HIPEC for Advanced Stomach Cancer

Overseen By Cancer Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Investigational agents

Disqualifiers: Untreated neoplasm, Visceral 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

Compensation: Varies

Number of Visits: 0

Duration: 2 years

21 Participants Needed

Trial Summary

What is the purpose of this trial?

To assess if PD-L1 expression can be upregulated in peritoneal metastases from gastric cancer after the administration of HIPEC with greater frequency compared to systemic chemotherapy alone

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on any investigational drugs, you may need to stop them to participate in this trial.

What data supports the effectiveness of the drug combination used in HIPEC for advanced stomach cancer?

Research shows that using cisplatin and mitomycin C in combination with other drugs like 5-fluorouracil can be effective in treating advanced gastric cancer. Studies have found that these drugs, when used together, can improve treatment outcomes and are generally safe for patients. ^{1 2 3 4 5}

Is HIPEC with cisplatin and mitomycin C safe for humans?

HIPEC with cisplatin and mitomycin C has been studied for safety in various cancers. Common side effects include nausea, vomiting, and kidney issues, with some patients experiencing more serious effects like kidney injury and anemia at higher doses. Overall, it has an acceptable safety profile when used at recommended doses. ^{3 6 7 8 9}

What makes the HIPEC treatment with Cisplatin and Mitomycin unique for advanced stomach cancer?

HIPEC (Hyperthermic Intraperitoneal Chemotherapy) with Cisplatin and Mitomycin is unique because it involves directly applying heated chemotherapy drugs into the abdominal cavity, which can enhance the effectiveness of the drugs against cancer cells in the peritoneal area. This method is different from standard chemotherapy, which is usually administered intravenously and affects the whole body. ^{2 4 10 11 12}

Research Team

Ardaman Shergill, MD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for adults over 18 with advanced gastric cancer that has spread to the lining of the abdomen. They must have completed at least 2-4 months of chemotherapy, have good kidney and liver function, not be severely ill from other causes, and cannot be pregnant or breastfeeding. People with HIV or hepatitis are eligible if their viral loads are undetectable.

Inclusion Criteria

platelets ≥100,000/mcL

I have another cancer, but it won't affect this trial's treatment.

absolute neutrophil count ≥1,500/mcL

Exclusion Criteria

I am allergic to medications similar to cisplatin or Mitomycin C.

You cannot be part of any other experimental treatments or studies at the same time.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) to assess PD-L1 expression in peritoneal metastases

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including perioperative morbidity and mortality at 30 days

30 days

Long-term follow-up

Participants are monitored for overall survival and changes in peritoneal cancer index (PCI) over 2 years

2 years

Treatment Details

Interventions

• Cisplatin
• Mitomycin

Trial Overview The study tests whether heating chemotherapy drugs (Cisplatin and Mitomycin) inside the abdomen after surgery can make immune markers go up in stomach cancer cells more than just giving chemo through a vein. This technique is called HIPEC.

Participant Groups

Group I: Drug Administration Period Experimental Treatment 2 Interventions

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

In a study involving 56 patients with inoperable advanced gastric cancer, a higher dose of cisplatin (80 mg/m²) resulted in a significantly better response rate (56.3%) compared to a lower dose (60 mg/m²) which had a response rate of only 18.9%.

Both treatment regimens showed similar safety profiles with manageable side effects like myelosuppression and gastrointestinal symptoms, indicating that the higher dose of cisplatin is effective without increasing serious adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with cisplatin, 5'-deoxy-5-fluorouridine (5'-DFUR) and mitomycin (MMC) in patients with inoperable, advanced gastric cancer. Koizumi, W., Kurihara, M., Hasegawa, K., et al.[2019]

The study identified an effective combination of 5-fluorouracil (5-FU), cisplatin (CDDP), and mitomycin C (MMC) for hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced gastric cancer, showing significant tumor growth inhibition in vitro.

5-FU demonstrated a concentration-dependent growth-inhibitory effect and enhanced efficacy under hyperthermic conditions (42°C), suggesting that a 30-minute exposure at specific drug concentrations (5-FU at 200 µg/mL, CDDP at 10 µg/mL, MMC at 2 µg/mL) is optimal for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-fluorouracil combined with cisplatin and mitomycin C as an optimized regimen for hyperthermic intraperitoneal chemotherapy in gastric cancer. Murata, S., Yamamoto, H., Shimizu, T., et al.[2018]

In a study involving 12 patients with advanced gastric cancer, the combination of hyperthermic intraperitoneal chemotherapy (HIPEC) using 5-fluorouracil (5-FU), mitomycin C (MMC), and cisplatin (CDDP) was found to be safe, with a recommended dose of 1000 mg of 5-FU.

The treatment showed promising efficacy, with 66.7% of patients experiencing no recurrence of peritoneal metastases and an impressive 5-year overall survival rate of 83.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and safety of hyperthermic intraperitoneal chemotherapy using 5-fluorouracil combined with cisplatin and mitomycin C in patients undergoing gastrectomy for advanced gastric cancer. Murata, S., Yamamoto, H., Naitoh, H., et al.[2018]

Combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improves the prognosis for patients with diffuse malignant peritoneal mesothelioma (DMPM), as shown in a systematic review of 28 studies.

Cisplatin is identified as the key drug for HIPEC, often used in combination with doxorubicin, and this bi-drug regimen has been associated with better long-term outcomes, making it the most recommended protocol in international guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peritoneal Mesothelioma: Systematic Review of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Protocol Outcomes. Kepenekian, V., Sgarbura, O., Marchal, F., et al.[2023]

The optimal chemotherapeutic regimen for hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients is still undetermined, highlighting the need for further research.

Variability in study parameters, such as drug combinations, dosages, and perfusion techniques, suggests that a combination of drugs may enhance treatment efficacy, but more clinical studies are necessary to establish the best approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer. Braam, HJ., Schellens, JH., Boot, H., et al.[2016]

Cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) at a dose of 100 mg/m² is safe and well-tolerated in patients with platinum-sensitive recurrent epithelial ovarian cancer, with only one out of six patients experiencing significant toxicity.

The study demonstrated favorable pharmacokinetics, with a mean peritoneal-to-plasma AUC ratio of 19.5, and confirmed the presence of cisplatin-induced DNA adducts in tumor samples, suggesting potential efficacy for HIPEC as a complementary treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer. Zivanovic, O., Abramian, A., Kullmann, M., et al.[2019]

The maximum tolerated dose (MTD) of hyperthermic intraperitoneal cisplatin at 43°C for gynecological cancer patients was determined to be 85 mg/m2, based on a Phase I trial involving 30 patients.

Common adverse effects included nausea and vomiting in all patients, with significant risks of kidney injury and other dose-limiting toxicities observed at the highest dose level, indicating the need for careful monitoring of renal function during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Dose-Finding Trial for Hyperthermic Intraperitoneal Cisplatin in Gynecological Cancer Patients Receiving Hyperthermic Intraperitoneal Chemotherapy. Chan, CY., Li, H., Wu, MF., et al.[2021]

In a Phase I study involving 40 patients with urologic and gynecologic cancers, cis-diamminedichloroplatinum(II) (CIS-DDP) was found to have manageable side effects, primarily nausea, vomiting, and anorexia, which resolved quickly after stopping the treatment.

The study indicated low levels of hematopoietic and renal toxicities, with no reported cases of hearing disturbances or tinnitus, suggesting a favorable safety profile for CIS-DDP at doses of 50 mg/m2 for single administration and 20 mg/m2/day for five consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

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]

Prophylactic HIPEC with cisplatin after radical gastrectomy for locally advanced gastric cancer did not increase the incidence of postoperative complications, indicating it is a safe procedure.

While HIPEC did not significantly reduce the risk of peritoneal recurrence compared to standard chemotherapy alone, it did result in a lower percentage of patients with elevated tumor markers, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer after curative surgery. Fan, B., Bu, Z., Zhang, J., et al.[2021]

A systematic review of 42 studies involving 1325 patients found that hyperthermic intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery (CRS) shows promising results for treating peritoneal metastasis in gastric cancer, particularly with a regimen of cisplatin and mitomycin C.

Studies indicated that performing HIPEC after gastrointestinal anastomosis resulted in lower rates of anastomotic leakage, and those using an open HIPEC approach with a two-drug regimen reported better overall survival rates, highlighting the importance of technique in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIPEC in Peritoneal Metastasis of Gastric Origin: A Systematic Review of Regimens and Techniques. Gronau, F., Feldbruegge, L., Oberwittler, F., et al.[2022]

In a study of 63 patients undergoing cisplatin (CDDP)-containing hyperthermic intraperitoneal chemotherapy (HIPEC), 66.1% experienced acute kidney injury (AKI), with the extent of parietal peritonectomy being a significant predictor of this complication.

Preclinical rat models showed that bilateral anterior parietal peritonectomy increased systemic absorption of CDDP by 1.6 to 2-fold, suggesting that careful consideration of CDDP dosage and concentration is crucial to minimize systemic toxicity and AKI risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury. Liesenfeld, LF., Quiring, E., Al-Saeedi, M., et al.[2023]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Combination therapy with cisplatin, 5'-deoxy-5-fluorouridine (5'-DFUR) and mitomycin (MMC) in patients with inoperable, advanced gastric cancer. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

5-fluorouracil combined with cisplatin and mitomycin C as an optimized regimen for hyperthermic intraperitoneal chemotherapy in gastric cancer. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Feasibility and safety of hyperthermic intraperitoneal chemotherapy using 5-fluorouracil combined with cisplatin and mitomycin C in patients undergoing gastrectomy for advanced gastric cancer. [2018]

4. India pubmed.ncbi.nlm.nih.gov

Peritoneal Mesothelioma: Systematic Review of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Protocol Outcomes. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Dose-Finding Trial for Hyperthermic Intraperitoneal Cisplatin in Gynecological Cancer Patients Receiving Hyperthermic Intraperitoneal Chemotherapy. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Investigations on safety of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Phase II trial of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer after curative surgery. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

HIPEC in Peritoneal Metastasis of Gastric Origin: A Systematic Review of Regimens and Techniques. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury. [2023]