examined in the outpatient clinic and followed with CT scans 12, 24 and 36 months after resection. The primary outcome of the PIPAC-OPC3 CC trial is to evaluate if PIPAC-directed adjuvant therapy can reduce the risk of PM. Secondary outcomes include the number of conversions from positive to negative peritoneal lavage cytology after one PIPAC procedure, completion rate of two adjuvant PIPAC treatments, toxicity and complication rate and recurrence-free and overall survival rates after 1, 3 and 5 years. Results: It is expected that PIPAC-directed adjuvant therapy can provide an absolute risk reduction of 15 % regarding the development of PM in high-risk colon cancer patients, and that this may result in increased survival rates. We expect that free intraperitoneal tumor cells (FITC) may be detected by peritoneal lavage performed just prior to the administration of PIPAC-directed therapy, and that this treatment may convert FITC-positive patients to a FITC-negative status.Conclusions: This study may provide important knowledge to be used in designing additional studies on PIPAC in the adjuvant setting of other primary cancers.Trial registration: ClinicalTrials.gov Identifier NCT03280511 (2017-09-12). European Clinical Trials Database (EudraCT) 2017-002637-37.

AB - Background: Peritoneal metastasis (PM) is the second most common site of recurrence in colon cancer (CC) patients and accounts for approximately one-third of all recurrences. Patients with T4 or intraperitoneal perforated colon cancers have an increased risk of developing PM, and since manifest PM is difficult to treat, high-risk patients should be offered prophylactic treatment. Here, we propose a study of adjuvant oxaliplatin administered as pressurized intraperitoneal aerosol chemotherapy (PIPAC OX) in patients with high-risk colon cancer (T4, perforated tumors, ovarian metastasis).Methods: PIPAC-OPC3 CC is a non-randomized, non-blinded phase 2 cohort study designed to treat high-risk colon cancer patients with adjuvant PIPAC-directed therapy. Based on an expected 90 % peritoneal recurrence-free survival with adjuvant PIPAC against the estimated 75 % without, 60 patients are needed (α: 0.05, power: 0.8). Eligible patients will receive two PIPAC treatments with oxaliplatin (92 mg/m 2) at 4-6 week intervals. During laparoscopy, the peritoneum is biopsied at two locations, and peritoneal lavage with 500 mL of saline and laparoscopic ultrasound is performed. The patients are screened for adverse medical events and surgery-related complications after each PIPAC procedure. After the second PIPAC procedure, the patients will be examined in the outpatient clinic and followed with CT scans 12, 24 and 36 months after resection. The primary outcome of the PIPAC-OPC3 CC trial is to evaluate if PIPAC-directed adjuvant therapy can reduce the risk of PM. Secondary outcomes include the number of conversions from positive to negative peritoneal lavage cytology after one PIPAC procedure, completion rate of two adjuvant PIPAC treatments, toxicity and complication rate and recurrence-free and overall survival rates after 1, 3 and 5 years. Results: It is expected that PIPAC-directed adjuvant therapy can provide an absolute risk reduction of 15 % regarding the development of PM in high-risk colon cancer patients, and that this may result in increased survival rates. We expect that free intraperitoneal tumor cells (FITC) may be detected by peritoneal lavage performed just prior to the administration of PIPAC-directed therapy, and that this treatment may convert FITC-positive patients to a FITC-negative status.Conclusions: This study may provide important knowledge to be used in designing additional studies on PIPAC in the adjuvant setting of other primary cancers.Trial registration: ClinicalTrials.gov Identifier NCT03280511 (2017-09-12). European Clinical Trials Database (EudraCT) 2017-002637-37.

U2 - 10.1515/pp-2018-0107

DO - 10.1515/pp-2018-0107

M3 - Journal article

VL - 3

JO - Pleura and Peritoneum

JF - Pleura and Peritoneum

SN - 2364-7671

IS - 2

M1 - 20180107

ER -