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-Reference-Cited by-同舟云学术

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

Published:2022-06-21 Issue:4 Volume:7 Page:169-177
ISSN:2364-768X
Container-title:Pleura and Peritoneum
language:en
Short-container-title:

Author:

Raoof Mustafa¹,Sullivan Kevin M.¹,Frankel Paul H.²,Fakih Marwan³,Synold Timothy W.⁴,Lim Dean³,Woo Yanghee¹,Paz Isaac Benjamin¹,Fong Yuman¹,Thomas Rebecca Meera⁵,Chang Sue⁶,Eng Melissa⁷,Tinsley Raechelle⁷,Whelan Richard L.⁸,Deperalta Danielle⁸,Reymond Marc A.⁹,Jones Jeremy¹⁰,Merchea Amit¹¹,Dellinger Thanh H.¹^ORCID

Affiliation:

1. Department of Surgery , Division of Surgical Oncology, City of Hope National Medical Center , Duarte , CA , USA

2. Department of Computation and Quantitative Medicine , City of Hope National Medical Center , Duarte , CA , USA

3. Department of Medical Oncology and Therapeutics , City of Hope National Medical Center , Duarte , CA , USA

4. Analytical Pharmacology Core , City of Hope Comprehensive Cancer Center , Duarte , CA , USA

5. Department of Pathology , Northwell Health , New York , NY , USA

6. Department of Pathology , City of Hope National Medical Center , Duarte , CA , USA

7. Office of Clinical Research , City of Hope National Medical Center , Duarte , CA , USA

8. Department of Surgery , Northwell Health, Donald and Barbara Zucker School of Medicine , New Hyde Park , NY , USA

9. Department of Surgery , University of Tuebingen , Tubingen , Germany

10. Department of Oncology (Medical) , Mayo Clinic , Jacksonville , FL , USA

11. Department of Surgery , Mayo Clinic , Jacksonville , FL , USA

Abstract

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.

Publisher

Walter de Gruyter GmbH

Subject

Internal Medicine

Link

https://www.degruyter.com/document/doi/10.1515/pp-2022-0116/pdf

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