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

Primary Purpose

Peritoneal Carcinomatosis

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Mitomycin C, flat dose 40 mg

Mitomycin C, weight-based dose 12.5 mg/m2

About this trial

This is an interventional treatment trial for Peritoneal Carcinomatosis focused on measuring cytoreductive surgery, colorectal cancer, pseudomyxoma peritonei, appendiceal mucinous neoplasm, mitomycin C, pharmacokinetics, CRS/HIPEC, HIPEC, Appendix cancer, LAMN

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of KentuckyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Flat Dose Mitomycin C

Weight-Based Mitomycin C

Arm Description

Participants in this group will receive flat doses of mitomycin C intra-operatively: 1) 30mg at minute 0 and 2) 10mg at minute 60. Mitomycin C will be delivered via HIPEC (hyperthermic intraperitoneal chemotherapy).

Participants in this group will receive weight-based dosing of mitomycin C intra-operatively: 1) 9 mg/m2 at minute 0 and 2) 3.5 mg/m2 at minute 60 for total dose of 12.5 mg/m2. Mitomycin C will be delivered via HIPEC (hyperthermic intraperitoneal chemotherapy).

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT04779554

First Posted

February 27, 2021

Last Updated

March 9, 2023

Sponsor

Prakash Pandalai

1. Study Identification

Unique Protocol Identification Number

NCT04779554

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 4, 2021 (Actual)

Primary Completion Date

February 2024 (Anticipated)

Study Completion Date

February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Prakash Pandalai

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peritoneal Carcinomatosis

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Flat Dose Mitomycin C

Arm Type

Experimental

Arm Description

Arm Title

Weight-Based Mitomycin C

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Mitomycin C, flat dose 40 mg

Intervention Description

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 60.

Intervention Type

Drug

Intervention Name(s)

Mitomycin C, weight-based dose 12.5 mg/m2

Intervention Description

Mitomycin C will be delivered as heated intraperitoneal chemotherapy (HIPEC) in two weight-based doses of 9 mg/m2 at minute 0 and 3 mg/m2 at minute 60.

Primary Outcome Measure Information:

Title

Area Under the Curve (AUC) - Pharmacokinetics

Description

Time Frame

Approximately 20 hours

Title

Drug Clearance (CL) - Pharmacokinetics

Description

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.

Time Frame

Approximately 20 hours

Title

Drug Half-Life (T1/2) - Pharmacokinetics

Description

Time Frame

Approximately 20 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Prakash Pandalai, MD

Phone

859-323-8920

Prakash.Pandalai@uky.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Prakash Pandalai, MD

Organizational Affiliation

University of Kentucky

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Kentucky

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40536

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Prakash Pandalai, MD

Prakash.Pandalai@uky.edu

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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