Radioembolization + Immunotherapy for Bile Duct Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Mayo Clinic
Must not be taking: Immunosuppressants, Anticancer vaccines
Disqualifiers: Autoimmune disorders, Uncontrolled hypertension, HIV, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase I trial tests the safety and side effects of yttrium-90 (Y90) radioembolization combined with immunotherapy drugs tremelimumab and durvalumab in treating patients with intrahepatic cholangiocarcinoma (cancer of the bile ducts in the liver) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) who are not candidates for curative therapy or that has spread from where it first started (primary side) to multiple other places in the body (oligo-metastatic). Cholangiocarcinoma is a rare but aggressive cancer with limited curative options outside of surgery. Immunotherapy has shown modest benefit in hepatobiliary (liver, bile ducts, and gallbladder) cancers including cholangiocarcinoma. Radioembolization is a type of radiation therapy used to treat liver cancer that is advanced or has come back where tiny beads that hold the radioactive substance (radioisotope) yttrium Y90 are injected into or near the hepatic artery (the main blood vessel that carries blood to the liver). The beads collect in the tumor and the Y90 gives off radiation. This destroys the blood vessels that the tumor needs to grow and kills the tumor cells. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving Y90 radioembolization in combination with tremelimumab and durvalumab immunotherapy may be safe and beneficial in treating patients with locally advanced, unresectable or oligo-metastatic intrahepatic cholangiocarcinoma who are not candidates for curative therapy.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 14 days before joining the trial, except for certain low-dose steroids and local steroid treatments.
What data supports the effectiveness of the drug combination of durvalumab and tremelimumab for bile duct cancer?
The combination of durvalumab and tremelimumab has been approved for use in other cancers, such as unresectable hepatocellular carcinoma, where it showed improved survival rates compared to another treatment. This suggests potential effectiveness in treating bile duct cancer as well.
12345Is the combination of radioembolization and immunotherapy safe for humans?
The combination of tremelimumab and durvalumab has been studied in various cancers, showing common side effects like rash, fatigue, and diarrhea. In a study for gastric cancer, serious side effects were mostly related to chemotherapy, not the immunotherapy drugs. Overall, these treatments have been used safely in humans, but side effects can occur.
24678How is the drug combination of durvalumab and tremelimumab unique for bile duct cancer?
The combination of durvalumab and tremelimumab is unique for bile duct cancer because it uses two immune checkpoint inhibitors to enhance the body's immune response against cancer cells, which is different from traditional chemotherapy. This approach is novel as it targets specific pathways (PD-L1 and CTLA4) to boost the immune system's ability to fight cancer.
1391011Eligibility Criteria
This trial is for adults over 18 with locally advanced, unresectable intrahepatic cholangiocarcinoma who can't have curative therapy. They should be in good physical condition (ECOG PS 0 or 1), not pregnant, and without severe concurrent diseases or a history of multiple treatments for this cancer.Inclusion Criteria
International normalized ratio (INR) =< 1.6. Note: INR prolongation due (=< 14 days prior to registration)
Platelet count >= 75,000/mm^3 (=< 14 days prior to registration)
Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 5 x ULN (=< 14 days prior to registration)
+17 more
Exclusion Criteria
ALBI grade > 2
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
I have had cancer before, but it was a different type than my current diagnosis.
+43 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Patients receive transarterial Y90 radioembolization and immunotherapy drugs tremelimumab and durvalumab. Cycles repeat every 28 days for up to 24 cycles.
Up to 24 months
Monthly visits for treatment administration
Follow-up
Participants are monitored for safety and effectiveness after treatment completion.
24 months
Every 3 months
Participant Groups
The trial tests Y90 radioembolization combined with two monoclonal antibodies, tremelimumab and durvalumab. It aims to see if this combination is safe and effective at killing more tumor cells in patients who cannot undergo surgery.
2Treatment groups
Experimental Treatment
Group I: Cohort II: (Y90, tremelimumab on day 14, cycle 1, durvalumab )Experimental Treatment9 Interventions
Patients receive transarterial Y90 radioembolization on day 1 of cycle 1 and receive tremelimumab IV over 1 hour on day 14 of cycle 1 and durvalumab IV over 1 hour on day 14 of each cycle. Cycles repeat every 42 days for cycle 1 and then every 28 days for cycles 2-24 in the absence of disease progression or unacceptable toxicity. Patients also undergo mapping angiography during screening, as well as CT and MRI or PET/CT during screening and on study. Patients also undergo blood sample collection throughout the trial and may undergo tumor biopsy during screening and on study.
Group II: Cohort I: (Y90, tremelimumab on day 1, cycle 1, durvalumab)Experimental Treatment9 Interventions
Patients receive transarterial Y90 radioembolization and tremelimumab IV over 1 hour on day 1 of cycle 1 and durvalumab IV over 1 hour on day 1 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo mapping angiography during screening as well as CT and MRI or PET/CT during screening and on study. Patients also undergo blood sample collection throughout the trial and may undergo tumor biopsy during screening and on study.
Durvalumab is already approved in European Union, United States, Japan for the following indications:
🇪🇺 Approved in European Union as Imfinzi for:
- Locally advanced, unresectable non-small cell lung cancer (NSCLC)
🇺🇸 Approved in United States as Imfinzi for:
- Extensive-stage small cell lung cancer (ES-SCLC)
- Limited-stage small cell lung cancer (LS-SCLC)
- Locally advanced or metastatic urothelial carcinoma
🇯🇵 Approved in Japan as Imfinzi for:
- Not specified in provided sources
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in FloridaJacksonville, FL
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
National Cancer Institute (NCI)Collaborator
References
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.
Tremelimumab: First Approval. [2023]Tremelimumab (tremelimumab-actl; IMJUDO®), a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blocking antibody, is being developed by AstraZeneca, under license from Pfizer, for the treatment of a range of malignant tumours. Tremelimumab was approved in the USA in October 2022 in combination with durvalumab for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). In addition, tremelimumab in combination with durvalumab and platinum-based chemotherapy was approved in the USA in November 2022 for the treatment of adult patients with metastatic non-small cell lung cancer (mNSCLC) with no sensitizing epidermal growth factor receptor mutation or anaplastic lymphoma kinase genomic tumour aberrations. In December 2022, tremelimumab in combination with durvalumab received a Positive Opinion from the EU Committee for Medicinal Products for Human Use for the first line treatment of adults with advanced or unresectable HCC. Tremelimumab in combination with durvalumab is under regulatory review for these indications in Japan and in other countries worldwide. This article summarizes the milestones in the development of tremelimumab leading to this first approval.
A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer. [2023]Tremelimumab (CP-675,206) is a fully human monoclonal antibody binding to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) on T cells that stimulates the immune system by blocking the CTLA4-negative regulatory signal. Combination with standard chemotherapy may strengthen antitumor therapy. This is a phase Ib, multisite, open-label, nonrandomized dose escalation trial evaluating the safety, tolerability, and maximum tolerated dose (MTD) of tremelimumab combined with gemcitabine in patients with metastatic pancreatic cancer.
FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma. [2023]On October 21, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma (uHC). The approval was based on the results from the HIMALAYA study, in which patients with uHC who were naïve to previous systemic treatment were randomized to receive one of three study arms: tremelimumab in combination with durvalumab (n=393), durvalumab (n=389), or sorafenib (n=389). The primary objective of improvement in overall survival (OS) for tremelimumab in combination with durvalumab compared to sorafenib met statistical significance with a stratified hazard ratio (HR) of 0.78 (95% confidence interval [CI], 0.66, 0.92; P=0.0035). The median OS was 16.4 months (95% CI, 14.2 to 19.6) with tremelimumab in combination with durvalumab and 13.8 months (95% CI, 12.3 to 16.1) with sorafenib. Adverse reactions occurring in ≥20% of patients receiving tremelimumab in combination with durvalumab were rash, fatigue, diarrhea, pruritus, musculoskeletal pain, and abdominal pain. The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg intravenous (IV) as a single dose in combination with durvalumab 1500 mg at Cycle 1/Day 1, followed by durvalumab 1500 mg IV every 4 weeks. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg IV as a single dose in combination with durvalumab 20 mg/kg IV, followed by durvalumab 20 mg/kg IV every 4 weeks.
Population pharmacokinetic modelling of tremelimumab in patients with advanced solid tumours and the impact of disease status on time-varying clearance. [2023]Tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 human monoclonal antibody of the immunoglobulin G2 κ isotype, has been studied in oncology clinical trials as both monotherapy and in combination with durvalumab. This study characterized the pharmacokinetics of tremelimumab as monotherapy and in combination with durvalumab and evaluated the impact of patient covariates on pharmacokinetics.
Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. [2023]Durvalumab is approved for the treatment of lung cancer, advanced biliary tract cancers, and is also being evaluated in many other solid organ tumors. The aim of our study is to define the incidence, etiology, and outcomes of liver injury in consecutive patients receiving durvalumab-based immunotherapy.
Durvalumab: First Global Approval. [2022]Intravenous durvalumab (Imfinzi™; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80), resulting in enhanced T-cell responses against cancer cells. The US FDA has granted durvalumab accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Durvalumab ± tremelimumab is under phase III clinical trials in urothelial carcinoma, non-small cell lung cancer, small cell lung cancer and head and neck squamous cell carcinoma. The drug is also being evaluated in phase I or II clinical trials in a wide range of solid tumours and haematological malignancies. This article summarizes the milestones in the development of durvalumab leading to this first approval for urothelial carcinoma.
Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. [2022]Efficacy of immune checkpoint inhibitors (ICI) as monotherapy in 2nd line treatment for gastric or gastro-oesophageal junction (GEJ) adenocarcinoma is low, with no evaluation of efficacy and safety of ICI combined with chemotherapy. The DURIGAST PRODIGE 59 study is a randomised, multicentre, phase II study designed to assess the efficacy and safety of the combination of FOLFIRI + Durvalumab +/- Tremelimumab as 2nd line treatment of patients with advanced gastric/GEJ adenocarcinoma. Here, we report data from the safety run-in phase with FOLFIRI Durvalumab (arm A) or FOLFIRI Durvalumab and Tremelimumab (arm B). Among the 11 patients included, 63.6% experienced at least one grade 3-4 adverse events (AEs) related to the treatment, most frequently neutropenia (36.4%). There was only one immune-related AE (grade 2 hyperthyroidism). Ten serious AEs were described among six patients, but only two were related to the treatment, due to the chemotherapy. One seizure epilepsy related to a brain metastasis was observed, but was not related by the investigator to the treatment. However, the Independent Data Monitoring Committee recommended brain imaging at inclusion. This safety run-in phase demonstrates an expected safety profile of FOLFIRI with Durvalumab +/- Tremelimumab combination allowing the randomised phase II.
Tolerability and efficacy of durvalumab, either as monotherapy or in combination with tremelimumab, in patients from Asia with advanced biliary tract, esophageal, or head-and-neck cancer. [2022]Agents targeting the programmed cell death-1 pathway have demonstrated encouraging activity across multiple solid tumor types. The dose expansion phase of this phase I study evaluated the safety, tolerability, and antitumor activity of durvalumab monotherapy, and durvalumab plus tremelimumab (an anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody) combination therapy, in patients from Asia with biliary tract cancer (BTC), esophageal squamous cell carcinoma (ESCC), or head and neck squamous cell carcinoma (HNSCC).
Tremelimumab (CP-675,206): a fully human anticytotoxic T lymphocyte-associated antigen 4 monoclonal antibody for treatment of patients with advanced cancers. [2021]Tremelimumab, a fully human monoclonal IgG2 antibody targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4), is being developed by Pfizer for treatment of patients with advanced cancers. Treatment with an anti-CTLA4 mAb prevents normal downregulation of T cells and prolongs T cell activation, thereby enhancing immune function. In Phase I and II studies, tremelimumab was well tolerated with predictable and manageable side effects. Antitumor activity with monotherapy was observed in patients with advanced melanoma and colorectal cancer (objective response rates of approximately 10 and 2%, respectively), and most objective responses were durable (defined as lasting > 180 days). Additional Phase II and III studies in combination with other agents will assess antitumor activity in multiple tumor types as well as attempt to identify patient populations most likely to respond.
Tremelimumab. [2023]Tremelimumab (CP 675206; CP-675; CP-675,206; CP-675206; Ticilimumab) is a fully human IgG2 anitbody, which is directed against human cytotoxic T lymphocyte-associated antigen 4 (CTLA4). It is being developed by Pfizer for the treatment of various cancers. It is currently in worldwide phase III development for malignant melanoma, phase II development for colorectal cancer, gastrointestinal cancer, gynecological cancer, and non-small cell lung cancer in the US and other countries, and is also being investigated for prostate, breast, and pancreatic cancer in various countries. This review discusses the key development milestones and therapeutic trials of this drug.