Chemotherapy Dosing Strategies for Peritoneal Carcinomatosis
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Prakash Pandalai
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 4 jurisdictions
Trial Summary
What is the purpose of this trial?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.
Is Mitomycin C generally safe for humans?
Mitomycin C can cause kidney problems, especially at higher doses, and some patients may experience a drop in white blood cells, which can lead to infections. Safety concerns are often related to the dose and method of administration.
2781011Will 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.
How is the drug Mitomycin C used in treating peritoneal carcinomatosis unique?
Mitomycin C is unique in treating peritoneal carcinomatosis because it is administered directly into the abdominal cavity using a heated solution, which helps concentrate the drug at the tumor site while minimizing side effects throughout the body.
13689What data supports the effectiveness of the drug Mitomycin C for treating peritoneal carcinomatosis?
Research shows that Mitomycin C, when used in a heated form directly in the abdomen, can reach high concentrations in the tumor area with limited side effects, making it a potentially effective treatment for peritoneal carcinomatosis. In a study, 8 out of 14 patients treated with this method remained alive without signs of disease after 10 months.
14568Eligibility Criteria
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.Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Weight-Based Mitomycin CExperimental Treatment1 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 CExperimental Treatment1 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)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of Vermont Medical CenterBurlington, VT
University of KentuckyLexington, KY
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Who is running the clinical trial?
Prakash PandalaiLead Sponsor
References
Intraperitoneal mitomycin C in the treatment of peritoneal carcinomatosis following second-look surgery. [2018]Persistent or recurrent peritoneal carcinomatosis (PC) documented at second-look surgery has proved relatively refractory to second-line therapy. The majority of these tumors do not respond to cisplatin based chemotherapy. Because of the relatively high response rate we observed with systemically administered mitomycin C plus 5-fluorouracil, we initiated a trial of intraperitoneal (IP) mitomycin C (10 mg/m2 in 2 L dialysate fluid every 4 weeks) in 14 patients with refractory PC secondary to gynecologic malignancies. All but one patient had PC secondary to ovarian cancer documented at second-look cytoreductive surgery following intense cisplatin based drug therapy. One patient had endometrial cancer and had been treated previously with radiation. In all, 49 courses of intraperitoneal mitomycin C were administered to 14 patients. Systemic toxicity was minimal, except for mild thrombocytopenia that occurred in four patients. However, abdominal pain due to chemical peritonitis was cumulative and dose limiting after three to five courses of therapy. Of the seven patients with measurable disease (positive serum CA-125 or intraperitoneal cytology), six had normalization of at least one of these two parameters. Eight of the 14 patients remain alive without clinical evidence of disease with a median follow-up duration of 10 months. We conclude that IP mitomycin C is a well-tolerated and potentially effective treatment modality in patients with limited PC following second-look surgical debulking for gynecologic malignancy.
Renal complications of mitomycin C therapy with special reference to the total dose. [2019]One hundred forty-two patients with gastrointestinal cancer were treated with combination chemotherapy containing mitomycin C. The mitomycin C dose was less than or equal to 15 mg/m2 every 53rd day and the total cumulative dose was between 25 and 250 mg. Ten of the evaluable 118 patients (8.5%) developed renal toxicity due to mitomycin C. Five of these ten patients had microangiopathic hemolytic anemia, too. Six of them died 2 to 4.5 months after the last mitomycin C dose and four are alive 14 to 30 months after the last dose. Only 1 of the 63 patients (1.6%) who received less than 50 mg/m2 mitomycin C developed renal toxicity. Four of the 37 patients (10.8%) who received 50 to 69 mg/m2 and 5 of 18 (27.8%) who received more than 70 mg/m2 of mitomycin C developed nephrotoxicity. The toxicity of mitomycin C seems to be dose related, the safe total dose being less than 50 mg/m2 if delivered in doses of 10 to 15 mg/m2 at 8-week intervals.
Surgically directed chemotherapy: heated intraperitoneal lavage with mitomycin C. [2019]This chapter reported the pharmacokinetics and the toxicities of mitomycin-c (MMC) when administered as a hyperthermic intraperitoneal lavage after surgical resection of advanced primary or recurrent gastrointestinal cancer. Pharmacologic studies were performed in 10 patients and all adverse reactions were recorded in 20 patients. These 20 patients had advanced gastrointestinal malignancies with peritoneal carcinomatosis and underwent cytoreductive surgery prior to intraperitoneal lavage. Heated (42 degrees C) intraperitoneal mitomycin C was used in a lavage technique with 30 mg/3 1 of drug for 2 hours. The fluid was distributed throughout the abdominal cavity by vigorous external massage of the abdominal wall. This resulted in approximately 70 percent (21 mg) drug absorption from the perfusate. Urine output of MMC averaged 2.5 mg during the 2 hour procedure. Median peak blood levels of 0.25 micrograms/ml (range 0.11-0.41 micrograms/ml) were observed at 45-60 minutes into the procedure. Morbidity was low and was mainly related to the surgical procedures (prolonged ileus, postoperative fistulas) with mild to moderate drug-related myelosuppression. This new method of delivery of MMC and 5-FU should be explored in phase II clinical trials.
Heated intraoperative intraperitoneal mitomycin C and early postoperative intraperitoneal 5-fluorouracil: pharmacokinetic studies. [2022]The purpose of this study was to report the pharmacokinetics of heated intraoperative intraperitoneal mitomycin C (MMC) and to analyze the impact of heat, extent of peritoneal resections, and effect of intraoperative hyperthermic chemotherapy on the pharmacological properties of the peritoneal plasma barrier.
Extent of parietal peritonectomy does not change intraperitoneal chemotherapy pharmacokinetics. [2013]To measure the clearance intraperitoneal mitomycin C and doxorubicin in patients having peritonectomy and analyze the impact of the extent of peritoneal resection on pharmacokinetics.
Pharmacokinetics of mitomycin C after resection of peritoneal carcinomatosis and intraperitoneal chemohyperthermic perfusion. [2013]Over the last few years surgery on patients with abdominal malignancies has become more aggressive but the majority of patients present locoregional recurrence as peritoneal dissemination. Cytoreductive surgery followed by intraperitoneal chemohyperthermic perfusion (ICHP) has been described for treatment and prevention of locoregional cancer spread from various origins. This paper reports our study of the pharmacokinetics of mitomycin C (MMC) administered by intraperitoneal chemohyperthermic perfusion (ICHP) in patients with peritoneal carcinomatosis. 28 patients received MMC 20 mg/m2 intraperitoneally as a perfusion over 60 min. MMC was determined in perfusate, plasma and urine samples with a UV-HPLC method. A compartmental model was used to fit the drug concentrations in plasma and perfusate. Our results showed a mean maximum plasma concentration (Cmax) of 0.14 +/- 0.086 microg/ml with a peak time (Tmax) of 48..7 +/- 5.61 min. The mean area under the curve (AUC) and terminal half-life (t1/2) were 15.8 +/- 9.8 mg x min/L and 83.7 +/- 31.74 min respectively. Clearance (CL) was estimated by fitting the data by a compartmental model and the mean value was 72 +/- 66 L/h. The percent of the dose absorbed was very variable and ranged between 14 and 57% (mean 37 +/- 14%). The mean percentage of dose recovered unchanged in the urine during 24 hours was 7.21 +/- 3.73%. We conclude that ICHP in patients with peritoneal surface malignancies seems to have clinical value since it gives high peritoneal and tumor MMC concentrations with limited systemic exposure and toxicity.
Investigations on safety of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C. [2013]Previous safety monitoring of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC) did not demonstrate any detectable safety hazard to the personnel. Nevertheless, those results have been discussed controversially because of the methodological problems employed in the evaluation of potential exposure. We re-evaluated possible safety hazards of HIPEC by applying different monitoring strategies.
Impact of hyperthermia on pharmacokinetics of intraperitoneal mitomycin C in rats investigated by microdialysis. [2014]Patients with peritoneal surface malignancies are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, commonly using mitomycin C (MMC). The purpose of this study was to investigate impact of hyperthermia on pharmacokinetics of intraperitoneal MMC.
The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. [2022]Oxaliplatin and Mitomycin C (MMC) are both suitable as intraperitoneal chemotherapy agents in HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer (CRC).
Mitomycin C Pharmacokinetics as Predictor of Severe Neutropenia in Hyperthermic Intraperitoneal Therapy. [2022]Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an approach to overcome peritoneal carcinomatosis from colorectal adenocarcinoma. Mitomycin C (MMC) is frequently used but not devoid of toxicity, of which the most common and feared is neutropenia. Our study explores the clinical and surgical risk factors of neutropenia and a possible link between MMC pharmacokinetics and neutropenia as HIPEC's supervention.
Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated Intraperitoneal Chemotherapy with Mitomycin C. [2018]During heated intraperitoneal chemotherapy (HIPEC), neutropenia rates of 20 to 40% have been reported when mitomycin C (MMC) is dosed by weight or body surface area (BSA). This study investigated the authors' HIPEC experience using a fixed 40-mg dose of MMC, per consensus guidelines, and analyzed predictors for severe leukopenia and neutropenia.