TY - JOUR
T1 - Multicenter dose-escalation Phase i trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for appendiceal and colorectal peritoneal metastases
T2 - Rationale and design
AU - Raoof, Mustafa
AU - Sullivan, Kevin M.
AU - Frankel, Paul H.
AU - Fakih, Marwan
AU - Synold, Timothy W.
AU - Lim, Dean
AU - Woo, Yanghee
AU - Paz, Isaac Benjamin
AU - Fong, Yuman
AU - Thomas, Rebecca Meera
AU - Chang, Sue
AU - Eng, Melissa
AU - Tinsley, Raechelle
AU - Whelan, Richard L.
AU - Deperalta, Danielle
AU - Reymond, Marc A.
AU - Jones, Jeremy
AU - Merchea, Amit
AU - Dellinger, Thanh H.
N1 - Publisher Copyright:
© 2022 the author(s), published by De Gruyter, Berlin/Boston.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Objectives: Peritoneal metastasis (PM) from appendiceal cancer or colorectal cancer (CRC) has significant morbidity and limited survival. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a minimally invasive approach to treat PM. We aim to conduct a dose-escalation trial of mitomycin C (MMC)-PIPAC combined with systemic chemotherapy (FOLFIRI) in patients with PM from appendiceal cancer or CRC. Methods: This is a multicenter Phase I study of MMC-PIPAC (NCT04329494). Inclusion criteria include treatment with at least 4 months of first- or second-line systemic chemotherapy with ineligibility for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Exclusion criteria are: progression on chemotherapy; extraperitoneal metastases; systemic chemotherapy intolerance; bowel obstruction; or poor performance status (ECOG>2). Escalating MMC-PIPAC doses (7-25 mg/m2) will be administered in combination with standard dose systemic FOLFIRI. Safety evaluation will be performed on 15 patients (dose escalation) and six expansion patients: 21 evaluable patients total. Results: The primary endpoints are recommended MMC dose and safety of MMC-PIPAC with FOLFIRI. Secondary endpoints are assessment of response (by peritoneal regression grade score; Response Evaluation Criteria in Solid Tumors [RECIST 1.1], and peritoneal carcinomatosis index), progression free survival, overall survival, technical failure rate, surgical complications, conversion to curative-intent CRS-HIPEC, patient-reported outcomes, and functional status. Longitudinal blood and tissue specimens will be collected for translational correlatives including pharmacokinetics, circulating biomarkers, immune profiling, and single-cell transcriptomics. Conclusions: This Phase I trial will establish the recommended dose of MMC-PIPAC in combination with FOLFIRI. Additionally, we expect to detect an early efficacy signal for further development of this therapeutic combination.
AB - Objectives: Peritoneal metastasis (PM) from appendiceal cancer or colorectal cancer (CRC) has significant morbidity and limited survival. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a minimally invasive approach to treat PM. We aim to conduct a dose-escalation trial of mitomycin C (MMC)-PIPAC combined with systemic chemotherapy (FOLFIRI) in patients with PM from appendiceal cancer or CRC. Methods: This is a multicenter Phase I study of MMC-PIPAC (NCT04329494). Inclusion criteria include treatment with at least 4 months of first- or second-line systemic chemotherapy with ineligibility for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Exclusion criteria are: progression on chemotherapy; extraperitoneal metastases; systemic chemotherapy intolerance; bowel obstruction; or poor performance status (ECOG>2). Escalating MMC-PIPAC doses (7-25 mg/m2) will be administered in combination with standard dose systemic FOLFIRI. Safety evaluation will be performed on 15 patients (dose escalation) and six expansion patients: 21 evaluable patients total. Results: The primary endpoints are recommended MMC dose and safety of MMC-PIPAC with FOLFIRI. Secondary endpoints are assessment of response (by peritoneal regression grade score; Response Evaluation Criteria in Solid Tumors [RECIST 1.1], and peritoneal carcinomatosis index), progression free survival, overall survival, technical failure rate, surgical complications, conversion to curative-intent CRS-HIPEC, patient-reported outcomes, and functional status. Longitudinal blood and tissue specimens will be collected for translational correlatives including pharmacokinetics, circulating biomarkers, immune profiling, and single-cell transcriptomics. Conclusions: This Phase I trial will establish the recommended dose of MMC-PIPAC in combination with FOLFIRI. Additionally, we expect to detect an early efficacy signal for further development of this therapeutic combination.
KW - Phase I study
KW - appendiceal cancer
KW - colorectal cancer (CRC)
KW - mitomycin C (MMC)
KW - peritoneal metastasis (PM)
KW - pressurized intraperitoneal aerosolized chemotherapy (PIPAC)
UR - http://www.scopus.com/inward/record.url?scp=85137436715&partnerID=8YFLogxK
U2 - 10.1515/pp-2022-0116
DO - 10.1515/pp-2022-0116
M3 - Article
AN - SCOPUS:85137436715
SN - 2364-768X
VL - 7
SP - 169
EP - 177
JO - Pleura and Peritoneum
JF - Pleura and Peritoneum
IS - 4
ER -