PIPAC and Surgery for Stomach Cancer

(EPICURE Trial)

Not yet recruiting at 4 trial locations

Overseen By Martin Graversen, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Odense University Hospital

Must be taking: Neoadjuvant chemotherapy

Must not be taking: Cisplatin, Doxorubicin

Disqualifiers: Renal impairment, Myocardial insufficiency, 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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of administering chemotherapy for individuals with high-risk stomach cancer. It examines whether pressurized chemotherapy directly in the abdomen after surgery helps patients remain cancer-free in the abdominal area for a year. Participants will receive either this new treatment, which includes chemotherapy drugs like Cisplatin and Doxorubicin, or standard surgery alone. Suitable candidates have stomach cancer that invades deeper stomach layers or exhibits specific aggressive features and are undergoing surgery to remove part of the stomach using a minimally invasive method. As a Phase 2 trial, this research focuses on evaluating 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 team or your doctor.

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

Research has shown that pressurized intraperitoneal chemotherapy (PIPAC) with cisplatin and doxorubicin is generally safe for patients. Earlier studies reported no deaths or extremely severe side effects from this treatment. Only about 16% of patients experienced serious but manageable side effects.

This method of administering chemotherapy distributes the drugs more evenly in the body, potentially leading to better results with fewer side effects than traditional methods. Although researchers continue to study this treatment, findings suggest that patients tolerate it well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the PIPAC treatment for stomach cancer because it uses a novel delivery method that directly targets the abdominal cavity, allowing for higher concentrations of chemotherapy drugs right at the tumor site. Unlike standard treatments, which often involve systemic chemotherapy circulating throughout the body, PIPAC delivers cisplatin and doxorubicin in a pressurized, aerosolized form. This approach not only enhances drug absorption by the cancer cells but also minimizes systemic side effects, potentially offering a more effective and tolerable option for patients.

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

In this trial, one group of participants will receive pressurized intraperitoneal chemotherapy (PIPAC) with cisplatin and doxorubicin. Research has shown that PIPAC may be promising for treating stomach cancer, particularly when it has spread within the abdominal area. Studies have found that PIPAC can lead to better long-term results when combined with systemic treatments. Early data suggest that this method can safely shrink tumors in some patients. Delivering cisplatin and doxorubicin directly to the cancer site effectively targets cancer cells. This approach might offer a focused way to manage advanced stomach cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Michael Bau Mortensen, DMSci, PhD

Principal Investigator

University of Southern Denmark (sdu.dk)

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with high-risk gastric cancer who can undergo minimally invasive surgery and are in good physical condition (ECOG 0-1). They must not have had allergic reactions to the chemotherapy drugs being tested, nor should they have severe heart, liver, or kidney problems. Women of childbearing age need a negative pregnancy test and must use birth control.

Inclusion Criteria

Able and willing to provide written informed consent and to comply with the clinical study protocol

I am fully active or can carry out light work.

My cancer can be of any grade.

Exclusion Criteria

I am allergic to cisplatin, doxorubicin, or similar drugs.

My kidney function is reduced, with a GFR less than 40 ml/min.

I have severe heart problems that limit my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial PIPAC Treatment

Participants undergo minimally invasive D2 gastrectomy followed by pressurized intraperitoneal chemotherapy (PIPAC) with cisplatin and doxorubicin

Immediate post-surgery

1 visit (in-person)

Second PIPAC Treatment

The PIPAC procedure is repeated 6-8 weeks postoperatively before the start of adjuvant systemic chemotherapy

6-8 weeks after initial treatment

1 visit (in-person)

Follow-up

Participants are monitored for peritoneal disease-free survival and other outcomes with at least 12 months follow-up

12 months

Regular follow-up visits (in-person and/or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Doxorubicin

Trial Overview The study tests if PIPAC therapy after minimally invasive stomach cancer surgery improves disease-free survival at one year compared to standard treatment. Patients will receive PIPAC immediately after surgery and again after 6-8 weeks.

How Is the Trial Designed?

Group I: Pressurized intraperitoneal chemotherapy (PIPAC) Experimental Treatment 2 Interventions

In the intervention arm, conventional pressurized intraperitoneal chemotherapy (PIPAC) with cisplatin (10.5 mg/m2 body surface in 150ml saline) and doxorubicin (2.1 mg/m2 body surface in 50ml saline) is performed through Medical Device Regulation (MDR) class IIb the CE-certified nebuliser by certified PIPAC surgeons directly after the completion of the minimally invasive gastric resection and reconstruction using the remaining relevant ports. Chemotherapy is administered through a CE-certified nebulizer according to the manufacturer's manual and followed by 30 minutes of simple diffusion. The carbondioxide is evacuated through a closed system, and the abdominal wall is closed according to local surgical standards. The same procedure is repeated, incorporating the same compounds and dose regimens six to eight weeks postoperatively and before the start of the adjuvant part of the perioperative systemic chemotherapy.

Group II: Standard Active Control 1 Intervention

In the control arm, patients will undergo minimally invasive D2 gastrectomy

Who Is Running the Clinical Trial?

Odense University Hospital

Lead Sponsor

Trials

808

Recruited

1,272,000+

Karolinska University Hospital

Collaborator

Trials

509

Recruited

1,319,000+

Published Research Related to This Trial

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]

The study evaluated the safety of a triple combination therapy of Paclitaxel (PTX), Cisplatin (CDDP), and 5-fluorouracil (5-FU) in 12 patients with unresectable or recurrent gastric cancer, finding it to be a safe treatment option despite some cases of hematological and non-hematological toxicities.

While there were instances of grade 3 or higher toxicities, including leukopenia and neutropenia, no infections occurred, and the maximum tolerated dose of 5-FU was determined to be 400 mg, indicating that the combination therapy can be administered with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel, cisplatin and 5-fluorouracil combination chemotherapy for unresectable / recurrent gastric cancer. Kato, J., Nagahara, A., Iijima, K., et al.[2015]

In a study of 762 patients undergoing cisplatin chemotherapy, 21.7% experienced nephrotoxicity, with significant risk factors including high-dose cisplatin, cardiac disease, and hypertension.

Magnesium supplementation and diuretic use were found to reduce the risk of cisplatin nephrotoxicity, suggesting they could be effective preventive measures for at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors for Cisplatin-Induced Nephrotoxicity: A Multicenter Retrospective Study. Miyoshi, T., Uoi, M., Omura, F., et al.[2021]

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a safe and well-tolerated treatment for peritoneal metastasis, with no procedure-related mortality and low complication rates (2.8% intraoperative and 4.9% postoperative) observed in a study of 71 patients.

In 67% of patients who underwent multiple PIPAC procedures, there was either tumor regression or stable disease, indicating that PIPAC can effectively induce histological improvements in heavily pretreated patients, with a median survival of 11.8 months following the first treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, Safety, and Efficacy of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastasis: A Registry Study. Kurtz, F., Struller, F., Horvath, P., et al.[2023]

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising new method for delivering chemotherapy directly into the peritoneal cavity, showing improved local bioavailability compared to traditional methods.

In a study comparing pegylated liposomal doxorubicin to conventional doxorubicin, the pegylated formulation resulted in lower tissue concentrations, suggesting that the aerosol delivery method may affect the stability and effectiveness of certain drug formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the Use of Pegylated Liposomal Doxorubicin (Caelyx®) as Pressurized Intraperitoneal Aerosol Chemotherapy. Robella, M., Vaira, M., Argenziano, M., et al.[2020]

In a study involving 20 gastric cancer patients with peritoneal metastasis, pressurized intraperitoneal aerosol chemotherapy (PIPAC) using low doses of cisplatin and doxorubicin showed a 36% objective tumor response rate, indicating its potential effectiveness in this challenging condition.

The treatment was well-tolerated with only minor postoperative complications, and the median survival after the first PIPAC procedure was 4.7 months, suggesting that PIPAC could be a promising option for improving outcomes in patients with peritoneal metastasis from gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) of peritoneal metastasis from gastric cancer: a descriptive cohort study. Ellebæk, SB., Graversen, M., Detlefsen, S., et al.[2020]

In a study involving 47 patients with unresectable peritoneal metastases, pressurized intraperitoneal chemotherapy (PIPAC) using taxanes was found to be feasible and safe, with 51% of patients experiencing mild complications and 12.7% facing more severe complications.

PIPAC treatment led to a clinical response in 34% of patients, and 19.1% of patients became operable after treatment, indicating potential for improved outcomes in managing peritoneal metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of Taxane-PIPAC in Patients with Peritoneal Malignancies-a Retrospective Bi-institutional Study. Mehta, S., Kammar, P., Patel, A., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37875869/

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) ... Some preliminary data suggest PIPAC can achieve improved long-term outcomes in patients with GC PM, especially when used in combination with systemic ...

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11549-z

Pressurized intraperitoneal aerosol chemotherapy (PIPAC ... Some preliminary data suggest PIPAC can achieve improved long-term outcomes in patients with GC PM, especially when used in combination with ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.4_suppl.99

Pressurized intraperitoneal aerosol chemotherapy with low ... Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis ( ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04329494

Study Details | NCT04329494 | PIPAC for the Treatment of ... This phase I trial studies the side effects of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in treating patients with ovarian, uterine, appendiceal ...

5. jogs.org jogs.org/article/S1091-255X(23)06384-9/fulltext

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC ... PIPAC with low-dose cisplatin and doxorubicin was safe and induced objective tumor regression in selected patients with PM from recurrent, platinum-resistant GC ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0748798324015671

Review Article Outcomes of intraperitoneal chemotherapy ... Macroscopic peritoneal metastases are detected in 10–21 % of gastric cancer patients at first presentation [4] and are associated with a median survival of 3–6 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26511950/

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC ... PIPAC with low-dose cisplatin and doxorubicin was safe and induced objective tumor regression in selected patients with PM from recurrent, platinum-resistant ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01854255

Intraperitoneal Aerosol Chemotherapy in Gastric Cancer Objectives: To evaluate the safety and efficacy in terms of the clinical benefit rate (CBR) of PIPAC in peritoneal carcinomatosis (PC) from gastric cancer (GC) ...