Drug Combination for Biliary Tract Cancer
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Nataliya Uboha
Must not be taking: Immune checkpoint inhibitors
Disqualifiers: Autoimmune disease, Transplantation, CNS metastasis, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is a phase 2 study of gemcitabine, cisplatin, zimberelimab (AB122) and quemliclustat (AB680) in subjects with untreated advanced biliary tract cancers (BTC). The study will include a safety run-in involving 6 study participants. The goal of the safety run-in is to screen for early safety signals of the proposed drug combination. Trial enrollment can continue while full safety assessment is being completed for the first 6 subjects.
Participants will receive 4 cycles of combination therapy as described. After 4 cycles (\~6 months), cisplatin will be discontinued, while gemcitabine, zimberelimab (AB122), and quemliclustat (AB680) will be continued. Subjects will be treated until disease progression or development of intolerable toxicities. In total, there will be up to 39 participants on the study.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, if you are on treatments for active autoimmune diseases or have had recent major surgery, you may need to discuss this with the trial team.
What data supports the effectiveness of the drug combination for biliary tract cancer?
Research shows that combining gemcitabine and cisplatin is a standard treatment for advanced biliary tract cancer, and adding other drugs like durvalumab or pembrolizumab can improve outcomes. These combinations have been shown to prolong survival and manage the disease more effectively.
12345What safety data exists for the drug combination used in biliary tract cancer treatment?
The combination of cisplatin and gemcitabine has been used as a standard treatment for advanced biliary tract cancer. Safety data shows that while it can be effective, it may cause significant side effects like neutropenia (low white blood cell count), thrombocytopenia (low platelet count), and anorexia (loss of appetite), requiring careful monitoring and sometimes dose adjustments.
36789What makes the drug combination for biliary tract cancer unique?
This drug combination is unique because it includes Quemliclustat and Zimberelimab, which are not part of the standard gemcitabine and cisplatin treatment for biliary tract cancer. These additional drugs may offer a novel approach by potentially enhancing the immune response and targeting cancer cells more effectively.
23101112Eligibility Criteria
Adults with advanced biliary tract cancers who haven't had systemic treatment for it can join. They must have measurable disease, good organ function, and no recent major surgeries or untreated brain metastasis. Participants need to be able to follow the study plan and use effective birth control if they can have children.Inclusion Criteria
I haven't had systemic treatment for my advanced disease, but I may have had adjuvant therapy if my disease came back 6 months or more after finishing all treatments.
I understand and can follow the study's procedures.
I have been mostly active and able to care for myself in the last 28 days.
+8 more
Exclusion Criteria
Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study
I have been treated with gemcitabine, cisplatin, or immune checkpoint inhibitors for bile duct cancer.
I have not had major surgery or serious injury in the last 28 days.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Safety Run-in
Initial safety assessment involving 6 participants to screen for early safety signals of the drug combination
6 months
Multiple visits as per cycle schedule
Treatment
Participants receive 4 cycles of combination therapy with gemcitabine, cisplatin, zimberelimab, and quemliclustat. After 4 cycles, cisplatin is discontinued, and other drugs are continued until disease progression or intolerable toxicities
6 months
Day 1, 8, 22, and 29 of each cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 years
Participant Groups
The trial is testing a combination of gemcitabine, cisplatin, zimberelimab (AB122), and quemliclustat (AB680) in patients with advanced biliary tract cancers. It starts with a safety check on the first 6 people before continuing up to 39 participants who will receive these drugs until their disease worsens or side effects become too much.
1Treatment groups
Experimental Treatment
Group I: Arm AExperimental Treatment4 Interventions
Quemliclustat (AB680), zimberelimab (AB122), gemcitabine, and cisplatin in subjects with untreated advanced BTC. Quemliclustat IV: Day 1, 15, and 29 of each cycle; Zimberelimab IV: Day 1 and 22 of each cycle; Gemcitabine IV: Day 1, 8, 22 and 29 of each cycle; Cisplatin IV: Day 1, 8, 22 and 29 of Cycles 1-4 only.
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:
Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN
University of Michigan Health SystemAnn Arbor, MI
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ
University of WisconsinMadison, WI
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Who Is Running the Clinical Trial?
Nataliya UbohaLead Sponsor
Arcus Biosciences, Inc.Industry Sponsor
Gilead SciencesIndustry Sponsor
University of Wisconsin, MadisonCollaborator
References
Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. [2023]Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer.
Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. [2022]Gemcitabine plus a platinum-based agent (eg, cisplatin or oxaliplatin) is the standard of care for advanced biliary cancers. We investigated the addition of cetuximab to chemotherapy in patients with advanced biliary cancers.
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]Cisplatin and gemcitabine (CisGem) are standard chemotherapy for advanced biliary tract cancer (BTC). The MEK inhibitor selumetinib showed synergy with gemcitabine when administered sequentially in BTC. This randomised Phase 2 trial aimed to assess the efficacy of sequential or continuous selumetinib with CisGem.
A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. [2022]Current data suggest that chemotherapy combinations may be superior to single agents in biliary tract cancer. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan.
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.
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.
Initial safety and efficacy of cisplatin and gemcitabine combination chemotherapy for unresectable biliary tract cancer. [2022]Cisplatin and gemcitabine combination chemotherapy has emerged as the standard treatment for advanced or recurrent biliary tract cancer and has been used in Japan since August 2011. We retrospectively reviewed and evaluated the toxicity and compliance of this combination chemotherapy from electronic medical records. From November 2011 to June 2012, 10 patients with unresectable biliary tract cancer underwent cisplatin and gemcitabine combination chemotherapy at our hospital. Grade 3/4 toxicities of neutropenia and thrombocytopenia were observed in 5 and 4 cases, respectively. Febrile neutropenia was observed in 3 cases. Grade 2 or worse anorexia was relatively common. Dose delays and reductions due to adverse events were needed in 8 patients. Cisplatin and gemcitabine combination chemotherapy for advanced biliary tract cancer can be safely performed with careful attention given to possible hematological toxicity and anorexia.
A pilot study of concurrent chemoradiotherapy with gemcitabine and cisplatin in patients with locally advanced biliary tract cancer. [2022]Combination chemotherapy with gemcitabine and cisplatin is a standard treatment for patients with advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of gemcitabine- and cisplatin-based concurrent chemoradiotherapy in patients with unresectable biliary tract cancer.
A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer. [2023]Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients.
Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. [2022]In biliary tract cancer, gemcitabine platinum (GP) doublet palliative chemotherapy is the current standard treatment. The aim of this study was to analyze recent trials, even those small and nonrandomized, and identify superior new regimens.
Comparison between Fluoropyrimidine-Cisplatin and Gemcitabine-Cisplatin as First-Line Chemotherapy for Advanced Biliary Tract Cancer: A Meta-Analysis. [2022]Gemcitabine-cisplatin (GP) has been regarded as standard first-line chemotherapy for advanced biliary tract cancer (BTC). Fluoropyrimidine-cisplatin (FP) has also shown a survival benefit. However, the clinical choice between them is controversial.
Fixed-dose-rate gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas. [2022]Biliary tract cancers (BTC) have a poor prognosis, and there is no consensus on the best chemotherapy regimen. This study determined the response rate for fixed-dose-rate (FDR) gemcitabine combined with cisplatin.