Multicenter dose-escalation Phase i trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for appendiceal and colorectal peritoneal metastases: Rationale and design

Mustafa Raoof; Kevin M. Sullivan; Paul H. Frankel; Marwan Fakih; Timothy W. Synold; Dean Lim; Yanghee Woo; Isaac Benjamin Paz; Yuman Fong; Rebecca Meera Thomas; Sue Chang; Melissa Eng; Raechelle Tinsley; Richard L. Whelan; Danielle Deperalta; Marc A. Reymond; Jeremy Jones; Amit Merchea; Thanh H. Dellinger

doi:10.1515/pp-2022-0116

Multicenter dose-escalation Phase i trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for appendiceal and colorectal peritoneal metastases: Rationale and design

Mustafa Raoof
, Kevin M. Sullivan
, Paul H. Frankel
, Marwan Fakih
, Timothy W. Synold
, Dean Lim
, Yanghee Woo
, Isaac Benjamin Paz
, Yuman Fong
, Rebecca Meera Thomas
, Sue Chang
, Melissa Eng
, Raechelle Tinsley
, Richard L. Whelan
, Danielle Deperalta
, Marc A. Reymond
, Jeremy Jones
, Amit Merchea
, Thanh H. Dellinger

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	169-177
Number of pages	9
Journal	Pleura and Peritoneum
Volume	7
Issue number	4
DOIs	https://doi.org/10.1515/pp-2022-0116
State	Published - 1 Dec 2022
Externally published	Yes

Keywords

Phase I study
appendiceal cancer
colorectal cancer (CRC)
mitomycin C (MMC)
peritoneal metastasis (PM)
pressurized intraperitoneal aerosolized chemotherapy (PIPAC)

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Raoof, M., Sullivan, K. M., Frankel, P. H., Fakih, M., Synold, T. W., Lim, D., Woo, Y., Paz, I. B., Fong, Y., Thomas, R. M., Chang, S., Eng, M., Tinsley, R., Whelan, R. L., Deperalta, D., Reymond, M. A., Jones, J., Merchea, A., & Dellinger, T. H. (2022). Multicenter dose-escalation Phase i trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for appendiceal and colorectal peritoneal metastases: Rationale and design. Pleura and Peritoneum, 7(4), 169-177. https://doi.org/10.1515/pp-2022-0116

@article{f0ba61a3aed84801b93cc9b2fe352ce2,

title = "Multicenter dose-escalation Phase i trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for appendiceal and colorectal peritoneal metastases: Rationale and design",

abstract = "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.",

keywords = "Phase I study, appendiceal cancer, colorectal cancer (CRC), mitomycin C (MMC), peritoneal metastasis (PM), pressurized intraperitoneal aerosolized chemotherapy (PIPAC)",

author = "Mustafa Raoof and Sullivan, \{Kevin M.\} and Frankel, \{Paul H.\} and Marwan Fakih and Synold, \{Timothy W.\} and Dean Lim and Yanghee Woo and Paz, \{Isaac Benjamin\} and Yuman Fong and Thomas, \{Rebecca Meera\} and Sue Chang and Melissa Eng and Raechelle Tinsley and Whelan, \{Richard L.\} and Danielle Deperalta and Reymond, \{Marc A.\} and Jeremy Jones and Amit Merchea and Dellinger, \{Thanh H.\}",

note = "Publisher Copyright: {\textcopyright} 2022 the author(s), published by De Gruyter, Berlin/Boston.",

year = "2022",

month = dec,

day = "1",

doi = "10.1515/pp-2022-0116",

language = "English",

volume = "7",

pages = "169--177",

journal = "Pleura and Peritoneum",

issn = "2364-768X",

publisher = "Walter de Gruyter GmbH",

number = "4",

}

Raoof, M, Sullivan, KM, Frankel, PH, Fakih, M, Synold, TW, Lim, D, Woo, Y, Paz, IB, Fong, Y, Thomas, RM, Chang, S, Eng, M, Tinsley, R, Whelan, RL, Deperalta, D, Reymond, MA, Jones, J, Merchea, A & Dellinger, TH 2022, 'Multicenter dose-escalation Phase i trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for appendiceal and colorectal peritoneal metastases: Rationale and design', Pleura and Peritoneum, vol. 7, no. 4, pp. 169-177. https://doi.org/10.1515/pp-2022-0116

Multicenter dose-escalation Phase i trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for appendiceal and colorectal peritoneal metastases: Rationale and design. / Raoof, Mustafa; Sullivan, Kevin M.; Frankel, Paul H. et al.
In: Pleura and Peritoneum, Vol. 7, No. 4, 01.12.2022, p. 169-177.

Research output: Contribution to journal › Article › peer-review

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.

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 - https://www.scopus.com/pages/publications/85137436715

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 -