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

Sponsor

Prakash Pandalai (Other)

Overall Status

Recruiting

CT.gov ID

NCT04779554

Collaborator

(none)

100

Enrollment

Location

Arms

35.1

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Peritoneal Carcinomatosis	Drug: Mitomycin C, flat dose 40 mg Drug: Mitomycin C, weight-based dose 12.5 mg/m2	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 28, 2021

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Flat Dose Mitomycin C 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).	Drug: Mitomycin 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 60.
Experimental: Weight-Based Mitomycin C 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).	Drug: Mitomycin 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 mg/m2 at minute 0 and 3 mg/m2 at minute 60.

Arm

Intervention/Treatment

Experimental: Flat Dose Mitomycin C

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).

Drug: Mitomycin 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 60.

Experimental: Weight-Based Mitomycin C

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).

Drug: Mitomycin 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 mg/m2 at minute 0 and 3 mg/m2 at minute 60.

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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