Aerosolized Chemotherapy for Biliary Tract Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers/inhibitors, Antibiotics

Disqualifiers: Liver metastases, Brain metastases, others

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

Compensation: Varies

Number of Visits: 9

Duration: 24 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to deliver chemotherapy for biliary tract cancer that has spread to the abdomen. It uses a special technique to turn chemotherapy into a mist, targeting cancer cells more effectively while potentially reducing side effects. Participants will receive a combination of three chemotherapy drugs: nab-paclitaxel, gemcitabine, and cisplatin. This trial may suit those diagnosed with biliary tract cancer that has spread to the abdomen and who have not yet received systemic treatment for advanced stages of the disease. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot take strong CYP3A4 inducers/inhibitors or therapeutic antibiotics within 14 days before starting the trial. It's best to discuss your current medications with the trial team.

What prior data suggests that this method is safe for treating biliary tract cancer?

A previous study showed promising results by adding nab-paclitaxel to the chemotherapy drugs gemcitabine and cisplatin. Patients tolerated the treatment well, and side effects were manageable. The treatment uses a device to spray chemotherapy directly into the abdomen, helping the drug reach more tissue and potentially causing fewer side effects.

Gemcitabine and cisplatin are well-known chemotherapy drugs safely used in many patients with various cancers. Nab-paclitaxel has also been tested in different contexts and is already approved for some other cancers, indicating an acceptable safety profile.

Since this trial is in an early stage, it focuses on safety. Early trials usually start with low doses, ensuring the treatment is administered carefully to avoid adverse reactions. So far, using pressurized intraperitoneal aerosolized chemotherapy (PIPAC) with nab-paclitaxel appears well-tolerated. However, participants will be closely monitored for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about this new treatment for biliary tract cancer because it uses a novel delivery method called Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC). Unlike traditional chemotherapy, which is usually administered intravenously, PIPAC delivers drugs directly into the abdominal cavity in a pressurized aerosol form. This approach may enhance drug penetration into tumors and reduce systemic side effects. Additionally, the combination of gemcitabine, cisplatin, and nab-paclitaxel is administered in a precise schedule that maximizes their synergistic effects, potentially offering improved outcomes for patients who have limited options with current treatments.

What evidence suggests that this aerosolized chemotherapy is effective for biliary tract cancer?

This trial will evaluate the combination of gemcitabine, cisplatin, and nab-paclitaxel delivered via Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) for treating biliary tract cancer. Research has shown that this combination, when studied, did not improve progression-free survival or overall survival compared to standard chemotherapy. The PIPAC method sprays drugs as a mist directly into the abdomen, aiming to enhance drug delivery to the cancer and reduce side effects. Although this method appears promising, it has not yet proven more effective in this context. Current evidence suggests that further research is needed to confirm any potential benefits. ^{6 7 8 9 10}

Who Is on the Research Team?

Daneng Li, MD

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 biliary tract cancer that has spread to the lining of their abdomen. They must have certain blood counts, liver and kidney function, no HIV or controlled hepatitis, and not be pregnant. They can't join if they've had other cancers (except some skin cancers), brain metastases, severe uncontrolled illnesses, significant neuropathy, or recent strong drug interactions.

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative

Serum albumin >= 2.8 g/dL within 28 days prior to day 1 of protocol therapy

ALT =< 5 x ULN within 28 days prior to day 1 of protocol therapy

Exclusion Criteria

Life expectancy < 3 months

I have had treatments for a blocked intestine.

I have not taken any strong antibiotics in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gemcitabine and cisplatin intravenously on days 1 and 8, and nab-paclitaxel via PIPAC on day 3 of cycles 1, 3, and 5. Treatment repeats every 21 days for up to 8 cycles.

24 weeks

8 cycles with multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 4 weeks and every 3 months thereafter.

Up to 1 year

1 visit at 4 weeks, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Gemcitabine
• Nab-paclitaxel
• Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC)

Trial Overview

The trial tests a new way to deliver chemotherapy called PIPAC with nab-paclitaxel combined with gemcitabine and cisplatin in patients whose biliary tract cancer has spread within the abdomen. It aims to see if this method reduces side effects while effectively treating the cancer.

How Is the Trial Designed?

Group I: Treatment (gemcitabine, cisplatin, nab-paclitaxel PIPAC) Experimental Treatment 5 Interventions

Patients receive gemcitabine IV over 30 minutes and cisplatin IV over 60 minutes on days 1 and 8. Patients also receive nab-paclitaxel via PIPAC over 5-10 minutes on day 3 of cycles 1, 3, and 5. Treatment repeats every 21 days for up to 8 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

In a retrospective study of 29 patients with advanced pancreatic carcinoma and elevated bilirubin levels, treatment with nanoparticle albumin-bound paclitaxel and gemcitabine (nab-P/G) was found to be safe, showing no unexpected toxicities.

The median overall survival for patients treated with nab-P/G was 11.7 months, with no significant differences in survival based on bilirubin levels, indicating that nab-P/G is a feasible treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis. Pelzer, U., Wislocka, L., Jühling, A., et al.[2022]

In a phase II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) using low-dose doxorubicin and cisplatin showed objective tumor regression in 4 out of 5 patients with peritoneal metastasis of biliary tract cancer, indicating its potential efficacy against chemotherapy-resistant cases.

Despite the promising results, nearly two-thirds of patients experienced rapid clinical deterioration, limiting their ability to receive multiple PIPAC treatments, which highlights a significant challenge in the treatment's application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Clinical Data of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) as Salvage Therapy for Peritoneal Metastatic Biliary Tract Cancer. Falkenstein, TA., Götze, TO., Ouaissi, M., et al.[2022]

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was found to be feasible and safe for treating peritoneal metastases from pancreatic adenocarcinoma (PDAC) and cholangiocarcinoma (CC), with only one intraoperative complication and 18 mild postoperative adverse events reported among 20 patients.

The study showed a 50% pathological regression rate in patients treated with PIPAC, indicating promising antitumoral activity, with median survival times of 9.7 months for PDAC and 10.9 months for CC, suggesting potential for further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin or oxaliplatin for peritoneal metastasis from pancreatic adenocarcinoma and cholangiocarcinoma. Di Giorgio, A., Sgarbura, O., Rotolo, S., et al.[2022]

A phase I study is being conducted to evaluate the safety and determine the maximum tolerated dose of albumin-bound paclitaxel (ABP) delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal metastases from various cancers.

The study will involve three treatments with ABP, escalating the dose from 35 to 140 mg/m², and will assess not only toxicity but also factors like surgical morbidity and quality of life, aiming to set the stage for future randomized phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. Van De Sande, L., Graversen, M., Hubner, M., 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]

Nab-paclitaxel, a new formulation of paclitaxel, has shown a good safety and efficacy profile for treating metastatic breast cancer (MBC), although there is limited data on its impact on overall survival.

In combination with gemcitabine, nab-paclitaxel significantly improves survival in advanced pancreatic cancer (PC) and demonstrates better results in non-small-cell lung cancer (NSCLC) patients with squamous histology, highlighting its potential as a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. Cecco, S., Aliberti, M., Baldo, P., et al.[2015]

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