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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for bile duct cancer, specifically after surgery has removed the tumor. It examines how effectively this treatment can prevent cancer recurrence. The trial uses Gemcitabine, Cisplatin, Nab-Paclitaxel, and Rilvegostomig (an experimental treatment) together. Suitable participants have bile duct cancer completely removed by surgery and have not received prior cancer treatments. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that the combination of gemcitabine, cisplatin, and nab-paclitaxel has been tested for safety in patients with advanced biliary tract cancer. Results indicate that this combination is generally manageable for patients, meaning that while some side effects may occur, they usually aren't severe enough to halt treatment.

Specific safety data for rilvegostomig isn't available in the sources. However, its presence in a Phase 2 trial suggests that earlier tests have demonstrated some level of safety. Phase 2 studies typically assess how well patients tolerate the treatment and gather more information about its effectiveness.

While experimental treatments always carry some risk, this combination has been studied enough to suggest it is reasonably safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination therapy of Gemcitabine, Cisplatin, Nab-Paclitaxel, and Rilvegostomig for bile duct cancer because it brings a fresh approach to treatment. Unlike the standard chemotherapy options like Gemcitabine and Cisplatin alone, this experimental combination includes Nab-Paclitaxel, which is a nanoparticle formulation of the chemotherapy drug paclitaxel. This formulation enhances drug delivery to tumors. Additionally, Rilvegostomig is a novel component that may offer a new mechanism of action, potentially boosting the overall effectiveness by targeting the cancer cells more precisely. This combination could lead to better outcomes by increasing the effectiveness of chemotherapy while possibly reducing side effects.

What evidence suggests that this trial's treatments could be effective for bile duct cancer?

Studies have shown that gemcitabine with cisplatin is a common treatment for advanced bile duct cancer. Adding nab-paclitaxel to this regimen might enhance its effectiveness. This trial will evaluate the combination of gemcitabine, cisplatin, and nab-paclitaxel with a drug called rilvegostomig. Research suggests that this combination shows promise for treating high-risk bile duct cancer. In earlier studies, this combination led to better patient outcomes, indicating it might help prevent cancer recurrence. These findings offer hope for improving survival rates for those facing this aggressive cancer. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

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.

Estimated life expectancy >3 months

Patients with HCV infection must have management of this disease per local institutional practice

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.

Pregnancy, breastfeeding, or unwillingness to employ highly effective birth control for specified durations

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03579771

Study Details | NCT03579771 | Gemcitabine, Cisplatin, and ... This phase II trial studies how well gemcitabine, cisplatin, and nab-paclitaxel work before surgery in treating participants with high-risk bile duct cancer ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12192356/

Therapeutic Advances in Initially Unresectable Locally ... A recent multi-institutional, phase II trial evaluating neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel (NEO-GAP) for resectable high- ...

3. ctv.veeva.com ctv.veeva.com/study/gemcitabine-cisplatin-nab-paclitaxel-and-rilvegostomig-in-resectable-icca

Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig in ... This is a phase II, open-label multi-centre study to assess efficacy of Gemcitabine/Cisplatin/Nab-Paclitaxel and Rilvegostomig treatment in pre- ...

4. ccanewsonline.com ccanewsonline.com/issues/2022/september-2022-vol-3-no-3/neoadjuvant-gemcitabine-cisplatin-nab-paclitaxel-for-resectable-high-risk-icca-neo-gap

Neoadjuvant Gemcitabine/Cisplatin/Nab-Paclitaxel for ... A novel bispecific antibody, rilvegostomig, combined with chemotherapy shows promising efficacy and safety in improving outcomes for patients with advanced ...

5. withpower.com withpower.com/trial/phase-2-cholangiocarcinoma-11-2024-bc981

Combination Therapy 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39671534/

SWOG S1815: A Phase III Randomized Trial of Gemcitabine ... SWOG S1815 was a randomized, open label phase III trial, evaluating gemcitabine, nab-paclitaxel, and cisplatin (GAP) versus gemcitabine and cisplatin (GC)