Chemotherapy Dosing Strategies for Peritoneal Carcinomatosis

Recruiting at 1 trial location

Overseen By Prakash Pandalai, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Prakash Pandalai

Must not be taking: Investigational agents

Disqualifiers: Extra-abdominal metastases, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two dosing methods of the chemotherapy drug Mitomycin C (also known as Mutamycin or Mitomycin) for treating peritoneal carcinomatosis, which is cancer spread in the abdominal area from certain gastrointestinal cancers. The goal is to determine if a weight-based dose is as effective as a flat dose but with fewer side effects. Participants will receive the drug during surgery using a method that heats the chemotherapy before applying it directly to the affected area. The trial seeks patients with specific types of abdominal cancer, such as colorectal cancer, who are eligible for surgery to remove visible tumors and have a life expectancy of more than three months. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy or radiotherapy within 4 weeks before joining the study. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using Mitomycin C in hyperthermic intraperitoneal chemotherapy (HIPEC) is generally safe and well-tolerated. In previous studies, patients who received HIPEC with Mitomycin C did not encounter more safety issues than those treated with alternatives like Oxaliplatin, indicating manageable risks.

One study found that patients experienced a significant decrease in their peritoneal cancer index, which measures cancer spread, when treated with Mitomycin C. This suggests the treatment is both effective and safe for cancer that has spread to the abdominal lining.

While all chemotherapy treatments carry some risks, evidence suggests that Mitomycin C via HIPEC is a reliable option for many patients. Patients should always discuss potential side effects and risks with their healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these chemotherapy dosing strategies for peritoneal carcinomatosis because they explore how different dosing methods can potentially improve outcomes. The trial investigates flat dosing versus weight-based dosing of mitomycin C, delivered intra-operatively via hyperthermic intraperitoneal chemotherapy (HIPEC). Unlike traditional systemic chemotherapy, HIPEC directly targets cancer cells in the abdomen, potentially enhancing drug absorption and effectiveness while minimizing systemic side effects. By comparing these two dosing strategies, researchers hope to discover which method provides better control of the cancer, paving the way for more personalized and effective treatment regimens.

What evidence suggests that this trial's treatments could be effective for peritoneal carcinomatosis?

This trial will compare two dosing strategies of Mitomycin C delivered via heated chemotherapy (HIPEC) for patients with cancer in the abdominal area. Research has shown that combining a specific type of surgery with heated chemotherapy can extend patients' lives. In one study, patients who received both the surgery and heated chemotherapy lived for an average of 11 months, compared to 6.5 months for those who only had the surgery. Other studies have reported even longer average survival times, between 30 and 41 months, for those who received both treatments. This suggests that heated chemotherapy, using the drug Mitomycin C, can effectively target cancer while reducing side effects. Participants in this trial will receive either a flat dose or a weight-based dose of Mitomycin C to evaluate the effectiveness of these dosing strategies. ^{3 6 7 8 9}

Who Is on the Research Team?

Prakash Pandalai, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for patients with specific abdominal cancers (like appendiceal cancer or colorectal cancer that has spread to the lining of the abdomen) who are fit enough for surgery and have a life expectancy over 3 months. They must understand and agree to the study's terms, have good organ function, and not be pregnant or breastfeeding. People with metastases outside the abdomen, recent chemotherapy or radiotherapy, ongoing severe illness, or allergies to similar drugs cannot join.

Inclusion Criteria

You are a suitable candidate for a surgery that aims to remove as much of the tumor as possible.

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

Exclusion Criteria

Any extra-abdominal metastases

Untreated lung metastases

Liver metastases not amenable to resection or ablation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cytoreductive Surgery and HIPEC

Participants undergo cytoreductive surgery followed by intra-operative administration of heated intra-peritoneal chemotherapy (HIPEC) with either flat dose or weight-based dose of Mitomycin C

1 day

1 visit (in-person, surgical procedure)

Immediate Post-operative Monitoring

Participants are monitored for pharmacokinetics of Mitomycin C, including drug clearance, area under the curve, and half-life

Approximately 20 hours

Continuous monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mitomycin C

Trial Overview The study is testing two ways of giving Mitomycin C during heated chemo after tumor-removing surgery: one based on patient weight (12.5 mg/m2) and another as a flat dose (40 mg). The goal is to see if weight-based dosing can effectively target peritoneal surfaces while reducing overall toxicity compared to flat dosing.

How Is the Trial Designed?

Group I: Weight-Based Mitomycin C Experimental Treatment 1 Intervention

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).

Group II: Flat Dose Mitomycin C Experimental Treatment 1 Intervention

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).

Mitomycin C is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Mitomycin C for:

• Stomach cancer
• Pancreatic cancer
• Peritoneal carcinomatosis (as part of HIPEC procedure)

Approved in European Union as Mitomycin C for:

• Stomach cancer
• Pancreatic cancer
• Peritoneal carcinomatosis (as part of HIPEC procedure)

Approved in Canada as Mitomycin C for:

• Stomach cancer
• Pancreatic cancer
• Peritoneal carcinomatosis (as part of HIPEC procedure)

Approved in Japan as Mitomycin C for:

• Stomach cancer
• Pancreatic cancer
• Peritoneal carcinomatosis (as part of HIPEC procedure)

Who Is Running the Clinical Trial?

Prakash Pandalai

Lead Sponsor

Trials

1

Recruited

100+

Published Research Related to This Trial

In a study of 28 patients with peritoneal carcinomatosis, intraperitoneal chemohyperthermic perfusion (ICHP) of mitomycin C (MMC) resulted in high concentrations of the drug in the peritoneal cavity while maintaining limited systemic exposure, suggesting a targeted approach to treatment.

The pharmacokinetics of MMC showed a mean maximum plasma concentration of 0.14 microg/ml and a low percentage of the dose recovered unchanged in urine (7.21%), indicating that ICHP effectively delivers the drug to the tumor site with reduced toxicity compared to systemic administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of mitomycin C after resection of peritoneal carcinomatosis and intraperitoneal chemohyperthermic perfusion. Cerretani, D., Nencini, C., Urso, R., et al.[2013]

Mitomycin-C (MMC) administered as a hyperthermic intraperitoneal lavage after surgery for advanced gastrointestinal cancer showed a significant absorption rate of about 70%, indicating effective drug delivery to the abdominal cavity.

The procedure had low morbidity primarily related to surgery, with mild to moderate myelosuppression as the main drug-related side effect, suggesting that this method of delivery is relatively safe and warrants further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically directed chemotherapy: heated intraperitoneal lavage with mitomycin C. Fernández-Trigo, V., Stuart, OA., Stephens, AD., et al.[2019]

In a study of 15 patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy, the extent of peritoneal resection (total vs. less-extensive) did not significantly impact the pharmacokinetics of mitomycin C and doxorubicin, indicating that drug absorption into the bloodstream was similar regardless of the surgical approach.

The results suggest that the pharmacological barrier between the peritoneal cavity and plasma is not solely dependent on the integrity of the peritoneum, which could have implications for optimizing chemotherapy delivery in patients with peritoneal carcinomatosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extent of parietal peritonectomy does not change intraperitoneal chemotherapy pharmacokinetics. de Lima Vazquez, V., Stuart, OA., Mohamed, F., et al.[2013]

In a study of 142 patients with gastrointestinal cancer treated with mitomycin C, 8.5% experienced renal toxicity, indicating a significant risk associated with this chemotherapy drug.

The risk of renal toxicity was found to be dose-related, with only 1.6% of patients receiving less than 50 mg/m2 developing toxicity, compared to 10.8% for those receiving 50 to 69 mg/m2 and 27.8% for those receiving more than 70 mg/m2, suggesting that a safer total dose is below 50 mg/m2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal complications of mitomycin C therapy with special reference to the total dose. Valavaara, R., Nordman, E.[2019]

In a study monitoring safety during hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC), no detectable MMC was found in air samples or in the plasma of surgeons, indicating a low risk of exposure.

The use of double latex gloves effectively prevented dermal exposure to MMC, supporting their safety in surgical settings during HIPEC procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigations on safety of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C. Schmid, K., Boettcher, MI., Pelz, JO., et al.[2013]

In a study of 314 patients undergoing heated intraperitoneal chemotherapy (HIPEC) with a fixed 40-mg dose of mitomycin C (MMC), the incidence of severe leukopenia and neutropenia was significantly lower than previously reported rates of 20-40% when dosing was based on weight or body surface area.

The findings suggest that routine prophylactic use of granulocyte-colony-stimulating factor (GCSF) is unnecessary for all patients, as only 7% developed severe leukopenia and 4.5% developed neutropenia, indicating that a fixed dose of MMC may reduce the risk of immunosuppression during HIPEC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated Intraperitoneal Chemotherapy with Mitomycin C. Feferman, Y., Bhagwandin, S., Kim, J., et al.[2018]

Intraperitoneal (IP) mitomycin C was administered to 14 patients with refractory peritoneal carcinomatosis (PC) from gynecologic cancers, showing minimal systemic toxicity and a manageable safety profile, although some experienced mild thrombocytopenia and abdominal pain due to chemical peritonitis.

Of the seven patients with measurable disease, six showed normalization of disease markers, and eight out of 14 patients remained alive without clinical evidence of disease after a median follow-up of 10 months, suggesting that IP mitomycin C could be an effective treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal mitomycin C in the treatment of peritoneal carcinomatosis following second-look surgery. Monk, BJ., Surwit, EA., Alberts, DS., et al.[2018]

Heated intraoperative intraperitoneal chemotherapy with mitomycin C (MMC) results in high concentrations of the drug in the peritoneal cavity while limiting systemic absorption, which suggests a targeted approach to treating peritoneal carcinomatosis.

Extensive peritoneal resections during surgery lead to increased systemic absorption of MMC, but the increase is minimal and unlikely to significantly raise the risk of systemic toxicity, indicating a favorable safety profile for this treatment method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heated intraoperative intraperitoneal mitomycin C and early postoperative intraperitoneal 5-fluorouracil: pharmacokinetic studies. Jacquet, P., Averbach, A., Stephens, AD., et al.[2022]

In a study of 45 patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer, neutropenia occurred in 40% of cases, indicating it is a common complication of this treatment.

The risk and severity of neutropenia were directly correlated with higher plasma concentrations of Mitomycin C (MMC) during HIPEC, suggesting that monitoring MMC levels, particularly at 30 minutes and 45 minutes after treatment, could help predict and manage neutropenia risk in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitomycin C Pharmacokinetics as Predictor of Severe Neutropenia in Hyperthermic Intraperitoneal Therapy. Kemmel, V., Mercoli, HA., Meyer, N., et al.[2022]

In a study comparing HIPEC with Oxaliplatin (39 patients) and Mitomycin C (MMC, 56 patients) for colorectal cancer peritoneal carcinomatosis, Oxaliplatin patients had a higher extent of disease but less intra-operative blood loss compared to MMC patients.

Despite differences in toxicity, including neutropenia in MMC patients, there was no significant difference in recurrence-free survival (RFS) or overall survival (OS) between the two treatment groups, suggesting that neither agent showed a clear advantage in long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. Hompes, D., D'Hoore, A., Wolthuis, A., et al.[2022]

In a study involving 14 athymic nude male rats, hyperthermic intraperitoneal chemotherapy (IPEC) using mitomycin C (MMC) showed high concentrations of the drug in the peritoneal and extraperitoneal tissues, indicating effective localized treatment.

The study found that increasing the temperature to 41°C during IPEC did not significantly alter the pharmacokinetics of MMC compared to normothermic conditions, suggesting that hyperthermia does not enhance the drug's absorption or effectiveness in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of hyperthermia on pharmacokinetics of intraperitoneal mitomycin C in rats investigated by microdialysis. Sørensen, O., Andersen, AM., Kristian, A., et al.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3087875/

Final Results of a Phase III Randomized Clinical Trial The median survival was 6.5 months (95% confidence interval 4.8–8.2 months) in CRS and 11.0 months (95% confidence interval 10.0–11.9 months) in the CRS + HIPEC ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12317892/

Great Debate: Hyperthermic Intraperitoneal Chemotherapy for ... Notably, while not directly comparable, the published data for CRS-HIPEC consistently reported higher median survival 30–41 months compared with ...

3. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2804110

Efficacy and Safety of Intraoperative Hyperthermic ... Results from randomized clinical trials (RCTs) have yielded mixed results regarding the clinical efficacy of HIPEC.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03073694?term=AREA%5BInterventionSearch%5D(MUTAMYCIN)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=8

Comparing Cytoreductive Surgery and Hyperthermic ... In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1015958424024886

Hyperthermic intraperitoneal chemotherapy: Ideal and reality Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) is a new adjuvant therapy for the treatment of abdominal malignant tumors and metastases, which has shown ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7705102/

Clinical Efficacy and Safety of Hyperthermic Intraperitoneal ... CRC patients at high risk of PC who proactively underwent HIPEC treatment showed a significantly reduced peritoneal metastasis rate (RR: 0.41, 95% CI: 0.21–0.83 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02040142

Study Details | HIPEC for Peritoneal Carcinomatosis This is a clinical study investigating the new treatment of surgery combined with intraperitoneal mitomycin-C for patients with gastrointestinal cancer that ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0748798325005086

The Mitomycin versus Oxaliplatin debate on HIPEC in ... Our systematic review and meta-analysis found no significant difference in survival outcomes or postoperative morbidity between MMC and Oxaliplatin-based HIPEC.

9. cancernetwork.com cancernetwork.com/view/pipac-mmc-plus-folfiri-shows-feasibility-safety-in-peritoneal-metastases

PIPAC-MMC Plus FOLFIRI Shows Feasibility, Safety in ... A reduction in peritoneal cancer index (PCI) was observed in 84% of this patient group, with an average PIPAC1 to PIPAC3 reduction of 53%. Of ...