Combination Therapy for Bile Duct Cancer

(NEOLANGIO Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Unresectable tumor, Metastatic disease, Immunodeficiency, others

Stay on Your Current Meds You can continue your current medications while participating

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: 6

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Biliary tract cancer is a highly aggressive and heterogeneous group of gastrointestinal cancers that arise from the intra- or extrahepatic bile ducts (CCA), or the gallbladder (GBC)(1-3). While it accounts for only 0.7% of all malignant tumors and 3% of all gastrointestinal malignancies in adults, both incidence and mortality are increasing. Biliary tract cancers usually present at an advanced stage, with only approximately 20% of patients being diagnosed with an early-stage disease (1, 2, 4). There is a high risk of recurrence post curative radical resection, with 60-70% of patients recurring within 5 years, with 5-year survival of around 25% (1, 2, 5). There is evidence for use of adjuvant chemotherapy with fluoropyrimidine- based regimens as per the BILCAP and ASCOT phase III trials \[(5-7).However, despite advances in adjuvant treatment, recurrence rates after resection of BTC remain high even with adjuvant chemotherapy. For example, in the BILCAP study, 5-year RFS was reported as 33.9% (95% CI: 27.6 to 40.2) (1). Therefore, an unmet need exists to optimize peri-operative treatment to reduce recurrence and improve outcomes in patients with resectable BTC.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain cancer treatments or investigational drugs. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug combination Gemcitabine/Cisplatin/Nab-Paclitaxel for bile duct cancer?

Research shows that Gemcitabine combined with Cisplatin is a standard treatment for advanced bile duct cancer, and adding Nab-Paclitaxel may enhance the effectiveness of Gemcitabine. Studies have also shown that this combination can help in cases where surgery is not initially possible, improving outcomes for some patients. ^{1 2 3 4 5}

Is the combination therapy for bile duct cancer safe for humans?

The combination of gemcitabine, cisplatin, and nab-paclitaxel has been studied for safety in patients with advanced biliary tract cancer, showing a manageable safety profile in clinical trials. ^{1 2 6 7 8}

What makes the combination therapy for bile duct cancer unique?

This treatment combines gemcitabine, cisplatin, and nab-paclitaxel with Rilvegostomig, a novel drug, potentially offering a new approach for patients who may not respond well to standard treatments. Nab-paclitaxel has shown promise in enhancing the effectiveness of gemcitabine in other cancers, suggesting a potential benefit in bile duct cancer as well. ^{1 4 5 9 10}

Eligibility Criteria

This trial is for patients with a type of bile duct cancer known as iCCA that can be surgically removed. Participants must have not undergone any previous treatments for their condition and should be physically fit enough to handle surgery and chemotherapy.

Inclusion Criteria

I am able to understand and sign the consent form.

I have not had chemotherapy, targeted therapy, or immunotherapy before.

Estimated life expectancy >3 months

Exclusion Criteria

I have another cancer that is getting worse or was treated in the last 2 years.

My cancer cannot be removed by surgery or has spread to other parts of my body.

I am currently being treated for an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 2 cycles of Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig prior to surgery

6 weeks

2 visits (in-person, every 3 weeks)

Surgical Resection

Participants undergo surgical resection of the tumor

Adjuvant Treatment

Post-surgical resection, participants receive 4 cycles of Gemcitabine/Cisplatin and Rilvegostomig

12 weeks

4 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for survival and adverse events

Until end of study

Treatment Details

Interventions

• Gemcitabine/Cisplatin/Nab-Paclitaxel
• Rilvegostomig

Trial Overview The study tests a combination of chemotherapy drugs (Gemcitabine, Cisplatin, Nab-Paclitaxel) with an investigational drug called Rilvegostomig in patients undergoing surgery for iCCA. The goal is to see if this regimen can prevent the cancer from coming back.

Participant Groups

Group I: Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

Hamilton Health Sciences Corporation

Collaborator

Trials

380

Recruited

345,000+

Findings from Research

Gemcitabine (Gem)-based combination chemotherapy significantly improves disease response rates and overall survival in patients with advanced biliary tract cancer, based on a meta-analysis of seven randomized trials involving 858 patients.

While Gem-based therapies show better efficacy, they are associated with a higher risk of severe hematological toxicities, such as leukopenia and anemia, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gemcitabine-based chemotherapies in biliary tract cancer: a meta-analysis. Liu, H., Zhang, QD., Li, ZH., 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]

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]

In the safety run-in of the IMMUNOBIL PRODIGE 57 trial involving 20 patients, the combination of durvalumab and tremelimumab with paclitaxel resulted in a high rate of dose-limiting toxicities (50%), including serious anaphylactic reactions and other severe adverse events.

Due to the safety concerns raised by the combination therapy, the trial will proceed with only the durvalumab and tremelimumab combination, indicating that the addition of paclitaxel may not be safe for patients with advanced biliary tract carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. Boilève, A., Hilmi, M., Gougis, P., et al.[2021]

In a phase II study involving 38 patients with unresectable or metastatic biliary tree carcinoma, the combination of gemcitabine and cisplatin showed an overall response rate of 32%, with one complete response and 11 partial responses, indicating its efficacy in treating this type of cancer.

The treatment was generally well-tolerated, with mild side effects and only a few cases of severe toxicity, suggesting that the GEM/CDDP regimen is a safe and reasonable option for palliative care in advanced biliary tree carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM). Giuliani, F., Gebbia, V., Maiello, E., 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]

The combination of nab-paclitaxel and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., et al.[2022]

References

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

Nab-Paclitaxel and Gemcitabine as First-line Treatment of Advanced or Metastatic Cholangiocarcinoma: A Phase 2 Clinical Trial. [2022]

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

Efficacy and safety of gemcitabine-based chemotherapies in biliary tract cancer: a meta-analysis. [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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Successful conversion surgery for locally advanced gallbladder cancer after gemcitabine and nab-paclitaxel chemotherapy. [2022]

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

Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. [2021]

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

Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM). [2022]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma. [2022]

10. Greece pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. [2022]