Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Pleura and peritoneum, 2022-12, Vol.7 (4), p.169-177

Ort / Verlag

Germany: De Gruyter

Erscheinungsjahr

2022

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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. 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/m ) 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. 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. 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.