Peritoneal Carcinomatosis
Conditions
Keywords
cytoreductive surgery, colorectal cancer, pseudomyxoma peritonei, appendiceal mucinous neoplasm, mitomycin C, pharmacokinetics, CRS/HIPEC, HIPEC, Appendix cancer, LAMN
Brief summary
Peritoneal carcinomatosis from advanced gastro-intestinal malignancy has historically been associated with poor overall survival (≤ 12 months) with few treatment options. Cytoreductive surgery (CRS), which involves removal of all macroscopic tumor nodules, combined with direct administration of heated intra-peritoneal (IP) chemotherapy (HIPEC) to the affected peritoneal surfaces, has been shown to be an effective treatment option that extends overall survival among certain cases of peritoneal carcinomatosis. IP chemotherapy allows delivery of a high dose of cytostatic drug directly onto the peritoneal surfaces at risk for microscopic residual disease while systemic exposure remains limited. Additionally, hyperthermia is known to enhance the cytotoxicity of several agents (including Mitomycin C) and improves the depth of peritoneal penetration. This trial will be a randomized phase 2 comparison of flat dose versus weight-based dose Mitomycin C. The hypothesis of this study is that HIPEC weight-based dosing may result in similarly effective peritoneal Mitomycin C concentrations with less systemic absorption and potential systemic toxicity, compared with the HIPEC flat dosing approach in patients undergoing CRS/HIPEC.
Interventions
DRUGMitomycin C, flat dose 40 mg
Mitomycin C will be delivered as heated intraperitoneal chemotherapy (HIPEC) in two flat doses. Dose 1 will be 30mg at minute 0 and dose 2 will be 10 mg at minute 45.
DRUGMitomycin C, weight-based dose 12.5 mg/m2
Mitomycin C will be delivered as heated intraperitoneal chemotherapy (HIPEC) in two weight-based doses of 9.5 mg/m2 at minute 0 and 3 mg/m2 at minute 45.
Sponsors
Prakash Pandalai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with one of the following: low-grade appendiceal mucinous neoplasm, pseudomyxoma peritonei, appendiceal cancer with peritoneal carcinomatosis, colorectal cancer with peritoneal carcinomatosis * ECOG performance status \< 3 * Candidate for grossly complete cytoreductive surgery * Life expectancy greater than 3 months * Adequate organ and marrow function * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Any extra-abdominal metastases * Untreated lung metastases * Liver metastases not amenable to resection or ablation * Known brain metastases * Chemotherapy or radiotherapy within 4 weeks prior to entering the study * Presence of residual significant adverse events attributed to prior cancer treatment * Currently receiving any other investigational therapeutic agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Mitomycin C. * Pregnant or breast-feeding women * Uncontrolled ongoing illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) - Pharmacokinetics | Approximately 20 hours | Drug exposure will be measured by calculating the area under the curve (AUC) or integral of a plasma concentration-time curve. Samples will be collected at 0,15, 30, 60 and 90 minutes intra-operatively, and 2, 4, and 12 hours postoperatively. |
| Drug Clearance (CL) - Pharmacokinetics | Approximately 20 hours | Drug clearance will be calculated as the volume of plasma cleared per unit time. Samples will be collected at 0,15, 30, 60 and 90 minutes intra-operatively, and 2, 4, and 12 hours postoperatively. |
| Drug Half-Life (T1/2) - Pharmacokinetics | Approximately 20 hours | Drug half-life will be calculated as the time required for the plasma Mitomycin C concentration to be half of its maximum concentration. Samples will be collected at 0,15, 30, 60 and 90 minutes intra-operatively, and 2, 4, and 12 hours postoperatively. |
Countries
United States
Contacts
CONTACTPrakash Pandalai, MD
PRINCIPAL_INVESTIGATORPrakash Pandalai, MD
University of Kentucky
Outcome results
None listed