HIPEC for Gallbladder Cancer

Overseen By Brian Boone, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: West Virginia University

Must not be taking: Investigational agents

Disqualifiers: Metastatic disease, Hepatitis B/C, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: During procedure

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for gallbladder cancer using heated chemotherapy directly in the abdomen, known as HIPEC (Hyperthermic Intraperitoneal Chemotherapy). The researchers aim to determine if this method can safely benefit individuals at high risk of cancer spreading within the abdomen. Suitable candidates have confirmed gallbladder cancer and may have experienced a bile leak during surgery or have a tumor growing through the gallbladder wall. This approach could significantly improve outcomes for patients facing this challenging cancer type. As an Early Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are receiving any other investigational agents or have had prior systemic therapy for gallbladder adenocarcinoma, you would not be eligible to participate.

What prior data suggests that HIPEC is safe for gallbladder cancer patients?

Research has shown that HIPEC, or Heated Intra-Peritoneal Chemotherapy, is usually well-tolerated by patients. In one study, researchers used HIPEC after extensive surgery for gallbladder cancer and found it to be safe, with no major complications. Another study found that patients who received HIPEC along with surgery lived longer.

These results suggest that HIPEC might be a promising option for people at high risk of cancer spreading. However, this trial is in an early stage, meaning researchers are still learning about its safety and effectiveness in this specific situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for gallbladder cancer?

HIPEC is unique because it delivers chemotherapy directly to the abdominal cavity while the body is heated to 42°C. This method allows high concentrations of chemotherapy, specifically mitomycin C, to target cancer cells more effectively than traditional systemic chemotherapy. Researchers are excited about HIPEC's potential to improve drug absorption and target cancer cells more precisely, offering hope for better outcomes in gallbladder cancer treatment.

What evidence suggests that HIPEC might be an effective treatment for gallbladder cancer?

Research has shown that HIPEC, or Heated Intraperitoneal Chemotherapy, may help treat gallbladder cancer, especially when it spreads to the abdominal lining. This trial will evaluate HIPEC as a treatment option. Studies have found that combining HIPEC with surgery can improve survival rates, particularly in advanced or recurrent cases. For instance, one study found that patients who received HIPEC had a 2-year survival rate of over 26%, compared to just 17% for those who did not. HIPEC delivers heated chemotherapy directly into the abdomen, potentially making the treatment more effective and reducing side effects compared to traditional methods. These findings suggest that HIPEC might offer a significant survival benefit for patients facing this challenging cancer. ^{1 3 4 5 6}

Who Is on the Research Team?

Brian Boone, MD

Principal Investigator

WVU Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with high-risk gallbladder adenocarcinoma who've had bile spillage during surgery or have advanced tumors. They must have certain blood cell counts, normal organ function, no prior systemic therapy for this cancer, and not be pregnant or breastfeeding. Patients should be physically able to undergo additional surgery and agree to the study's terms.

Inclusion Criteria

ALT (SGPT) ≤ 2.5 X institutional upper limit of normal

My organ and bone marrow functions are normal.

Total bilirubin within normal institutional limits

Exclusion Criteria

You are currently taking any other experimental medications.

I have a blockage in my bile ducts thought to be caused by cancer, possibly needing a stent.

My cancer has spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo prophylactic Heated Intra-peritoneal Chemotherapy (HIPEC) with mitomycin C

During procedure

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for intraoperative complications, postoperative morbidity and mortality, length of stay, and readmission

90 days

Follow-up

Participants are monitored for peritoneal metastases and disease-free survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• HIPEC

Trial Overview The trial tests the safety of HIPEC (heated chemotherapy delivered directly into the abdomen) as a preventive treatment against peritoneal recurrence in gallbladder cancer after surgery. It measures complications, recovery time, and any postoperative issues compared to past data.

How Is the Trial Designed?

Group I: HIPEC Experimental Treatment 1 Intervention

Prophylactic Heated Intra-peritoneal Chemotherapy (HIPEC) 30 mg of mitomycin C (MMC) over the first 60 minutes followed by 10 mg over an additional 30 minutes. Perfusate will be heated to obtain a tissue temperature of 42°.

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

Approved in United States as HIPEC for:

• Peritoneal metastases from ovarian, stomach, colorectal, and appendiceal cancers
• Gallbladder adenocarcinoma with high risk of peritoneal recurrence

Approved in European Union as HIPEC for:

• Peritoneal metastases from ovarian, stomach, colorectal, and appendiceal cancers
• Malignant peritoneal mesothelioma

Approved in Canada as HIPEC for:

• Peritoneal metastases from ovarian, stomach, colorectal, and appendiceal cancers

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

Published Research Related to This Trial

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) is safe for high-risk patients with a peritoneal carcinomatosis index (PCI) of 0, showing no perioperative mortalities and a complication rate of 43% among 37 patients studied over a median follow-up of 5.2 years.

The treatment is associated with favorable long-term outcomes, with a 5-year recurrence-free survival (RFS) of 77% and overall survival (OS) of 100%, indicating its potential effectiveness in preventing disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for patients at High-Risk of Peritoneal Metastases. Morris, MC., Dhar, VK., Stevenson, MA., et al.[2020]

A review of current literature indicates that hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery significantly improves overall survival in ovarian cancer patients, with no significant increase in severe complications compared to surgery alone.

There is emerging evidence supporting the efficacy of HIPEC in treating uterine sarcoma with peritoneal sarcomatosis, suggesting it could be a promising new treatment strategy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic intraperitoneal chemotherapy (HIPEC) for gynecological cancer. Tsuyoshi, H., Inoue, D., Kurokawa, T., et al.[2021]

Hyperthermic intraperitoneal chemotherapy (HIPEC) enhances the effectiveness of chemotherapy in heat-sensitive ovarian cancer cells by disrupting DNA damage repair mechanisms, as shown by the identification of 349 differentially expressed proteins in a study using mass spectrometry on the A2780 cell line.

The protein RBL1 was significantly upregulated in cells treated with both hyperthermia and chemotherapy, suggesting it may play a crucial role in the enhanced sensitivity of these cells to chemotherapeutic drugs, making it a potential target for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermia enhances the efficacy of chemotherapeutic drugs in heat-sensitive cells through interfering with DNA damage repair. Ni, LP., Sun, HT., Wang, P., et al.[2022]

In a study using a rat model, hyperthermic intra-peritoneal perfusion of cisplatin did not enhance drug uptake in small abdominal tumors compared to normothermic perfusion or traditional bolus injection, suggesting that mild hyperthermia may not provide additional benefits in this context.

Both hyperthermic and normothermic perfusion achieved similar plasma drug levels, indicating that the method of drug delivery may be more important than the temperature used during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of cisplatin after intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC). Zeamari, S., Floot, B., van der Vange, N., et al.[2013]

In a study of 78 patients with stage III gallbladder cancer, hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) combined with radical surgery and capecitabine significantly improved median survival time to 19.2 months compared to 15.3 months for the control group receiving only surgery and capecitabine.

The HIPEC treatment did not increase surgery-related complications, indicating it is a safe option for enhancing survival in patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy Combined with Radical Surgery and Capecitabine on Stage III Gallbladder Cancer. Liu, S., Zhong, Z., Yi, W., et al.[2021]

In a study involving 184 patients with advanced primary ovarian cancer, the use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery resulted in lower consumption of non-opioid analgesics and reduced maximum pain intensity on the first postoperative day.

The findings suggest that HIPEC does not increase postoperative pain, indicating it can be safely integrated into treatment without exacerbating pain management challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of warm saline irrigation, hyperthermic intraperitoneal chemotherapy on postoperative pain in primary ovarian cancer from the KOV-HIPEC-01 randomized trial. Kim, JH., Park, KN., Park, EY., et al.[2023]

In a study evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer, combining hyperthermia with taxane chemotherapy did not enhance the cytotoxic effects on ovarian cancer cells, as the median lethal dose (LD50) remained consistent across different temperatures and exposure durations.

The findings suggest that, at the concentrations and durations tested, hyperthermia does not provide additional benefits in killing ovarian cancer cells when used with taxanes, indicating that further research may be needed to explore other combinations or methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cytotoxic effect of combined hyperthermia and taxane chemotherapy on ovarian cancer cells: results of an in vitro study. Muller, M., Chérel, M., Dupré, PF., et al.[2018]

In a study of 1,200 patients with peritoneal carcinomatosis treated with hyperthermic intraperitoneal chemotherapy (HIPEC), the procedure demonstrated a high objective remission rate of 95.6% for malignant ascites, indicating its effectiveness in this patient population.

The safety profile of HIPEC was favorable, with low rates of serious complications (e.g., 0.6% hemorrhage and 0.5% anastomotic leakage), and most adverse events were transient, suggesting that HIPEC can be a safe treatment option for patients with peritoneal carcinomatosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of High-Precision Hyperthermic Intraperitoneal Perfusion Chemotherapy in Peritoneal Carcinomatosis: A Real-World Study. Ba, M., Cui, S., Long, H., et al.[2022]

Hyperthermic intraperitoneal chemotherapy (HIPEC) for gastrointestinal cancers can lead to a range of significant side effects, including digestive fistulas, neutropenia, and renal impairment, as identified in a review of 79 articles.

Effective management strategies for these adverse events include forming a multidisciplinary team, considering alternative chemotherapy drugs, and utilizing careful preoperative assessments, which can help minimize the frequency and severity of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects of hyperthermic intraperitoneal chemotherapy in patients with gastrointestinal cancers. Hu, J., Wang, Z., Wang, X., et al.[2023]

Healthcare workers involved in hyperthermic intraperitoneal chemotherapy (HIPEC) are at risk of exposure to dangerous cytotoxic drugs, with evidence of environmental contamination in operating rooms and potential inhalation of harmful compounds.

There is a significant lack of standardized protective measures and biological monitoring for caregivers, highlighting the need for improved sampling methods and new biological indicators to effectively track and mitigate exposure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is hyperthermic intraperitoneal chemotherapy (HIPEC) safe for healthcare workers? Rodier, S., Saint-Lorant, G., Guilloit, JM., et al.[2018]

A systematic review and meta-analysis of six studies involving 674 patients indicated that hyperthermic intraperitoneal chemotherapy (HIPEC) can improve overall survival (OS) and disease-free survival (DFS) in patients with advanced epithelial ovarian cancer after neoadjuvant chemotherapy, particularly when using higher temperatures (≥42 °C) for shorter durations (≤60 min).

The addition of HIPEC did not lead to an increase in high-grade complications, suggesting it is a safe treatment option, especially when cisplatin is used as the chemotherapy agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Hyperthermic Intraperitoneal Chemotherapy Associated with Cytoreductive Surgery in the Treatment of Advanced Ovarian Cancer: Systematic Review and Meta-Analysis. Llueca, M., Ibañez, MV., Climent, MT., et al.[2023]

In patients with advanced epithelial ovarian cancer who underwent interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT), the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improved both progression-free survival (PFS) by 4.68 months and overall survival (OS) by 11.81 months compared to surgery alone, based on a review of 14 studies involving 1813 women.

However, in primary debulking surgery (PDS) and recurrent ovarian cancer (ROC), HIPEC did not show significant benefits in PFS or OS, and there was a slight increase in the risk of severe post-operative complications with the combined approach, indicating that while HIPEC can be beneficial in certain contexts, its role in other settings remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic Intraperitoneal Chemotherapy (HIPEC): New Approaches and Controversies on the Treatment of Advanced Epithelial Ovarian Cancer-Systematic Review and Meta-Analysis. Della Corte, L., Conte, C., Palumbo, M., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10856521/

Case Report and Rationale for a Prospective Clinical Trial Hyperthermic intraperitoneal chemotherapy (HIPEC) has efficacy in gallbladder cancer patients with macroscopic peritoneal disease undergoing ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8519707/

Effect of Hyperthermic Intraperitoneal Perfusion ... 76.71%, and the 2-year survival rates were 26.29% vs. 17.53%, respectively (P < 0.05). Conclusion. HIPEC combined with radical surgery and ...

3. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1361017/full

Cytoreductive surgery combined with hyperthermic ... In this article, we report five cases of advanced and recurrent GBC treated with a novel approach consisting of cytoreductive surgery (CRS) ...

4. wjgnet.com wjgnet.com/1948-9366/full/v15/i11/2413.htm

Effects of cytoreductive surgery combined with ... Compared with intravenous chemotherapy, HIPEC treatment alleviates adverse reactions and improves patient tolerance, delivering a more effective ...

5. uofmhealth.org uofmhealth.org/our-care/specialties-services/hyperthermic-intraperitoneal-chemotherapy-hipec

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a process in which heated chemotherapy is pumped directly into the abdomen after surgery.

6. hpbonline.org hpbonline.org/article/S1365-182X(18)31142-0/fulltext

Hyperthermic intraperitoneal chemotherapy in gall bladder ... Conclusion: This is the first study reporting use of HIPEC in gall bladder cancer. We found that HIPEC after extended cholecystectomy is well tolerated and safe ...