Durvalumab + Chemotherapy for Bile Duct Cancer

Not currently recruiting at 62 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Active infection, Pregnancy, others

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: 13

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether a combination of durvalumab, a type of immunotherapy, and standard chemotherapy (including cisplatin and gemcitabine) can shrink bile duct cancer tumors before surgery. The treatment may make it easier to remove cancerous tissue while preserving more healthy tissue. It targets patients with bile duct cancer that can be surgically removed and is considered high-risk, such as when the tumor exceeds 5 cm or has spread to nearby lymph nodes. Participants should have been diagnosed with intrahepatic cholangiocarcinoma and not received prior treatment for this condition. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to significant advancements in cancer treatment.

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 use immunosuppressive medications within 14 days before starting the trial, except for certain types of steroids. It's best to discuss your specific medications with the trial team.

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

Research has shown that combining durvalumab with gemcitabine and cisplatin may help treat cancer. In studies, this combination proved effective for many patients. However, safety remains a major concern. Reports indicate that about 31% of patients experienced serious side effects when taking durvalumab with chemotherapy. Common side effects included fever, low blood cell counts, and tiredness.

These treatments are already used for other types of cancer, indicating they are somewhat well-understood. However, the combination with durvalumab is still under study for bile duct cancer. It is crucial to discuss the risks and benefits with a doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for bile duct cancer?

Researchers are excited about the combination of durvalumab with chemotherapy for bile duct cancer because it introduces an immunotherapy component into the treatment. While standard treatments like gemcitabine and cisplatin focus on directly attacking cancer cells, durvalumab is an immune checkpoint inhibitor that helps the immune system recognize and fight cancer more effectively. This combination aims to enhance the body's natural defenses against tumors and may improve outcomes beyond what traditional chemotherapy alone can achieve.

What evidence suggests that this treatment might be an effective treatment for bile duct cancer?

In this trial, participants will receive a combination of durvalumab, gemcitabine, and cisplatin to treat biliary tract cancer. Research has shown that this combination may be effective, with one study reporting a 72% objective response rate, indicating that many patients' tumors shrank or disappeared. Typically, patients using only gemcitabine and cisplatin live for about 10–12 months. Adding durvalumab may improve these outcomes by enhancing the body's immune response against cancer cells. This combination is being studied to help make tumors smaller and easier to remove surgically. ^{1 2 3 4 6}

Who Is on the Research Team?

Hop Tran Cao, MD

Principal Investigator

University of Texas MD Anderson Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with a specific liver cancer called intrahepatic cholangiocarcinoma that can be surgically removed. They must have measurable disease, no prior treatments for this cancer, and be fit for surgery. The tumor should be larger than 5 cm or there may be regional lymph node metastases or vascular invasion.

Inclusion Criteria

I have a tumor that can be measured and is at least 1 cm in size.

A surgeon has approved me for surgery.

My bile duct cancer is confirmed and can be surgically removed.

Exclusion Criteria

Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment, Major surgical procedure (as defined by the Investigator) within 14 days prior to the first dose of durvalumab. Note: Local surgery of isolated lesions for palliative intent or biliary stents is acceptable, Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent, Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication), Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. Note: Patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab, Patients who are receiving any other investigational agents, History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab, gemcitabine, cisplatin, or other platinum-containing compounds, Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous, Pregnant women are excluded from this study because durvalumab (MEDI4736) is an anti-PD-L1 monoclonal antibody agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab, breastfeeding should be discontinued if the mother is treated with durvalumab. These potential risks may also apply to other agents used in this study. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after durvalumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately, Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of durvalumab, Patients with active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: Patients with vitiligo or alopecia, Patients with hypothyroidism (e.g. following Hashimoro syndrome) stable on hormone replacement, Any chronic skin condition that does not require systemic therapy, Patients without active disease in the last 5 years may be included but only after consultation with the study physician, Patients with celiac disease controlled by diet alone, Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA, History of allogenic organ transplantation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Therapy

Participants receive durvalumab with gemcitabine and cisplatin for 4 cycles before surgery

12 weeks

4 visits (in-person)

Surgical Resection

Participants undergo surgical resection to remove the tumor

1 week

1 visit (in-person)

Adjuvant Therapy

Participants may continue durvalumab, gemcitabine, and cisplatin regimen for up to 4 additional cycles

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months for 2 years, then every 6 months for 5 years, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Durvalumab
• Gemcitabine

Trial Overview The study tests the combination of durvalumab (a monoclonal antibody) with standard chemotherapy drugs gemcitabine and cisplatin before surgery in high risk liver cancer patients to see if it reduces the tumor size more effectively than current methods.

How Is the Trial Designed?

Group I: Treatment (durvalumab, gemcitabine, cisplatin) Experimental Treatment 8 Interventions

Patients receive durvalumab IV over 60 minutes on day 1 with gemcitabine IV over 30 minutes and cisplatin IV over 60 minutes on days 1 and 8 for 4 cycles and then undergo surgical resection on study. Following surgery, patients may continue the durvalumab, gemcitabine and cisplatin regimen for up to 4 additional cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scans and/or MRI scans and blood sample collection throughout study, as well as tissue biopsies during screening and on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Adding durvalumab to gemcitabine and cisplatin for advanced biliary tract cancer resulted in only a modest increase in quality-adjusted life years (0.12 QALY) but came with a high incremental cost, leading to an incremental cost-effectiveness ratio (ICER) of $159,644.70/QALY with charity assistance and $696,571.11/QALY without, both exceeding the willingness-to-pay threshold in China.

The analysis indicated that durvalumab would only become cost-effective if its price dropped by over 94.2%, highlighting that the high cost of durvalumab significantly impacts its economic viability as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of adding durvalumab to chemotherapy as first-line treatment for advanced biliary tract cancer based on the TOPAZ-1 trial. Zhao, Q., Xie, R., Zhong, W., 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 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 the phase 3 TOPAZ-1 trial, the combination of durvalumab with gemcitabine and cisplatin significantly improved overall survival and progression-free survival in adults with advanced biliary tract cancer, compared to the placebo group.

Durvalumab's benefits were consistent across various patient factors, including tumor location and PD-L1 expression levels, and the treatment was found to be manageable in terms of tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Advanced Biliary Tract Cancer. Fung, S., Syed, YY.[2023]

In a real-world study of 145 patients with advanced biliary tract cancer, the combination of durvalumab with gemcitabine and cisplatin achieved a median progression-free survival (PFS) of 8.9 months and a median overall survival (OS) of 12.9 months, confirming the efficacy seen in the TOPAZ-1 trial.

The treatment was associated with a high rate of adverse events (94.5%), with 35.2% experiencing severe (grades 3-4) adverse events, but only 2.1% had severe immune-mediated adverse events, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data. Rimini, M., Fornaro, L., Lonardi, S., et al.[2023]

In a phase 2 study involving 128 patients with advanced biliary tract cancer, the combination of gemcitabine and cisplatin with the immunotherapy durvalumab (and tremelimumab for some) resulted in a promising objective response rate of 66%, indicating potential efficacy as a first-line treatment.

The treatment was generally safe, with the most common severe side effects being decreased neutrophil count and anemia, but no unexpected safety events or treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study. Oh, DY., Lee, KH., Lee, DW., et al.[2023]

The Phase I trial established the maximally tolerated doses (MTD) for two drug combinations: everolimus plus gemcitabine and the three-drug regimen including cisplatin, with both regimens being generally well tolerated despite hematologic dose-limiting toxicities (DLTs).

The trial showed promising efficacy, with complete responses in two patients and partial responses in three others, suggesting that the three-drug combination could be a viable option for future studies in specific cancers like cholangiocarcinoma and gallbladder carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of everolimus, gemcitabine and cisplatin in patients with solid tumors. Costello, BA., Borad, MJ., Qi, Y., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10667376/

Durvalumab: A Review in Advanced Biliary Tract Cancer The median overall survival of patients with advanced biliary tract cancer receiving gemcitabine plus cisplatin is ≈ 10–12 months, and ...

2. 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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05655949

Y-90 With Durvalumab/Gem/Cis in Intrahepatic Cholangio This trial is designed to study a combination of interventions (chemotherapy, immunotherapy, and radiation) as a potential new treatment for bile duct ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03046862

NCT03046862 | Durvalumab(MEDI4736)/Tremelimumab in ... The combination of Durvalumab/Tremelimumab with gemcitabine/cisplatin chemotherapy is feasible and efficacious in chemo-naïve biliary tract cancer. <Purpose of ...

5. touchoncology.com touchoncology.com/gastrointestinal-cancers/journal-articles/durvalumab-for-the-treatment-of-advanced-biliary-tract-cancer/

Durvalumab for the Treatment of Advanced Biliary Tract ... The TOPAZ-1 trial introduced durvalumab, an immunotherapy drug, combined with GemCis for untreated patients with advanced BTCs.

6. imfinzihcp.com imfinzihcp.com/biliary-tract-cancers.html

Immunotherapy for Advanced Biliary Tract Cancers Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% ...