Rilvegostomig + Chemotherapy for Biliary Tract Cancer

(ARTEMIDE-Bil01 Trial)

Recruiting in Palo Alto (17 mi)

+168 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants

Disqualifiers: Metastatic disease, Autoimmune disorders, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called rilvegostomig to see if it can help prevent biliary tract cancer from coming back after surgery. The study includes patients who have had surgery to remove their cancer but are still at risk of it returning. Rilvegostomig will be used along with standard chemotherapy to see if this combination is more effective.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have used immunosuppressive medication within 14 days before the first dose.

What data supports the effectiveness of the drug Rilvegostomig + Chemotherapy for Biliary Tract Cancer?

Research shows that the combination of gemcitabine and cisplatin is a standard treatment for advanced biliary tract cancer, and the addition of S-1 (Tegafur/Gimeracil/Oteracil) has been explored in various studies, showing potential benefits. Additionally, S-1 has been used effectively after the failure of gemcitabine, suggesting it may enhance treatment outcomes in certain cases. ^{1 2 3 4 5}

Is the combination of Rilvegostomig and chemotherapy safe for treating biliary tract cancer?

The combination of capecitabine and oxaliplatin (CAPOX) is generally well-tolerated for advanced biliary tract cancers, with the most common severe side effect being peripheral sensory neuropathy (nerve damage causing tingling or numbness). S-1 (Tegafur Gimeracil Oteracil Potassium) can cause severe diarrhea and mouth sores, while gemcitabine-based treatments may lead to more severe blood-related side effects. Patients should discuss potential benefits and risks with their doctors. ^{1 5 6 7 8}

How is the drug Rilvegostomig + Chemotherapy different from other treatments for biliary tract cancer?

Rilvegostomig combined with chemotherapy for biliary tract cancer is unique because it potentially introduces a new mechanism of action or combination that hasn't been standard in existing treatments, which typically involve drugs like gemcitabine and cisplatin. This combination may offer a novel approach compared to the standard chemotherapy regimens currently used. ^{1 2 9 10 11}

Research Team

Eligibility Criteria

This trial is for individuals who've had surgery to remove biliary tract cancer and are now disease-free. They should have a performance status indicating they can carry out daily activities with ease or minor limitations, and must not have used immunosuppressive drugs recently, nor have autoimmune disorders, severe diseases, recent thromboembolic events, or active hepatitis infections.

Inclusion Criteria

My bile duct cancer was confirmed by a lab test and has been fully removed.

I can provide a tumor sample from my surgery.

I am fully active or can carry out light work.

Exclusion Criteria

My cancer is ampullary, neuroendocrine, mixed, or non-epithelial.

My cancer was advanced or had spread at the time of diagnosis.

I have an autoimmune or severe uncontrolled disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rilvegostomig or placebo in combination with chemotherapy as adjuvant treatment

6 months

Follow-up

Participants are monitored for recurrence-free survival and overall survival

5-7 years

Treatment Details

Interventions

• Capecitabine (Chemotherapy)
• Gemcitabine/Cisplatin (Chemotherapy)
• Rilvegostomig (Monoclonal Antibodies)
• S-1 [Tegafur/Oteracil/gimeracil] (Chemotherapy)

Trial Overview The study compares the effectiveness of Rilvegostomig plus chemotherapy against a placebo combined with chemotherapy in patients who've undergone surgery for biliary tract cancer. The goal is to see if Rilvegostomig can prevent the cancer from coming back.

Participant Groups

Group I: Arm A Experimental Treatment 4 Interventions

Rilvegostomig IV infusion + Investigator choice of chemotherapy (Capecitabine or Gemcitabine/Cisplatin or S-1)

Group II: Arm B Placebo Group 4 Interventions

Placebo IV infusion + Investigator choice of chemotherapy (Capecitabine or Gemcitabine/Cisplatin or S-1)

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

The combination of nab-paclitaxel and S-1 demonstrated a 27.5% objective response rate in patients with advanced biliary tract carcinoma, indicating significant antitumor activity, especially in gallbladder carcinoma (53.8% response).

The treatment showed a favorable safety profile, with the most common severe side effects being neutropenia and stomatitis, and median progression-free survival and overall survival were 6.0 months and 13.2 months, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) as first-line treatment for advanced biliary tract adenocarcinoma: a phase 2 clinical trial. Zhang, W., Sun, Y., Jiang, Z., et al.[2023]

In a phase I study involving 18 patients with untreated advanced biliary tract cancer, the triplet regimen of gemcitabine, cisplatin, and S-1 (GPS) was found to be safe, with dose-limiting toxicities occurring in only a few patients.

The treatment demonstrated preliminary antitumor activity, achieving a 50% response rate among 14 patients with measurable lesions, indicating potential efficacy for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer. Moriwaki, T., Ishida, H., Araki, M., 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 33 patients with relapse and unresectable biliary tract cancer treated with S-1 after failing gemcitabine, the neutrophil-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) were identified as significant poor prognostic factors for overall survival.

Changes in the PNI from the start of S-1 treatment to the end were significantly associated with therapeutic efficacy, suggesting that monitoring PNI could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of Prognostic Factors in Patients with Relapse and Unresectable Biliary Tract Cancer, Treated with S-1 after Failure of Gemcitabine]. Nakai, M., Kikkawa, A., Funahara, H., et al.[2022]

In a phase III trial involving 222 patients with metastatic biliary tract cancers, XELOX (capecitabine plus oxaliplatin) demonstrated noninferiority to GEMOX (gemcitabine plus oxaliplatin) in terms of 6-month progression-free survival, with rates of 46.7% for XELOX and 44.5% for GEMOX.

XELOX was associated with fewer hospital visits compared to GEMOX, indicating a potentially better quality of life for patients, while both treatments had similar overall survival rates and adverse event profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. Kim, ST., Kang, JH., Lee, J., et al.[2023]

In a study of 65 patients with advanced biliary system adenocarcinomas, the combination therapy of capecitabine and oxaliplatin (CAPOX) showed a 27% response rate in patients with gallbladder carcinoma (GBC) and extrahepatic cholangiocarcinoma (ECC), indicating its efficacy for these types of cancer.

The CAPOX regimen was well tolerated overall, with the most common severe side effect being peripheral sensory neuropathy in 11 patients, suggesting it is a viable treatment option for advanced GBC and ECC, but less effective for intrahepatic cholangiocarcinoma (ICC), which had no objective responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. Nehls, O., Oettle, H., Hartmann, JT., et al.[2022]

In a network meta-analysis of 16 trials with 2245 patients, the combination of Gemcitabine and S-1 (GS) showed superior efficacy in terms of overall survival and response rates compared to standard treatments like Fluorouracil (FU).

While GS and other combinations like Cap plus CIS (CapC) demonstrated better response rates, they also had higher incidences of severe side effects, highlighting the need for careful consideration of both efficacy and toxicity when choosing treatment options for advanced biliary tract cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of First-line Chemotherapies for Advanced Biliary Tract Cancer: A Network Meta-analysis. Zheng, W., Ying, J., Zhou, Y., et al.[2020]

In a study of 51 patients with advanced biliary tract cancer, combination chemotherapy with S-1 and cisplatin resulted in a 30% overall response rate, with a median overall survival of 8.7 months.

The treatment was associated with manageable toxicity, including grade 3/4 neutropenia occurring in 8.9% of cycles, indicating that while the regimen is effective, it also requires monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of S-1 and cisplatin in patients with metastatic or relapsed biliary tract cancer. Kim, YJ., Im, SA., Kim, HG., et al.[2020]

References

1. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) as first-line treatment for advanced biliary tract adenocarcinoma: a phase 2 clinical trial. [2023]

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

Randomised, Phase II study of selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer. [2023]

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

Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer. [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. Japan pubmed.ncbi.nlm.nih.gov

[Evaluation of Prognostic Factors in Patients with Relapse and Unresectable Biliary Tract Cancer, Treated with S-1 after Failure of Gemcitabine]. [2022]

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

Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. [2023]

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

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of First-line Chemotherapies for Advanced Biliary Tract Cancer: A Network Meta-analysis. [2020]

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

A phase II trial of tegafur-uracil plus leucovorin (LV) in the treatment of advanced biliary tract carcinomas. [2019]

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

The Efficacy of Different Chemotherapy Regimens for Advanced Biliary Tract Cancer: A Systematic Review and Network Meta-Analysis. [2020]

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

A phase II trial of S-1 and cisplatin in patients with metastatic or relapsed biliary tract cancer. [2020]