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: Unknown

Duration: 2 years

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if HIPEC (a heated chemotherapy treatment applied directly inside the abdomen) can increase the protein PD-L1 in stomach cancer that has spread to the abdominal lining. Researchers seek to compare the effectiveness of this approach to regular chemotherapy administered through the bloodstream. The treatment involves two chemotherapy drugs, Cisplatin and Mitomycin. The trial seeks participants with stomach cancer and peritoneal metastases who have already received systemic chemotherapy for 2-4 months. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that using cisplatin and mitomycin in HIPEC, a heated chemotherapy method, is safe. Studies have examined the use of cisplatin during surgery to reduce the risk of cancer recurrence. In these studies, patients generally tolerated cisplatin well, though some experienced common chemotherapy side effects, such as nausea and reduced blood cell counts.

For mitomycin, research has also confirmed its safety in HIPEC. Results indicate it is generally safe, with side effects similar to those of cisplatin, including mild nausea and fatigue.

Both treatments have demonstrated safety when used in this manner, but side effects remain possible. Patients should discuss potential risks with their doctors before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using HIPEC (Hyperthermic Intraperitoneal Chemotherapy) with Cisplatin and Mitomycin for advanced stomach cancer because it offers a unique delivery approach. Unlike traditional chemotherapy, which is typically administered intravenously and circulates throughout the entire body, HIPEC delivers heated chemotherapy drugs directly into the abdominal cavity during surgery. This localized method allows for higher concentrations of the drugs to target cancer cells more effectively while minimizing systemic side effects. Additionally, the heat enhances the effectiveness of the chemotherapy, potentially improving outcomes for patients with advanced stomach cancer who have limited treatment options.

What evidence suggests that HIPEC is effective for advanced stomach cancer?

Studies have shown that using a heated chemotherapy treatment called HIPEC with the drug cisplatin can help reduce the recurrence of stomach cancer. Research also suggests that HIPEC with cisplatin might extend patients' lives. When combined with surgery, HIPEC has been linked to better survival rates compared to traditional chemotherapy that affects the whole body. In this trial, participants will receive HIPEC with either cisplatin or mitomycin. Studies indicate that mitomycin can potentially extend patients' lives when used in HIPEC for stomach cancer. Together, cisplatin and mitomycin in HIPEC have shown promise in treating advanced stomach cancer and may offer a survival benefit. ^{1 2 6 7 8}

Who Is on the Research Team?

Ardaman Shergill, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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 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]

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]

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According to several studies, CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC.

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sciencedirect.com

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HIPEC might improve survival when combined with cytoreductive surgery in advanced ovarian cancer. · Evidence supports the efficacy of HIPEC in interval debulking ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9714394/

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No adjuvant or neoadjuvant systemic chemotherapy was used in these studies and the 5-year overall survival (OS) ranges from 42 to 66% in the experimental groups ...

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This review explores the biology of gastric cancer peritoneal metastases and the benefits of bidirectional iterative IP chemotherapy.

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sciencedirect.com

sciencedirect.com/science/article/pii/S0748798325001593

Management of peritoneal gastric metastasis: An update

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bmccancer.biomedcentral.com

bmccancer.biomedcentral.com/articles/10.1186/s12885-021-08872-8

Preventive HIPEC in combination with perioperative FLOT ...

The scope of the trial is to evaluate the efficacy as well as the safety and tolerability of the combination of perioperative chemotherapy with ...