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

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in treating patients with ovarian, uterine, appendiceal, stomach (gastric), or colorectal cancer that has spread to the lining of the abdominal cavity (peritoneal carcinomatosis). Chemotherapy drugs, such as cisplatin, doxorubicin, oxaliplatin, leucovorin, fluorouracil, mitomycin, and irinotecan, 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. PIPAC is a minimally invasive procedure that involves the administration of intraperitoneal chemotherapy. The study device consists of a nebulizer (a device that turns liquids into a fine mist), which is connected to a high-pressure injector, and inserted into the abdomen (part of the body that contains the digestive organs) during a laparoscopic procedure (a surgery using small incisions to introduce air and to insert a camera and other instruments in the abdominal cavity for diagnosis and/or to perform routine surgical procedures). Pressurization of the liquid chemotherapy through the study device results in aerosolization (a fine mist or spray) of the chemotherapy intra-abdominally (into the abdomen). Giving chemotherapy through PIPAC may reduce the amount of chemotherapy needed to achieve acceptable drug concentration, and therefore potentially reduces side effects and toxicities.

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 data supports the effectiveness of PIPAC for peritoneal cancer?

Research shows that PIPAC, a method of delivering chemotherapy directly into the abdomen, has been effective in treating peritoneal cancer. In a study with 53 women, 62% had a reduction in tumor size, and 76% showed tumor regression after three PIPAC treatments. This suggests that PIPAC can be a promising option for patients with peritoneal cancer. ^{1 2 3 4 5}

Is PIPAC safe for treating peritoneal cancer?

PIPAC, which uses drugs like oxaliplatin, cisplatin, and doxorubicin, appears to be generally safe for treating peritoneal cancer. Studies show that it is well-tolerated, with common side effects being abdominal pain and nausea, and no deaths related to PIPAC have been reported. The treatment is also considered safe for medical staff handling it. ^{3 6 7 8 9}

What makes PIPAC for peritoneal cancer unique?

PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) is unique because it delivers chemotherapy drugs directly into the abdominal cavity as a pressurized aerosol, which improves the local availability of the drugs compared to traditional methods. This approach is particularly beneficial for treating peritoneal metastases, as it allows for higher concentrations of the drugs at the tumor site with potentially fewer systemic side effects. ^{1 2 3 10 11}

Research Team

Thanh H. Dellinger

Principal Investigator

City of Hope Medical Center

Mustafa Raoof, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Arm III (PIPAC, mitomycin, FOLFIRI) 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 II: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) 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 III: Arm I (PIPAC, doxorubicin, cisplatin) 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+

Findings from Research

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]

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 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]

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 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]

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 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]

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 (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]

References

1. India pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of Taxane-PIPAC in Patients with Peritoneal Malignancies-a Retrospective Bi-institutional Study. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Phase I study of intraperitoneal aerosolized nanoparticle albumin based paclitaxel (NAB-PTX) for unresectable peritoneal metastases. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Exploring the Use of Pegylated Liposomal Doxorubicin (Caelyx®) as Pressurized Intraperitoneal Aerosol Chemotherapy. [2020]

4. Germany 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. [2022]

5. Germany 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. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-OX) in patients with colorectal peritoneal metastases-a systematic review. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

[Second-generation cisplatin analogs]. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) of peritoneal metastasis from gastric cancer: a descriptive cohort study. [2020]

11. Egypt pubmed.ncbi.nlm.nih.gov

Feasibility, Safety, and Efficacy of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastasis: A Registry Study. [2023]