Pressurized Intraperitoneal Aerosolized Chemotherapy With Mitomycin for the Treatment of Unresectable Appendix or Colorectal Cancer With Peritoneal Metastases, The IMPACT Trial

Inclusion Criteria

• •Documented informed consent of the participant and/or legally authorized representative
• •* Assent, when appropriate, will be obtained per institutional guidelines
• •Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• •* If unavailable, exceptions may be granted with study principal investigator (PI) approval
• •Age: ≥ 18 years
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• •Histologically or cytologically confirmed appendiceal or colorectal cancer peritoneal metastases
• •No extraperitoneal metastases except lung ≤ 5 lesions with largest ≤ 1cm as identified on CT imaging or MRI. CT scan or MRI to assess measurable disease must have been completed within 28 days prior to registration
• •Visible peritoneal metastatic disease on cross-sectional imaging or diagnostic laparoscopy (does not have to be measurable by RECIST (v1.1)
• •Completed at least 4 months (8 cycles) of first-line standard-of-care oxaliplatin-based systemic therapy without progression of disease. Or completed less than 4 months of oxaliplatin based therapy due to intolerance and without progressive disease. Or progressed on first-line standard-of-care oxaliplatin-based systemic therapy. Permissible first-line systemic therapies include leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) or fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFOXIRI). Receipt of anti-EGFR, anti-VEGF, or anti-BRAF therapy in the first-line is acceptable. Mismatch repair-deficient patients are permissible if they have progressed on first-line immunotherapy
• •Not a candidate for cytoreductive surgery as determined by site investigator
• •Fully recovered from the acute toxic effects of prior anti-cancer therapy to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or lower except alopecia, hearing loss, neuropathy, or non-clinically significant laboratory abnormalities
• •Complete medical history and physical exam (To be performed within 28 days prior to Day 1 of protocol therapy)
• •Absolute neutrophil count (ANC) ≥ 1,500/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)
• •Platelets ≥ 100,000/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)
• •Hemoglobin ≥ 8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
• •Serum albumin ≥ 2.8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
• •Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease, then direct bilirubin \< 1.5 mg/dL) (To be performed within 28 days prior to Day 1 of protocol therapy)
• •Aspartate aminotransferase (AST) ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
• •Alanine aminotransferase (ALT) ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
• •Calculated creatinine clearance of ≥ 45 mL/min per 24-hour urine test or the Cockcroft-Gault formula (To be performed within 28 days prior to Day 1 of protocol therapy)
• •Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test (To be performed within 28 days prior to Day 1 of protocol therapy)
• •* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• •Agreement by females and males of childbearing potential to use an effective method of birth control (e.g. licensed hormonal/barrier methods or surgery intended to prevent pregnancy \[or with a side effect of pregnancy prevention\]) or abstain from heterosexual activity for the course of the study through at least 14 months after the last dose of protocol therapy
• •* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
• •CROSS-OVER ARM INCLUSION: Documented informed consent of the participant and/or legally authorized representative
• •* Assent, when appropriate, will be obtained per institutional guidelines
• •CROSS-OVER ARM INCLUSION: Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• •* If unavailable, exceptions may be granted with Study PI approval
• •CROSS-OVER ARM INCLUSION: Age: ≥ 18 years
• •CROSS-OVER ARM INCLUSION: ECOG performance status of 0 or 1
• •CROSS-OVER ARM INCLUSION: No extraperitoneal metastases except lung ≤ 5 lesions with largest ≤ 1cm as identified on CT imaging or MRI. CT scan or MRI to assess measurable disease must have been completed within 28 days prior to registration
• •CROSS-OVER ARM INCLUSION: Progression on Control Arm of the Study as determined by RECIST v1.1. Non-radiographic progression will need to be assessed on a case-by-case basis by central review
• •CROSS-OVER ARM INCLUSION: Fully recovered from the acute toxic effects of prior anti-cancer therapy to CTCAE grade 1 or lower except alopecia, hearing loss, neuropathy, or non-clinically significant laboratory abnormalities
• •CROSS-OVER ARM INCLUSION: Complete medical history and physical exam (To be performed within 28 days prior to Day 1 of protocol therapy)
• •CROSS-OVER ARM INCLUSION: ANC ≥ 1,500/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)
• •CROSS-OVER ARM INCLUSION: Platelets ≥ 100,000/mcL (To be performed within 28 days prior to Day 1 of protocol therapy)
• •CROSS-OVER ARM INCLUSION: Hemoglobin ≥ 8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
• •CROSS-OVER ARM INCLUSION: Serum albumin ≥ 2.8 g/dL (To be performed within 28 days prior to Day 1 of protocol therapy)
• •CROSS-OVER ARM INCLUSION: Total bilirubin ≤ 1.5 X ULN (unless has Gilbert's disease, then direct bilirubin \<1.5 mg/dL) (To be performed within 28 days prior to Day 1 of protocol therapy)
• •CROSS-OVER ARM INCLUSION: AST ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
• •CROSS-OVER ARM INCLUSION: ALT ≤ 5 x ULN (To be performed within 28 days prior to Day 1 of protocol therapy)
• •CROSS-OVER ARM INCLUSION: Calculated creatinine clearance of ≥ 45 mL/min per 24-hour urine test or the Cockcroft-Gault formula (To be performed within 28 days prior to Day 1 of protocol therapy)
• •CROSS-OVER ARM INCLUSION: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (To be performed within 28 days prior to Day 1 of protocol therapy)
• •* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• •CROSS-OVER ARM INCLUSION: Agreement by females and males of childbearing potential to use an effective method of birth control (e.g. licensed hormonal/barrier methods or surgery intended to prevent pregnancy \[or with a side effect of pregnancy prevention\]) or abstain from heterosexual activity for the course of the study through at least 14 months after the last dose of protocol therapy
• •* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)