What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as oxaliplatin and fluoropyrimidines (5-fluorouracil and capecitabine), are associated with side effects including neutropenia, infection, diarrhea, fatigue, and neuropathy. Specifically, oxaliplatin can cause cumulative sensory neuropathy, while capecitabine is known for causing hand-foot syndrome and gastrointestinal issues like diarrhea and nausea. Mitomycin C, especially when used in hyperthermic intraperitoneal chemotherapy (HIPEC), can lead to hematologic toxicities such as neutropenia and anemia, as well as non-hematologic toxicities like fatigue, dehydration, and gastrointestinal disturbances. These side effects necessitate careful monitoring and management during treatment.

What prior FDA approvals exist?

The FDA has approved several chemotherapy agents for the treatment of colorectal cancer, including fluoropyrimidines (such as 5-fluorouracil and capecitabine), oxaliplatin, and irinotecan. These agents are often used in combination regimens like FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI (5-fluorouracil, leucovorin, and irinotecan). Additionally, targeted therapies such as bevacizumab (an anti-VEGF antibody) and cetuximab (an anti-EGFR antibody) have been approved for use in specific patient populations. While hyperthermic intraperitoneal chemotherapy (HIPEC) with agents like mitomycin C is being studied for its enhanced cytotoxic effects through hyperthermia, it is not yet a standard FDA-approved treatment for colorectal cancer.

What other types of research exist?

Promising novel alternatives to Heated Mitomycin C for colorectal cancer patients include: 1) Immunotherapy with immune checkpoint inhibitors such as pembrolizumab or nivolumab, especially for patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. 2) Targeted therapies like bevacizumab (anti-VEGF) or cetuximab (anti-EGFR) in combination with chemotherapy. 3) Combination regimens such as FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). 4) Investigational therapies including CAR-T cell therapy and novel agents in clinical trials. Patients should discuss these options with their oncologist to determine the best individualized treatment plan.

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Chemotherapy +/− Surgery + Mitomycin C for Colorectal Cancer

Q: What is the mechanism of action of this treatment?

Common treatments for colorectal cancer include chemotherapy agents like fluorouracil (5-FU) and oxaliplatin, which disrupt DNA replication and repair, causing cancer cell death. Hyperthermia, or the application of heat, can enhance these effects by increasing drug uptake and cancer cell sensitivity. Heated mitomycin C leverages this by using heat to boost the drug's cytotoxicity, potentially improving treatment efficacy and patient outcomes.

Phase 3

Waitlist Available

Led By Alexander Stojadinovic, MD

Research Sponsored by Walter Reed Army Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically confirmed colon adenocarcinoma meeting the following criteria: Newly diagnosed disease, Advanced disease, Confirmed synchronous or metachronous limited peritoneal disease dissemination, Disease not appendiceal or rectal cancer, Disease not signet ring cell type, Disease amenable to complete cytoreduction surgery with specific criteria, ECOG performance status 0-1, ANC > 1,200/mm³, WBC > 4,000/mm³, Platelet count 150,000/mm³, INR ≤ 1.5, Total serum bilirubin ≤ 1.5 mg/dL (> 1.5 mg/dL for patients with Gilbert syndrome), Alkaline phosphatase < 2.5 times upper limit of normal, AST < 1.5 times ULN, Serum creatinine normal, BUN normal, Not pregnant or nursing, Fertile patients must use effective contraception, Patients who are status post-revascularization procedures with satisfactory cardiac function, No acute myocardial infarction within the past 6 months, No significant history of a medical problem or co-morbidity that would preclude a major abdominal operation, No concurrent second malignancy requiring systemic therapy, No psychiatric or addictive disorders, or other conditions that would preclude the patient from meeting the study requirements, Patients who received prior adjuvant therapy for colon adenocarcinoma and/or prior first-line systemic therapy for metastatic colon adenocarcinoma are eligible

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Approved for 5 Other Conditions

Pivotal Trial

No Placebo-Only Group

All Individual Drugs Already Approved

Summary

This trial is testing whether using a warmed-up chemotherapy drug called mitomycin C after surgery can help kill leftover cancer cells in patients with advanced colon cancer that has spread to the abdomen. The goal is to see if this approach improves survival and quality of life. Mitomycin C has historically been used in the treatment of intraperitoneal carcinomatosis from colon cancer.

Who is the study for?

This trial is for adults with newly diagnosed colon cancer that has spread to the lining of the abdomen but not beyond. They must be fit for major surgery, have a Peritoneal Cancer Index score ≤20, normal organ function tests, and no severe heart or lung conditions. Pregnant women are excluded and participants must use effective contraception.

What is being tested?

The study is testing if standard chemotherapy treatments for colon cancer work better when combined with surgery and heated mitomycin C (a type of chemotherapy). Patients will be randomly assigned to receive either just the standard therapy or the combination with surgery and mitomycin C.

What are the potential side effects?

Chemotherapy drugs like capecitabine, fluorouracil, cetuximab may cause nausea, vomiting, diarrhea, mouth sores; while mitomycin C can lead to tiredness and more serious blood-related side effects. Surgery carries risks such as infection and bleeding.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm IIExperimental Treatment11 Interventions

Patients undergo cytoreduction surgery and hyperthermic intraperitoneal mitomycin C over 45-90 minutes. Beginning 8 weeks after surgery, patients receive standard systemic therapy as in arm I. Treatment with systemic therapy repeats for 6 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm IActive Control9 Interventions

Patients receive standard systemic therapy, at the discretion of patients' oncologist, comprising combinations of fluorouracil, leucovorin calcium, irinotecan hydrochloride, oxaliplatin, and/or capecitabine (including FOLFOX4, mFOLFOX6, CapeOx, or FOLFIRI), bevacizumab, or cetuximab. Treatment repeats in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may crossover to arm II.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bevacizumab

FDA approved

Cetuximab

FDA approved

Fluorouracil

FDA approved

FOLFOX regimen

2009

Completed Phase 3

~2440

Capecitabine

FDA approved

Fluorouracil

FDA approved

Irinotecan

FDA approved

Leucovorin

FDA approved

Mitomycin

FDA approved

Oxaliplatin

FDA approved

therapeutic conventional surgery

2003

Completed Phase 3

~12900

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for colorectal cancer include chemotherapy agents like fluorouracil (5-FU) and oxaliplatin, which disrupt DNA replication and repair, causing cancer cell death. Hyperthermia, or the application of heat, can enhance these effects by increasing drug uptake and cancer cell sensitivity. Heated mitomycin C leverages this by using heat to boost the drug's cytotoxicity, potentially improving treatment efficacy and patient outcomes.

The Treatment of Heterotopic Human Colon Xenograft Tumors in Mice with 5-Fluorouracil Attached to Magnetic Nanoparticles in Combination with Magnetic Hyperthermia Is More Efficient than Either Therapy Alone.Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial.