Chemotherapy for Biliary Tract Cancer

Recruiting at 691 trial locations

Overseen By Dana Sparks

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Southwest Oncology Group

Disqualifiers: Ampullary cancer, Prior systemic therapy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 27

Duration: Up to 3 years

452 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing how well two cancer-fighting drugs work together, and whether adding a third drug makes them more effective in treating patients with advanced biliary tract cancers. The drugs aim to kill cancer cells, stop them from dividing, or prevent them from spreading.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves chemotherapy, it's important to discuss your current medications with the trial team to ensure there are no interactions.

What data supports the effectiveness of this drug for biliary tract cancer?

Research shows that the combination of gemcitabine and cisplatin is the standard first-line chemotherapy for advanced biliary tract cancer, with studies indicating it is more effective than gemcitabine alone. ^{1 2 3 4 5}

Is the combination of gemcitabine and cisplatin safe for humans?

The combination of gemcitabine and cisplatin has been studied for safety in patients with biliary tract cancer, showing it is generally safe for use in humans, although specific side effects and tolerability can vary. ^{2 3 6 7 8}

What makes the chemotherapy drug combination of Cisplatin and Gemcitabine unique for treating biliary tract cancer?

The combination of Cisplatin and Gemcitabine is unique because it has been the standard first-line chemotherapy for advanced biliary tract cancer for over a decade, offering a well-established treatment option when few others exist. This combination is particularly notable for its use in both palliative care and after surgical removal of the cancer, providing flexibility in treatment approaches. ^{1 4 9 10 11}

Research Team

Rachna Shroff

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with newly diagnosed advanced biliary tract cancers, including gallbladder and bile duct cancers. Participants must not have had previous systemic therapy for their cancer or adjuvant therapy within the last 6 months. They should be in good physical condition (Zubrod performance status of 0 or 1) and cannot have a history of significant peripheral neuropathy or other active cancers, except certain treated skin cancers and early-stage cured cancers.

Inclusion Criteria

I haven't had additional cancer treatment in the last 6 months.

I do not have a diagnosis of ampullary cancer.

I haven't had systemic therapy for my advanced biliary cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive chemotherapy with gemcitabine hydrochloride and cisplatin, with or without nab-paclitaxel, on days 1 and 8 of each 21-day cycle

Up to 3 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Every 6 months for 2 years, then at the end of year 3

Every 6 months

Treatment Details

Interventions

• Cisplatin
• Gemcitabine Hydrochloride
• Nab-paclitaxel

Trial Overview The study is testing how well gemcitabine hydrochloride and cisplatin work when given together compared to when they are combined with nab-paclitaxel in treating advanced biliary tract cancers. The goal is to determine if adding nab-paclitaxel improves treatment outcomes.

Participant Groups

Group I: Arm II (cisplatin, gemcitabine hydrochloride) Experimental Treatment 2 Interventions

Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (nab-paclitaxel, cisplatin, gemcitabine hydrochloride) Experimental Treatment 3 Interventions

Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days 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?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A comprehensive analysis of 161 trials involving 6,337 patients found that the standard gemcitabine platinum (GP) chemotherapy has a median overall survival of 9.5 months and a tumor control rate of 63.5%.

Newer treatment regimens, including triplet combinations of gemcitabine, fluoropyrimidine, and platinum (GFP) or gemcitabine with targeted therapies, showed significantly better tumor control and overall survival compared to the standard GP regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Eckel, F., Schmid, RM.[2022]

In a study of 29 patients with unresectable biliary tract cancer, the combination therapy of gemcitabine (GEM) and cisplatin (CDDP) demonstrated a disease control rate of 66.7%, indicating its effectiveness as a treatment option.

The therapy was found to be safe, with manageable adverse effects; the most common severe hematological toxicity was neutropenia (65.5%), but there were no cases of interstitial pneumonia reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[GEM plus CDDP Combination Therapy for Unresectable Biliary Tract Cancer-A Single Institution Experience]. Muneta, M., Ohmura, Y., Takeda, Y., et al.[2023]

A meta-analysis of 5 studies involving 727 patients found that fluoropyrimidine-cisplatin (FP) is as effective as gemcitabine-cisplatin (GP) for treating advanced biliary tract cancer, with no significant differences in overall response rate, disease control rate, or overall survival.

FP demonstrated a significantly lower incidence of severe adverse events (grade 3/4) compared to GP, indicating a more favorable safety profile for FP in first-line chemotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between Fluoropyrimidine-Cisplatin and Gemcitabine-Cisplatin as First-Line Chemotherapy for Advanced Biliary Tract Cancer: A Meta-Analysis. Zheng, T., Jin, J., Zhou, L., 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 43 patients with unresectable biliary tract cancer, the combination of gemcitabine and cisplatin showed an overall response rate of 27.5%, indicating it has potential efficacy in treating this difficult-to-treat cancer.

The treatment was generally well-tolerated, with manageable side effects, including low rates of severe hematologic toxicity, suggesting that gemcitabine plus cisplatin could be a safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. Thongprasert, S., Napapan, S., Charoentum, C., et al.[2022]

In a phase I study involving 12 patients with unresectable advanced biliary tract cancer, the combination of gemcitabine, cisplatin, and oral S-1 was found to be safe, with no dose-limiting toxicities reported.

The recommended doses of S-1 were established at 80, 100, and 120 mg per day based on patient body surface area, and one patient even achieved conversion to curative surgery, indicating potential efficacy of the treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of S-1 every other day in combination with gemcitabine/cisplatin for inoperable biliary tract cancer. Uwagawa, T., Sakamoto, T., Abe, K., et al.[2022]

In a study of 29 patients with biliary tract cancer, the combination therapy of gemcitabine and cisplatin was found to be tolerable, with 72% of patients completing the treatment protocol despite some experiencing significant side effects like leukopenia and neutropenia.

The two-year recurrence-free survival rate was 59% and the overall survival rate was 90%, suggesting that this treatment regimen may be effective in improving survival outcomes for patients after curative resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and efficacy of gemcitabine plus cisplatin combination therapy after curative resection for biliary tract cancer. Kainuma, O., Miura, F., Furukawa, D., et al.[2022]

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

Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

[GEM plus CDDP Combination Therapy for Unresectable Biliary Tract Cancer-A Single Institution Experience]. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison between Fluoropyrimidine-Cisplatin and Gemcitabine-Cisplatin as First-Line Chemotherapy for Advanced Biliary Tract Cancer: A Meta-Analysis. [2022]

5. 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]

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

Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Phase I trial of S-1 every other day in combination with gemcitabine/cisplatin for inoperable biliary tract cancer. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

A Multicenter Phase II Study of Gemcitabine plus S-1 Chemotherapy for Advanced Biliary Tract Cancer. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

Feasibility and efficacy of gemcitabine plus cisplatin combination therapy after curative resection for biliary tract cancer. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Changing Landscape of Systemic Therapy in Biliary Tract Cancer. [2023]

11. England pubmed.ncbi.nlm.nih.gov

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