PIPAC for Peritoneal Cancer

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Anthracyclines, Platinum compounds

Disqualifiers: Metastatic disease, Bowel obstruction, others

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

Compensation: Varies

Number of Visits: 15

Duration: 12-18 weeks

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new chemotherapy delivery method called PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy) for cancers that have spread to the abdomen, such as ovarian, uterine, stomach, or colorectal cancer. PIPAC uses a fine mist of chemotherapy to target cancer cells directly in the abdomen, potentially reducing side effects compared to traditional methods. Treatment plans vary based on the type of cancer, each using specific chemotherapy drugs. Suitable patients have one of these abdominal cancers and have not responded to other chemotherapy treatments. As a Phase 1 trial, this research aims to understand how PIPAC works in people, offering patients the opportunity to be among the first to receive this innovative treatment.

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, it mentions that patients should not be receiving other investigational or concurrent anti-cancer agents, and there are specific time frames for stopping chemotherapy or surgery before enrollment. It's best to discuss your current medications with the trial team.

What prior data suggests that this PIPAC technique is safe for treating peritoneal cancer?

Research has shown that combining PIPAC treatments with various chemotherapy drugs is promising in terms of safety. For instance, when PIPAC is used with oxaliplatin, leucovorin, and fluorouracil, studies have found this method safe and practical for patients with certain cancers that have spread to the abdomen. Patients generally tolerate these treatments well, with an acceptable safety profile.

Similarly, using PIPAC with doxorubicin and cisplatin has shown low toxicity, making it a promising option for patients with specific abdominal cancers.

Lastly, PIPAC combined with mitomycin and FOLFIRI (a chemotherapy regimen) also demonstrates encouraging safety results. The treatment is practical and manageable, with patients handling it well.

Overall, these combinations of PIPAC and chemotherapy drugs have shown safety in studies, suggesting they are well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for peritoneal cancer because they use a novel delivery method called Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). Unlike traditional chemotherapy, which is typically administered intravenously, PIPAC delivers chemotherapy drugs directly to the peritoneal cavity in an aerosol form. This targeted approach allows for higher local concentrations of the drugs with potentially fewer systemic side effects. Additionally, the trial includes different combinations of drugs like oxaliplatin, doxorubicin, and mitomycin, which are tailored for various types of peritoneal cancer, offering personalized treatment options that could improve effectiveness and patient outcomes.

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

Research has shown that PIPAC, one of the treatments in this trial using oxaliplatin, leucovorin, and fluorouracil, shows early signs of effectiveness for peritoneal cancer. In one study, patients experienced a 53% reduction in their cancer index, which measures the size and spread of tumors. These treatments have been safe and well-tolerated, with promising early results.

Another treatment arm in this trial involves PIPAC with doxorubicin and cisplatin. Studies have shown it is well tolerated in patients with ovarian cancer, with patients reporting a better quality of life and longer survival times.

PIPAC with mitomycin and FOLFIRI, also being tested in this trial, has shown positive results. A study found that patients lived an average of 10.5 months from the start of treatment, suggesting a potential benefit for those with peritoneal cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Thanh H. Dellinger

Principal Investigator

City of Hope Medical Center

Mustafa Raoof, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with ovarian, uterine, gastric, appendiceal or colorectal cancer that has spread to the abdominal lining. They must have had at least one chemotherapy regimen and be in good enough health for a laparoscopy. Women who can bear children and men with partners of this group must use effective contraception.

Inclusion Criteria

Your platelet count is at least 100,000 per cubic millimeter.

Your hemoglobin level is at least 9 grams per deciliter.

My peritoneal disease is visible on scans or through a diagnostic procedure.

Exclusion Criteria

Arm 2 (colorectal/appendiceal): Involvement in the planning and conduct of the study

Arm 3 (colorectal/appendiceal): Patients may not be receiving any other investigational anti-cancer agents

I am on exclusive IV nutrition for my colorectal/appendiceal condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo PIPAC treatment with chemotherapy drugs such as doxorubicin, cisplatin, oxaliplatin, leucovorin, fluorouracil, and mitomycin. Treatment repeats every 4-6 weeks for up to 3 cycles.

12-18 weeks

3 cycles with multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including CT scans and quality of life evaluations.

18 weeks

Regular follow-up visits every 12 weeks for up to 3 years

Long-term follow-up

Participants are followed up every 12 weeks for up to 3 years to monitor progression-free survival and other long-term outcomes.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Biopsy
• Cisplatin
• Doxorubicin
• Fluorouracil
• Irinotecan
• Leucovorin
• Mitomycin
• Oxaliplatin
• PIPAC

Trial Overview

The trial tests PIPAC, a minimally invasive procedure delivering aerosolized chemotherapy directly into the abdomen during laparoscopy. It aims to see if this method reduces side effects compared to traditional methods by using lower doses of drugs like cisplatin and doxorubicin.

How Is the Trial Designed?

Group I: Arm IV (PIPAC, Cisplatin and nab-paclitaxel) Experimental Treatment 5 Interventions

Patients with recurrent ovarian cancer ( platinum-resistent or platinum metastases) patients with unresectable peritoneal metastases who are not candidates for cytoreductive surgery, at least 6 months after completion of first-line standard of care chemotherapy, and no bowel obstruction. Treatment for each 28-day cycle will consist of PIPAC with cisplatin (15 mg/m2) and nab-paclitaxel (90 mg/m2) on D1 every 28 days. A dose de-escalation plan is provided if the starting dose is not well-tolerated.

Group II: Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting Experimental Treatment 8 Interventions

Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting Experimental Treatment 7 Interventions

Patients with colorectal or appendiceal cancer undergo PIPAC with oxaliplatin IP. For cycles 2 and 3, patients receive leucovorin IV over 10 minutes and fluorouracil IV over 15 minutes 1-24 hours before undergoing PIPAC. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

Group IV: Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting Experimental Treatment 6 Interventions

Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with doxorubicin IP, followed by cisplatin IP. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Complete cytoreductive surgery (CCS) combined with Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) offers a significant survival advantage for patients with peritoneal carcinomatosis (PC), achieving a 5-year overall survival rate of 30-60%, compared to 0-5% with systemic chemotherapy alone.

The ongoing phase I/II trial aims to assess the safety and maximum tolerated dose of high-dose oxaliplatin administered via Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC), with the hypothesis that higher doses could enhance tumor response and improve patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of oxaliplatin dose escalation via a laparoscopic approach using pressurized aerosol intraperitoneal chemotherapy (PIPOX trial) for nonresectable peritoneal metastases of digestive cancers (stomach, small bowel and colorectal): Rationale and design. Dumont, F., Senellart, H., Pein, F., et al.[2022]

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]

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]

Cisplatin (CDDP) has been a key treatment for various cancers since 1972, but its use is limited by significant toxicities, particularly renal impairment.

Carboplatin (CBDCA), a second-generation analogue of cisplatin, has shown reduced renal toxicity and is effective against advanced cancers, although it can cause myelosuppression, particularly affecting platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second-generation cisplatin analogs]. Ariyoshi, Y., Ota, K.[2013]

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]

Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-OX) appears to be a safe treatment option for patients with colorectal peritoneal metastases (CPM), with no reported deaths related to the procedure and no occupational exposure to platinum detected during treatment.

The current evidence on the efficacy of PIPAC-OX for CPM is limited and difficult to interpret due to a lack of stratification in studies; however, it shows potential for safety and effectiveness, suggesting a need for more detailed reporting in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-OX) in patients with colorectal peritoneal metastases-a systematic review. Lurvink, RJ., Rovers, KP., Nienhuijs, SW., et al.[2021]

In a phase II trial involving 53 women with recurrent, platin-resistant ovarian cancer, Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) using cisplatin and doxorubicin showed a 62% objective tumor response rate and 76% tumor regression in patients who received all three treatments, indicating promising efficacy.

The ongoing phase III trial will compare PIPAC C/D to standard systemic chemotherapy in 244 patients, focusing on progression-free survival and quality of life, with the expectation that PIPAC C/D will better control peritoneal disease and maintain patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PIPAC-OV3: A multicenter, open-label, randomized, two-arm phase III trial of the effect on progression-free survival of cisplatin and doxorubicin as Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) vs. chemotherapy alone in patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer. Bakrin, N., Tempfer, C., Scambia, G., et al.[2022]

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]

In a Phase I study involving 23 patients with peritoneal metastases, PIPAC using nanoparticle albumin bound paclitaxel (NAB-PTX) demonstrated a favorable pharmacokinetic profile and resulted in a 35% response rate, indicating promising anticancer activity.

The maximum tolerated dose of NAB-PTX was determined to be 140 mg/m2, with stable quality of life scores and an overall survival rate of 57% after one year, suggesting that this treatment could be a viable option for patients with unresectable peritoneal metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of intraperitoneal aerosolized nanoparticle albumin based paclitaxel (NAB-PTX) for unresectable peritoneal metastases. Ceelen, W., Sandra, L., de Sande, LV., et al.[2022]

In a study involving 101 patients with unresectable peritoneal cancer, PIPAC using oxaliplatin was found to be a safe treatment option, with only 15.9% experiencing severe toxicity (grade 4 or higher).

The treatment provided good symptom control, with 50 patients reporting symptom improvement, suggesting that PIPAC-Ox may enhance the quality of life for those with advanced peritoneal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study. Sgarbura, O., Hübner, M., Alyami, M., et al.[2020]

In a phase I dose escalation study involving 13 patients, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) demonstrated safety with no dose-limiting toxicities or major side effects, allowing for higher doses of chemotherapy drugs than previously used.

The study established that oxaliplatin can be safely administered at 135 mg/m2, while cisplatin and doxorubicin can be used at 30 mg/m2 and 6 mg/m2, respectively, indicating that PIPAC can effectively deliver higher doses of chemotherapy with good tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis. Robella, M., De Simone, M., Berchialla, P., et al.[2021]

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