Flat Dose vs. Weight-based IP Chemotherapy for CRS/HIPEC

NCT04779554 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-20-GI-115
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

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.

Conditions

Peritoneal Carcinomatosis

Keywords

cytoreductive surgery; colorectal cancer; pseudomyxoma peritonei; appendiceal mucinous neoplasm; mitomycin C; pharmacokinetics; CRS/HIPEC; HIPEC; Appendix cancer; LAMN

Outcome Measures

Primary Outcomes (3)

• Area Under the Curve (AUC) - Pharmacokinetics

  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.

  Approximately 20 hours

• Drug Clearance (CL) - Pharmacokinetics

  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.

  Approximately 20 hours

• Drug Half-Life (T1/2) - Pharmacokinetics

  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.

  Approximately 20 hours

Study Arms (2)

Flat Dose Mitomycin C

EXPERIMENTAL

Participants in this group will receive flat doses of mitomycin C intra-operatively: 1) 30mg at minute 0 and 2) 10mg at minute 45. Mitomycin C will be delivered via HIPEC (hyperthermic intraperitoneal chemotherapy).

Drug: Mitomycin C, flat dose 40 mg

Weight-Based Mitomycin C

EXPERIMENTAL

Participants in this group will receive weight-based dosing of mitomycin C intra-operatively: 1) 9.5 mg/m2 at minute 0 and 2) 3 mg/m2 at minute 45 for total dose of 12.5 mg/m2. Mitomycin C will be delivered via HIPEC (hyperthermic intraperitoneal chemotherapy).

Drug: Mitomycin C, weight-based dose 12.5 mg/m2

Interventions

Mitomycin C, flat dose 40 mg DRUG

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.

Flat Dose Mitomycin C

Mitomycin C, weight-based dose 12.5 mg/m2 DRUG

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.

Weight-Based Mitomycin C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prakash Pandalai: lead

Study Sites (2)

University of Kentucky

Lexington, Kentucky, 40536, United States

RECRUITING

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

RECRUITING

Related Publications (1)

• McDonald HG, Cassim EB, Harper MM, Burke EE, Marcinkowski EF, Cavnar MJ, Pandalai PK, Kim J. The Development of Investigator-Initiated Clinical Trials in Surgical Oncology. Surg Oncol Clin N Am. 2023 Jan;32(1):13-25. doi: 10.1016/j.soc.2022.07.003. Epub 2022 Nov 3.

  PMID: 36410913 DERIVED

MeSH Terms

Conditions

Peritoneal Neoplasms; Colorectal Neoplasms; Pseudomyxoma Peritonei; Appendiceal Neoplasms

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma, Mucinous; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Cystic, Mucinous, and Serous; Cecal Neoplasms; Cecal Diseases

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Prakash Pandalai, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prakash Pandalai, MD

CONTACT

859-323-8920; Prakash.Pandalai@uky.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 27, 2021
• First Posted: March 3, 2021
• Study Start: June 4, 2021
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)