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

Prakash Pandalai

Status and phase: Enrolling; Phase 2

Conditions: Peritoneal Carcinomatosis

Treatments: Drug: Mitomycin C, flat dose 40 mg; Drug: Mitomycin C, weight-based dose 12.5 mg/m2

Study type: Interventional

Funder types: Other

Identifiers

NCT04779554

MCC-20-GI-115

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Flat Dose Mitomycin C

Experimental group

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).

Treatment:

Drug: Mitomycin C, flat dose 40 mg

Weight-Based Mitomycin C

Experimental group

Description:

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).

Treatment:

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