Aerosolized Chemotherapy for Biliary Tract Cancer

Overseen by Daneng Li, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers/inhibitors, Antibiotics

Disqualifiers: Liver metastases, Brain metastases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial studies a new way to deliver chemotherapy directly into the abdomen as a fine mist for patients with biliary tract cancer that has spread. The goal is to see if this method, combined with standard chemotherapy, is safe and more tolerable. The fine mist helps the drugs reach more tissue and may reduce side effects. Gemcitabine, often combined with cisplatin, is a standard chemotherapy for advanced biliary tract cancer.

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 data supports the effectiveness of this treatment for biliary tract cancer?

Research suggests that using pressurized intraperitoneal aerosol chemotherapy (PIPAC) with nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) may be effective for treating peritoneal metastases, as it has shown promise in other cancers like pancreatic and ovarian cancer. Additionally, nab-Paclitaxel combined with gemcitabine has been effective in treating advanced pancreatic cancer, which shares some characteristics with biliary tract cancer. ^{1 2 3 4 5}

Is aerosolized chemotherapy with nab-paclitaxel safe for humans?

Research shows that nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has been studied for safety in humans, including in treatments for various cancers like breast, lung, and pancreatic cancer. It is generally considered safe and is approved for use in several countries, with studies indicating it avoids some toxicities associated with other formulations. ^{1 2 4 6 7}

How is the treatment for biliary tract cancer using PIPAC with Cisplatin, Gemcitabine, and Nab-paclitaxel different from other treatments?

This treatment is unique because it uses pressurized intraperitoneal aerosol chemotherapy (PIPAC), which delivers chemotherapy directly into the abdominal cavity as a spray, potentially increasing drug exposure to cancer cells in the peritoneum (the lining of the abdominal cavity) compared to traditional methods. ^{1 2 3 4 5}

Research Team

Daneng Li, MD

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 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.

Trial Timeline

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

Treatment Details

Interventions

• Cisplatin (Alkylating agents)
• Gemcitabine (Anti-metabolites)
• Nab-paclitaxel (Anti-tumor antibiotic)
• Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) (Procedure)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Robert Stone

City of Hope Medical Center

Chief Executive Officer since 2014

Juris Doctorate from the University of Chicago, Bachelor's degree in Political Science from the University of Redlands

Sumanta (Monty) Pal

City of Hope Medical Center

Chief Medical Officer since 2023

MD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human 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. Greece pubmed.ncbi.nlm.nih.gov

First Clinical Data of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) as Salvage Therapy for Peritoneal Metastatic Biliary Tract Cancer. [2022]

4. England 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. [2022]

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

Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin or oxaliplatin for peritoneal metastasis from pancreatic adenocarcinoma and cholangiocarcinoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. [2015]

7. England pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. [2023]