Chemotherapy for Biliary Tract Cancer

No longer recruiting at 707 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of chemotherapy drugs—gemcitabine hydrochloride and cisplatin—works better with or without the addition of nab-paclitaxel in treating metastatic biliary tract cancers. These drugs aim to stop cancer cells from growing and spreading. Suitable participants are those newly diagnosed with metastatic biliary tract cancer who have not yet received treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of cisplatin and gemcitabine has been tested in patients with biliary tract cancer, and they generally tolerate this treatment well. Common side effects include low blood cell counts, leading to tiredness or infections, but these are usually manageable.

Studies also show promising safety results for the combination of nab-paclitaxel, cisplatin, and gemcitabine. Patients receiving this combination have lived longer without serious side effects, indicating it is well-tolerated.

Both treatments have undergone earlier studies suggesting they are safe for humans. This information may reassure those considering joining a trial about the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for biliary tract cancer because they offer new combinations of chemotherapy drugs that might improve outcomes. Unlike standard treatments, which often use a single chemotherapy regimen, one arm of this trial explores the combination of cisplatin and gemcitabine hydrochloride, potentially enhancing the effectiveness by using two drugs that target cancer cells in different ways. The other arm adds nab-paclitaxel to this combination, which could further increase the potency by disrupting cancer cell division more effectively. These combinations might provide a more powerful attack on cancer cells, offering hope for better control of the disease.

What evidence suggests that this trial's treatments could be effective for biliary tract cancer?

Studies have shown that combining cisplatin and gemcitabine helps patients with biliary tract cancer live longer. Specifically, 59.3% of patients experienced no cancer growth for at least 6 months, compared to 42.5% who received only gemcitabine. In this trial, one group of participants will receive cisplatin and gemcitabine. Another group will receive an additional treatment with nab-paclitaxel alongside cisplatin and gemcitabine, which appears to improve outcomes further, helping people live longer without their cancer worsening. Overall, these treatments have demonstrated promising results in controlling cancer for a longer time. ^{1 2 6 7 8}

Who Is on the Research Team?

Rachna Shroff

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa0908721

Cisplatin plus Gemcitabine versus Gemcitabine for Biliary ... The 6-month progression-free survival rate was 59.3% in the cisplatin–gemcitabine group and 42.5% in the gemcitabine-only group. Figure 2.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4509359/

Gemcitabine Plus Cisplatin for Advanced Biliary Tract Cancer Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable.

3. ccanewsonline.com ccanewsonline.com/web-exclusives/expanding-treatment-options-for-patients-with-advanced-cholangiocarcinoma

Expanding Treatment Options for Patients with Advanced ... The results showed a median progression-free survival (PFS) of 12.9 months among the patients with intrahepatic cholangiocarcinoma and 6 months among patients ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3967-0

Adjuvant treatment of resectable biliary tract ... - BMC Cancer Based on this study, cisplatin plus gemcitabine is being considered the new practice standard for patients with inoperable biliary tract cancer.

5. nature.com nature.com/articles/6605211

Gemcitabine alone or in combination with cisplatin ... In addition, 11 patients had stable disease on gemcitabine alone vs 17 on the combination (SD 35.5 vs 47.2%) The tumour control rate (CR+PR+SD) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38823398/

Durvalumab or placebo plus gemcitabine and cisplatin in ... The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), ...

7. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2200015

Durvalumab plus Gemcitabine and Cisplatin in Advanced ... A phase 2 trial of durvalumab in combination with gemcitabine and cisplatin demonstrated promising efficacy, with an objective response rate of 72% and a ...

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2839520

Gemcitabine and Cisplatin Plus Polymeric Micellar ... The prognosis for advanced biliary tract cancer is poor, with a median overall survival (OS) of approximately 1 year. Treatment with gemcitabine ...