Clinical trial NCT04779554: Flat Dose vs. Weight-based IP Chemotherapy for CRS/HIPEC
Official title: A Randomized Phase 2 Trial of Flat Dose vs. Weight-based Dose of Intra-peritoneal (IP) Chemotherapy for Patients Undergoing Cytoreductive Surgery and Heated Intra-peritoneal Chemotherapy (CRS/HIPEC) for Advanced Gastrointestinal Malignancy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Peritoneal Carcinomatosis
Keywords: cytoreductive surgery
colorectal cancer
pseudomyxoma peritonei
appendiceal mucinous neoplasm
mitomycin C
pharmacokinetics
CRS/HIPEC
HIPEC
Appendix cancer
LAMN
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2021-03-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with one of the following: low-grade appendiceal mucinous neoplasm, 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

Primary outcomes:
measure: Area Under the Curve (AUC) - Pharmacokinetics
timeFrame: Approximately 20 hours
measure: Drug Clearance (CL) - Pharmacokinetics
timeFrame: Approximately 20 hours
measure: Drug Half-Life (T1/2) - Pharmacokinetics
timeFrame: Approximately 20 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
Study officials:
affiliation: University of Kentucky
name: Prakash Pandalai, MD
role: PRINCIPAL_INVESTIGATOR
References: