Durvalumab + Chemotherapy for Bile Duct Cancer
Recruiting in Palo Alto (17 mi)
+50 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Immunosuppressants, Live vaccines
Disqualifiers: Autoimmune disorders, Active infection, Pregnancy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial tests how well giving durvalumab with standard chemotherapy, gemcitabine and cisplatin, before surgery works in treating patients with high risk liver cancer (cholangiocarcinoma) that can be removed by surgery (resectable). Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving durvalumab with gemcitabine and cisplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed in patients with high risk resectable cholangiocarcinoma.
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.
What data supports the effectiveness of the drug combination Durvalumab, Gemcitabine, and Cisplatin for bile duct cancer?
Research shows that adding Durvalumab to Gemcitabine and Cisplatin significantly improves survival in patients with advanced bile duct cancer, as seen in the TOPAZ-1 trial. This combination is now a valuable treatment option for this condition.
12345Is the combination of Durvalumab, Gemcitabine, and Cisplatin safe for humans?
The combination of Durvalumab, Gemcitabine, and Cisplatin has been studied in patients with advanced biliary tract cancer, and the safety profile was found to be manageable. This means that while there may be side effects, they are generally considered acceptable and can be managed with medical care.
12467What makes the drug combination of Durvalumab, Cisplatin, and Gemcitabine unique for bile duct cancer?
This drug combination is unique because it includes Durvalumab, an immunotherapy that blocks a protein called PD-L1, helping the immune system fight cancer more effectively. In studies, this combination has shown to significantly improve survival in patients with advanced bile duct cancer compared to the standard chemotherapy alone.
12689Eligibility Criteria
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.
High-risk iCCA is defined as the presence of any of these factors: Tumor size > 5 cm, Multifocality or satellitosis limited to the same lobe, Vascular invasion, Suspected or confirmed (via biopsy) regional lymph node metastases, Suspected is defined as lymph nodes that are deemed suspicious for metastasis based on large size (criteria vary per anatomical location; 6-10 mm for abdominal and 8-10 mm for pelvic), enhancement pattern, and shape. These may also include lymph nodes that display fludeoxyglucose F 18 (FDG)-avidity on positron emission tomography (PET) scan, if obtained, in the course of disease work-up (not mandatory), CA 19-9 > 200 U/mL, Patients are treatment naïve for iCCA, Age ≥ 18 years, Body weight > 30 kg, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Karnofsky ≥ 70%), Leukocytes ≥ 3,000/mcL, Hemoglobin ≥ 9.0 g/dL, Absolute neutrophil count ≥ 1,500/mcL, Platelets ≥ 100,000/mcL, Neuropathy grade ≤ 1 by CTCAE, Albumin ≥ 2.8 g/dL, Serum bilirubin 1.5 x institutional upper limit of normal (ULN), Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 3 × institutional ULN, Serum creatinine ≤ 1 x institutional ULN, Measured creatinine clearance > 60 mL/min or glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2 (by the Cockcroft-Gault equation), Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients, Life expectancy ≥ 12 weeks, Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial, For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated, Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured, Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression, Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial, Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better, Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
+1 more
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.
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (durvalumab, gemcitabine, cisplatin)Experimental Treatment8 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Cincinnati Cancer Center-UC Medical CenterCincinnati, OH
University of Cincinnati Cancer Center-West ChesterWest Chester, OH
University of Wisconsin Carbone Cancer Center - University HospitalMadison, WI
Vanderbilt University/Ingram Cancer CenterNashville, TN
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Durvalumab: A Review in Advanced Biliary Tract Cancer. [2023]Durvalumab (Imfinzi®), a therapeutic human monoclonal antibody which binds to and blocks the activity of the immunosuppressive programmed death-ligand 1 (PD-L1) protein, is approved in the USA, EU, Japan and other countries in combination with gemcitabine and cisplatin for adults with advanced biliary tract cancer. In the pivotal phase 3 TOPAZ-1 trial, durvalumab plus gemcitabine and cisplatin significantly prolonged overall survival and progression-free survival compared with placebo plus gemcitabine and cisplatin in adults with advanced biliary tract cancer. Benefit from durvalumab was seen irrespective of primary tumour location, disease status at diagnosis (unresectable or recurrent), or initial levels of PD-L1 expression. The tolerability of durvalumab plus gemcitabine and cisplatin was manageable. Overall, the addition of durvalumab to gemcitabine and cisplatin is a valuable new treatment option for adults with advanced biliary tract cancer.
Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data. [2023]The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real-world setting.
[GEM plus CDDP Combination Therapy for Unresectable Biliary Tract Cancer-A Single Institution Experience]. [2023]Since a randomized phase Ⅲ trial conducted in the UK in 2009 showed the superiority of gemcitabine (GEM)plus cisplatin(CDDP)combination therapy over GEM monotherapy, GEM plus CDDP combination therapy has been first-line chemotherapy for unresectable biliary tract cancer.
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]The aim of the study was to test the clinical efficacy and toxicity profile of gemcitabine (GEM) in combination with cisplatin (CDDP) in a series of patients affected by unresectable and/or metastatic biliary tree carcinoma (BTC) previously untreated with chemotherapy.
Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. [2022]The prognosis for patients with unresectable biliary tract cancer is poor and existing chemotherapy is relatively ineffective. Therefore, a need exists for new, effective chemotherapeutic regimens. The aim of this study was to determine the efficacy and safety profile of gemcitabine plus cisplatin in patients with unresectable biliary tract cancer (cholangiocarcinoma) and gall bladder cancer.
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]The IMMUNOBIL PRODIGE 57 trial is a non-comparative randomized phase II study assessing the efficacy and safety of the durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) combination with or without weekly paclitaxel in patients with advanced biliary tract carcinoma (BTC) after failure of platinum-based chemotherapy. Taxanes have already been safely combined with immune checkpoint inhibitors in other tumors. We report results of the 20-patient safety run-in.
Phase I trial of everolimus, gemcitabine and cisplatin in patients with solid tumors. [2022]A Phase I trial of the 2-drug regimen of everolimus plus gemcitabine (Cohort I) and the 3-drug regimen of everolimus plus gemcitabine and cisplatin (Cohort II) was performed to determine the maximally tolerated dose (MTD) of both combinations. An expansion cohort (Cohort III) of patients with cholangiocarcinoma or gallbladder carcinoma was treated at the MTD.
Cost-effectiveness analysis of adding durvalumab to chemotherapy as first-line treatment for advanced biliary tract cancer based on the TOPAZ-1 trial. [2023]Durvalumab plus gemcitabine and cisplatin has a significant clinical benefit for advanced biliary tract cancer (BTC). However, the high price of durvalumab warrants an exploration of the economics.
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. [2023]Immunotherapies have shown clinical activity in patients with advanced biliary tract cancer, for which outcomes remain poor despite standard of care treatment with gemcitabine and cisplatin. We aimed to evaluate gemcitabine and cisplatin plus durvalumab with or without tremelimumab as first-line treatment in patients with advanced biliary tract cancer.