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 phase II trial studies the effects of hyperthermic intraperitoneal chemotherapy (HIPEC) in treating patients with pancreatic cancer that has spread to the internal abdominal area (peritoneal metastasis). Chemotherapy drugs, such as nab-paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. HIPEC involves "heated" chemotherapy that is placed directly in the abdomen through laparoscopic instruments, instead of through an intravenous injection. This study may help doctors determine how safe and effective HIPEC work in treating patient with pancreatic cancer.

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 heated chemotherapy generally safe for humans?

Heated chemotherapy (HIPEC) using drugs like cisplatin, paclitaxel, mitomycin C, and oxaliplatin has been studied for safety in various cancers, including ovarian and colorectal cancer. These studies suggest that while there are some risks, the treatment is generally considered safe, with oxaliplatin showing less perioperative morbidity (complications around the time of surgery) compared to mitomycin C. ^{1 2 3 4 5}

How is the heated chemotherapy treatment for metastatic pancreatic cancer different from other treatments?

This treatment is unique because it combines heated chemotherapy (HIPEC) with multiple drugs, including cisplatin, mitomycin, and paclitaxel, delivered directly into the abdominal cavity to target cancer cells more effectively. The use of heat enhances the effectiveness of the chemotherapy, and this approach is particularly promising for cancers that have spread to the lining of the abdomen, offering a novel way to treat metastatic pancreatic cancer. ^{5 6 7 8 9}

What data supports the effectiveness of the treatment Heated Chemotherapy for Metastatic Pancreatic Cancer?

Research on similar treatments, like hyperthermic intraperitoneal chemotherapy (HIPEC) with drugs such as cisplatin and mitomycin C, shows promise in treating other cancers like ovarian and gastric cancer. These studies suggest that combining heat with chemotherapy can enhance the treatment's effectiveness, although specific data for pancreatic cancer is not provided. ^{6 7 8 10 11}

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

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. France pubmed.ncbi.nlm.nih.gov

[Intraperitoneal chemo-hyperthermia in the treatment of peritoneal carcinomatosis of ovarian origin. Initial cases, physiopathologic data]. [2013]

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

Impact of hyperthermia on pharmacokinetics of intraperitoneal mitomycin C in rats investigated by microdialysis. [2014]

3. Netherlands pubmed.ncbi.nlm.nih.gov

In vitro cytotoxicity of paclitaxel/beta-cyclodextrin complexes for HIPEC. [2015]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Intraperitoneal hyperthermic chemotherapy in ovarian cancer. [2018]

6. United States 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. [2022]

7. England 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. [2018]

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

In vivo toxicity and bioavailability of Taxol and a paclitaxel/beta-cyclodextrin formulation in a rat model during HIPEC. [2015]

9. Romania 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. [2022]

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

A model based analysis of IPEC dosing of paclitaxel in rats. [2021]

11. Greece pubmed.ncbi.nlm.nih.gov

Regional chemotherapy (with mitomycin C) and intra-operative hyperthermia for digestive cancers with peritoneal carcinomatosis. [2013]