Heated Chemotherapy for Metastatic Pancreatic Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Disqualifiers: Solid organ metastases, Infections, Pregnancy, 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: 6

Duration: Varies based on number of HIPEC sessions

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a special chemotherapy treatment for individuals with pancreatic cancer that has spread to the abdominal area. The treatment, called Hyperthermic Intraperitoneal Chemotherapy, uses heated chemotherapy directly inside the abdomen, potentially targeting cancer cells more effectively than standard IV chemotherapy. The trial will assess the safety and effectiveness of this heated method. It suits those with pancreatic cancer showing visible signs in the abdominal area who have already responded to standard chemotherapy. As a Phase 2 trial, this research focuses on measuring 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 whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that hyperthermic intraperitoneal chemotherapy (HIPEC), when combined with nab-paclitaxel and cisplatin, is generally well-tolerated by patients. In previous studies, patients with pancreatic cancer that had spread to the abdomen did not experience severe side effects that required stopping treatment.

Further research found that a similar treatment had a promising one-year survival rate of 37%, indicating reasonable safety. Although this treatment is still under investigation, its use in other conditions has demonstrated relative safety. However, as individual reactions can vary, discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for metastatic pancreatic cancer, which typically involve systemic chemotherapy, this new approach utilizes Hyperthermic Intraperitoneal Chemotherapy (HIPEC). HIPEC delivers heated chemotherapy directly to the abdomen, allowing higher concentration of drugs like nab-paclitaxel and cisplatin to target cancer cells more effectively while minimizing systemic side effects. Researchers are excited about this method because the heat is believed to enhance the efficacy of the drugs, potentially improving outcomes for patients who have limited options with current therapies. Additionally, the ability to repeat the treatment up to five times offers a unique opportunity for continuous management of the disease.

What evidence suggests that this trial's treatments could be effective for metastatic pancreatic cancer?

Research has shown that hyperthermic intraperitoneal chemotherapy (HIPEC) could be promising for pancreatic cancer that has spread to the abdominal area. In this trial, participants will receive HIPEC combined with nab-paclitaxel and cisplatin. Studies have found that this combination can significantly reduce cancer spread in this region. Additionally, some participants may receive HIPEC with paclitaxel and cisplatin, which has been found to be as effective as using cisplatin alone, making it a viable option. Combining HIPEC with surgery can lead to better outcomes and appears safe for patients. Overall, these treatments have the potential to improve survival rates for patients with pancreatic cancer that has spread to the abdomen. ^{1 2 4 6 7}

Who Is on the Research Team?

Cornelius A. Thiels, DO, MBA

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with pancreatic cancer that has spread to the abdomen, who have responded well to prior chemotherapy. They must be in good physical condition (ECOG <=2), have a low tumor burden in the abdomen (PCI <=7), and adequate blood cell counts. Pregnant women or those unable to follow study procedures are excluded.

Inclusion Criteria

My test for KRAS mutation in abdominal fluid is positive.

My cancer has spread to the lining of my abdomen and tests confirm it.

My cancer spread is limited, confirmed by a surgical exam.

Exclusion Criteria

My cancer has spread to organs like the liver, brain, or lungs.

I can follow the study's requirements and attend all appointments.

I do not have infections like pneumonia that would stop me from following the treatment plan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

CT scan, MRI or PET

Treatment

Participants undergo HIPEC with nab-paclitaxel and cisplatin over 90 minutes, with the possibility of additional HIPEC sessions up to 5 times

Varies based on number of HIPEC sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 6 months

Up to 4 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Hyperthermic Intraperitoneal Chemotherapy
• Mitomycin
• Nab-paclitaxel
• Paclitaxel

Trial Overview The trial studies 'heated' chemo directly delivered into the abdomen of patients with pancreatic cancer after laparoscopic surgery. It tests how safe and effective this HIPEC method is using drugs like nab-paclitaxel and cisplatin compared to traditional intravenous methods.

How Is the Trial Designed?

Group I: Treatment (HIPEC) Experimental Treatment 6 Interventions

Patients undergo HIPEC with nab-paclitaxel and cisplatin over 90 minutes in the absence of disease progression or unacceptable toxicity. Patients may undergo additional HIPEC with paclitaxel and cisplatin up to 5 times. Patients undergo CT scan, MRI or PET during screening.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 13 women with epithelial ovarian cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) using cisplatin and paclitaxel resulted in high drug concentrations in the peritoneal tissue while maintaining low levels in the bloodstream, indicating a favorable pharmacokinetic profile.

The treatment was associated with some surgical complications, with four patients experiencing grade 3-4 complications, but overall, HIPEC was deemed feasible and showed potential for effective localized treatment after cytoreductive surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer. Ansaloni, L., Coccolini, F., Morosi, L., et al.[2018]

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]

Both the novel paclitaxel formulation (Pac/RAME-beta-CD) and Taxol had a similar maximum tolerated dose (MTD) of 0.24 mg/ml after hyperthermic intraperitoneal chemotherapy (HIPEC), indicating comparable toxicity profiles.

The novel formulation demonstrated a significantly higher bioavailability, with a 40-fold increase in plasma concentration area under the curve (AUC) compared to Taxol, suggesting it may be more effective in delivering the drug to target tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo toxicity and bioavailability of Taxol and a paclitaxel/beta-cyclodextrin formulation in a rat model during HIPEC. Bouquet, W., Ceelen, W., Adriaens, E., et al.[2015]

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]

This study presents the first results of using intraperitoneal hyperthermic chemotherapy with mitomycin C or cisplatin in four patients with advanced ovarian cancer, showing no post-operative complications.

The combination of hypothermia and chemotherapy not only helps to destroy tumor cells but also enhances the effectiveness of the chemotherapy, with two patients remaining alive 4 and 6 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intraperitoneal chemo-hyperthermia in the treatment of peritoneal carcinomatosis of ovarian origin. Initial cases, physiopathologic data]. Salle, B., Gilly, FN., Carry, PY., et al.[2013]

Intraperitoneal hyperthermic perfusion chemotherapy, used as a consolidation therapy after surgery and systemic chemotherapy in 29 patients with stage IIIB-IIIC ovarian cancer, was found to be well tolerated both locally and systemically.

Although the consolidation therapy group showed improved 5-year survival rates and lower recurrence rates compared to a control group, these differences were not statistically significant, suggesting that while promising, further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gori, J., Castaño, R., Toziano, M., et al.[2018]

A new formulation of paclitaxel using RAMEB as a vehicle showed similar cytotoxic effects to the traditional Taxol formulation, while being less toxic to cells, indicating a safer option for chemotherapy.

The study found that applying heat during treatment (41 degrees C for 1 hour) did not enhance the effectiveness of paclitaxel in killing cancer cells, suggesting that hyperthermia does not provide additional benefits in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro cytotoxicity of paclitaxel/beta-cyclodextrin complexes for HIPEC. Bouquet, W., Boterberg, T., Ceelen, W., et al.[2015]

Paclitaxel (PTX) shows a complex, non-linear dose-response relationship when administered via Hyperthermic Intraperitoneal Perioperative Chemotherapy (IPEC), indicating that absorption from the peritoneal cavity is not straightforward.

To enhance treatment effectiveness while reducing systemic toxicity in peritoneal carcinomatosis, the study suggests using lower doses of PTX with extended exposure times, supporting the idea that 'less is more' in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A model based analysis of IPEC dosing of paclitaxel in rats. Colin, P., De Smet, L., Vervaet, C., et al.[2021]

A review of 36 studies on mitomycin C and oxaliplatin used in hyperthermic intraperitoneal chemotherapy (HIPEC) after surgery for colorectal cancer showed that while both agents are safe, there is no clear consensus on which is superior due to study variability and lack of randomized trials.

Oxaliplatin-based HIPEC may result in lower perioperative morbidity compared to mitomycin C, but mitomycin C is considered more cost-effective, highlighting the need for further randomized trials to better understand their comparative effectiveness and impact on patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic Intraperitoneal Chemotherapy with Mitomycin C versus Oxaliplatin after Cytoreductive Surgery for the Treatment of Peritoneal Metastases of Colorectal Cancer Origin. Papageorgopoulou, C., Nikolakopoulos, K., Seretis, C.[2022]

Intraperitoneal chemo-hyperthermia using mitomycin C was safely administered to 28 patients with advanced digestive adenocarcinoma, showing no mortality and only 2 minor postoperative complications.

The treatment led to a significant improvement in patient outcomes, with a 54.2% one-year survival rate and successful clearance of malignant ascites in 9 out of 10 patients who had it before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional chemotherapy (with mitomycin C) and intra-operative hyperthermia for digestive cancers with peritoneal carcinomatosis. Gilly, FN., Carry, PY., Sayag, AC., et al.[2013]

In a multicenter phase-I study involving 30 patients with initially unresectable ovarian cancer, the recommended dose of cisplatin for hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant chemotherapy was determined to be 70 mg/m², as higher doses led to significant dose-limiting toxicities (DLTs).

The study found that at the highest dose of 80 mg/m², there were serious adverse events including renal failure and hemorrhage, highlighting the importance of careful dose selection to minimize toxicity while maximizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. Gouy, S., Ferron, G., Glehen, O., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04858009

Study Details | NCT04858009 | Hyperthermic ... This phase II trial studies the effects of hyperthermic intraperitoneal chemotherapy (HIPEC) in treating patients with pancreatic cancer that has spread to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8100705/

Hyperthermic intra-operative intraperitoneal chemotherapy ... HIPEC following R 0 resection is a feasible and safe adjuvant treatment for pancreatic cancer. The local-regional failures appear to be significantly decreased.

3. npcf.us npcf.us/clinical-trials/the-safety-and-effectiveness-of-hyperthermic-intraperitoneal-chemotherapy-combined-with-intravenous-chemotherapy-for-peritoneal-metastatic-pancreatic-cancer-a-phase-ii-clinical-trial/

The Safety And Effectiveness Of Hyperthermic ... The goal of this clinical trial is to evaluate the effectiveness and safety of hyperthermic intraperitoneal chemotherapy combined with intravenous ...

4. bmcsurg.biomedcentral.com bmcsurg.biomedcentral.com/articles/10.1186/s12893-024-02526-9

Efficacy and safety of intraperitoneal chemotherapy for ... A phase I study of intraperitoneal paclitaxel combined with gemcitabine plus nab-paclitaxel for pancreatic cancer with peritoneal metastasis.

5. trialx.com trialx.com/clinical-trials/listings/259762/hyperthermic-intraperitoneal-chemotherapy-for-the-treatment-of-pancreatic-cancer-and-peritoneal-metastasis/?&geo_lat=44.0496&geo_lng=-92.4896&radius=10&place=Rochester&user_country=United%20States

Hyperthermic Intraperitoneal Chemotherapy for the ... Patients undergo HIPEC with nab-paclitaxel and cisplatin over 90 minutes in the absence of disease progression or unacceptable toxicity.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11451220/

Efficacy and safety of intraperitoneal chemotherapy for ... A systematic review and meta-analysis on peritoneal malignancies of different origins showed a one-year survival rate of 37% in patients with ...

7. wjso.biomedcentral.com wjso.biomedcentral.com/articles/10.1186/s12957-024-03464-9

Efficacy and safety of cytoreductive surgery combined with ... The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer.