Chemotherapy + Y-90 for Bile Duct Cancer

Recruiting at 1 trial location

Overseen By Elahe Mollapour

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Inova Health Care Services

Must not be taking: Immunosuppressants

Disqualifiers: Pregnancy, Autoimmune diseases, Organ transplant, 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: Unknown

16 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to see if combining gemcitabine, cisplatin and Durvalumab chemotherapy treatments with a direct tumor therapy called Yittrium-90, will work better together to shrink the tumor and control cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that recent use of immunosuppressive medication is not allowed within 14 days before starting durvalumab, except for certain exceptions like low-dose steroids. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the chemotherapy and Y-90 treatment for bile duct cancer?

Research shows that combining gemcitabine with a platinum-based drug like cisplatin is a standard treatment for advanced biliary cancers, and nab-paclitaxel has shown promise in treating similar cancers. Additionally, nab-paclitaxel has been effective in treating other cancers, suggesting potential benefits for bile duct cancer. ^{1 2 3 4 5}

Is the combination of nab-paclitaxel and gemcitabine generally safe for humans?

Nab-paclitaxel, when combined with gemcitabine, has been shown to have a good safety profile with fewer side effects compared to other formulations in treating various cancers, including pancreatic and gastrointestinal cancers. ^{3 6 7 8 9}

What makes the Chemotherapy + Y-90 treatment for bile duct cancer unique?

This treatment combines chemotherapy drugs with Yttrium-90, a radioactive substance, to target bile duct cancer. The use of Yttrium-90 allows for direct radiation to the tumor, which is different from standard chemotherapy that typically involves only drugs like gemcitabine and cisplatin. ^{4 10 11 12 13}

Research Team

Arthur Winer, MD

Principal Investigator

Inova Schar Cancer Institute

Eligibility Criteria

This trial is for adults with intrahepatic cholangiocarcinoma (a type of bile duct cancer) that can't be removed by surgery. Participants must be at least 18, have a tumor at least 2 cm big, no cirrhosis or severe liver issues, and an ECOG score of 0-1 indicating they are fully active or restricted in physically strenuous activity but ambulatory. They should not have had previous chemotherapy for this cancer except certain adjuvant therapy.

Inclusion Criteria

My bile duct cancer is confirmed and either untreated or was last treated over 6 months ago.

My liver is healthy and I don't have cirrhosis.

My cancer cannot be surgically removed without risking liver function.

Exclusion Criteria

Over 75% of my liver is affected by cancer.

My tests show I can't safely receive certain liver cancer treatments due to risks found in my blood vessels.

Anticipated poor compliance

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction chemotherapy with Gemcitabine, Cisplatin, and Durvalumab

6 months

Radioembolization Treatment

Participants receive Gemcitabine, Cisplatin in combination with Yttrium-90 (Y-90) Radioembolization

6 months

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

48 months

Treatment Details

Interventions

• Cisplatin
• Gemcitabine
• Nab-paclitaxel
• Yittrium-90

Trial Overview The study tests if combining gemcitabine, cisplatin and nab-paclitaxel (chemotherapy drugs) with Yittrium-90 (Y-90), a direct tumor therapy, is more effective in shrinking tumors and controlling cancer than previous treatments. It involves initial 'induction' chemotherapy followed by Y-90 treatment then 'consolidation' therapy.

Participant Groups

Group I: gemcitabine, cisplatin and Durvalumab chemotherapy with Yittrium-90 Experimental Treatment 3 Interventions

single arm - Induction Gemcitabine, Cisplatin and Durvalumab Triplet Chemotherapy followed by Gemcitabine, Cisplatin in combination with yttrium-90 (Y-90) Radioembolization

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?

Inova Health Care Services

Lead Sponsor

Trials

80

Recruited

22,700+

Findings from Research

In a phase II pilot study involving 10 patients with advanced cholangiocarcinoma who were ineligible for cisplatin therapy, the combination of nab-paclitaxel and gemcitabine showed a promising overall response rate of 50% and a disease control rate of 90%.

The treatment demonstrated a median progression-free survival of 5.7 months and a median overall survival of 7.8 months, with no new safety concerns identified, indicating that this regimen is both effective and safe for patients who cannot tolerate standard cisplatin-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Nab-Paclitaxel and Gemcitabine as First-Line Therapy in Patients with Cholangiocarcinoma Ineligible for Cisplatin-Based Chemotherapy (NACHO). Virchow, I., Treckmann, JW., Prasnikar, N., et al.[2023]

Nab-paclitaxel, a solvent-free chemotherapy drug, showed promising clinical and serological responses in a 63-year-old patient with advanced cholangiocarcinoma after other treatments failed, indicating its potential efficacy for this aggressive cancer.

The case suggests that nab-paclitaxel could be a viable second-line treatment option for cholangiocarcinoma, warranting further investigation in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin-bound paclitaxel as new treatment for metastatic cholangiocarcinoma: A case report. Martin Huertas, R., Fuentes-Mateos, R., Serrano Domingo, JJ., et al.[2020]

In a small study of 3 patients with metastatic ampullary and duodenal adenocarcinoma who had previously failed standard chemotherapy, treatment with nab-paclitaxel and gemcitabine (with or without cisplatin) resulted in excellent tumor responses and over a year of progression-free survival.

All patients showed significant reductions in tumor markers and have survived for 2-3 years since their diagnosis, suggesting that nab-paclitaxel combined with gemcitabine could be a promising salvage therapy for these difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable response for ampullary and duodenal adenocarcinoma with a nab-paclitaxel plus gemcitabine ± cisplatin combination. Cen, P., Wray, CJ., Zhang, S., et al.[2022]

In a phase 2 trial involving 150 patients with advanced biliary cancers, the addition of cetuximab to standard chemotherapy (gemcitabine and oxaliplatin) did not significantly improve progression-free survival compared to chemotherapy alone, with median progression-free survival of 6.1 months versus 5.5 months, respectively.

While cetuximab was well tolerated, the study found a higher incidence of grade 3-4 adverse events in the cetuximab group, suggesting that the standard chemotherapy regimen should remain the preferred treatment for advanced biliary cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. Malka, D., Cervera, P., Foulon, S., et al.[2022]

In a study of 34 patients with advanced biliary tract cancer, the combination of nab-paclitaxel, gemcitabine, and cisplatin resulted in a median progression-free survival of 7.1 months and overall survival of 16.4 months, indicating promising therapeutic potential.

The treatment was associated with significant adverse effects, particularly neutropenia and leukopenia in 26.5% of patients, while biomarkers like carcinoembryonic antigen (CEA) levels and immune cell changes were identified as potential indicators of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer. Liu, T., Li, Q., Lin, Z., et al.[2023]

In a study of 27 elderly Japanese patients (aged ≥ 75) with non-curatively resectable pancreatic cancer, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed a high disease control rate of 92.6%, indicating strong efficacy in managing the disease.

Despite its effectiveness, the treatment was associated with significant adverse effects, including a 51.9% incidence of grade 3 or higher hemotoxicity and a 22% rate of grade ≥ 3 peripheral nerve disorders, highlighting the need for careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. Hasegawa, R., Okuwaki, K., Kida, M., et al.[2022]

Nab-paclitaxel, a novel formulation of paclitaxel, is water-soluble and free from toxic solvents, leading to reduced infusion-related toxicities and allowing for higher dosing compared to traditional formulations.

Clinical trials have shown that nab-paclitaxel improves overall response rates and survival outcomes while exhibiting a superior safety profile in patients with gastrointestinal cancers, leading to its FDA approval for use in metastatic pancreatic cancer and other gastrointestinal malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-Paclitaxel in the Treatment of Gastrointestinal Cancers-Improvements in Clinical Efficacy and Safety. Hassan, MS., Awasthi, N., Ponna, S., et al.[2023]

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

In a trial involving 84 patients with advanced non-small-cell lung cancer, the efficacy of weekly nab-paclitaxel plus cisplatin was found to be similar to that of gemcitabine plus cisplatin, with median progression-free survival of 4.8 months for nab-TP and 5.2 months for GP.

Nab-paclitaxel showed improved overall survival in patients with EGFR mutations (26.7 months) and those with a performance status of 0 (23.5 months) compared to gemcitabine, indicating potential benefits in specific patient subgroups while maintaining comparable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer: A phase II open-label clinical study. Qin, S., Yu, H., Wu, X., et al.[2022]

In a study involving 90 patients with advanced biliary cancer, the addition of the monoclonal antibody panitumumab to standard chemotherapy did not improve progression-free survival (PFS), overall survival (OS), or objective response rate (ORR) compared to chemotherapy alone.

The results suggest that panitumumab does not provide additional benefits for patients with KRAS wild-type biliary cancer, highlighting the importance of genetic profiling in future clinical trials to identify effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PICCA study: panitumumab in combination with cisplatin/gemcitabine chemotherapy in KRAS wild-type patients with biliary cancer-a randomised biomarker-driven clinical phase II AIO study. Vogel, A., Kasper, S., Bitzer, M., et al.[2022]

In a study of 30 patients with previously treated HER2-positive metastatic biliary tract cancer, the combination of tucatinib and trastuzumab showed a confirmed objective response rate of 46.7%, indicating significant antitumor activity.

The treatment was generally well tolerated, with common side effects including fever and diarrhea, but no deaths were attributed to treatment-related adverse events, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study. Nakamura, Y., Mizuno, N., Sunakawa, Y., et al.[2023]

In a study involving 46 patients with KRAS wild-type irresectable biliary tract cancer, combination chemotherapy with panitumumab showed a promising 74% progression-free survival rate at 6 months, indicating its potential effectiveness as a first-line treatment.

The treatment resulted in a median overall survival of 10.0 months and a manageable safety profile, suggesting that biomarker-driven patient selection can enhance treatment outcomes in biliary tract cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer. Jensen, LH., Lindebjerg, J., Ploen, J., et al.[2023]

In a study of 325 patients with advanced biliary tract cancer, those who received second-line chemotherapy had a median overall survival of 17.3 months, compared to 9.5 months for those who only received first-line treatment, indicating a significant survival benefit from second-line therapy.

Capecitabine was the most commonly used second-line treatment, and there was no significant difference in overall survival between patients receiving single-agent versus doublet second-line chemotherapy, suggesting that single-agent therapies can be effective for patients who are fit enough to continue treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use, response and outcomes of second-line chemotherapy in patients with advanced biliary tract cancers. Mathers, B., Abadi, S., Davies, JM., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase II Study of Nab-Paclitaxel and Gemcitabine as First-Line Therapy in Patients with Cholangiocarcinoma Ineligible for Cisplatin-Based Chemotherapy (NACHO). [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Albumin-bound paclitaxel as new treatment for metastatic cholangiocarcinoma: A case report. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Durable response for ampullary and duodenal adenocarcinoma with a nab-paclitaxel plus gemcitabine ± cisplatin combination. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. [2022]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Nab-Paclitaxel in the Treatment of Gastrointestinal Cancers-Improvements in Clinical Efficacy and Safety. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. [2022]

9. China pubmed.ncbi.nlm.nih.gov

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer: A phase II open-label clinical study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

PICCA study: panitumumab in combination with cisplatin/gemcitabine chemotherapy in KRAS wild-type patients with biliary cancer-a randomised biomarker-driven clinical phase II AIO study. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Use, response and outcomes of second-line chemotherapy in patients with advanced biliary tract cancers. [2023]