Ignite Creation Date:
2024-05-06 @ 7:34 PM
Last Modification Date:
2024-10-26 @ 3:09 PM
Study NCT ID:
NCT06058663
Status:
RECRUITING
Last Update Posted:
2024-06-11
First Post:
2023-09-06
Brief Title:
Radioembolization With Tremelimumab and Durvalumab for Locally Advanced Unresectable or Oligo-Metastatic Intrahepatic Cholangiocarcinoma
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
Phase 1 Trial of Safety and Preliminary Efficacy of Segmental Ablative Radioembolization in Combination With Tremelimumab Plus Durvalumab MEDI4736 in Patients With Unresectable or Oligo-Metastatic Cholangiocarcinoma Who Are Not Candidates for Curative Therapy RAIDEN Trial
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 bodys 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
Detailed Description:
PRIMARY OBJECTIVE
I Characterize the safety of the combination of Y90 transarterial radioembolization TARE durvalumab and tremelimumab
SECONDARY OBJECTIVES
I Overall efficacy of Y90 tremelimumab durvalumab as gauged by response rate Response Evaluation Criteria in Solid Tumors RECIST version v11 modified mRECIST and Positron Emission Tomography PET PERCIST
II Median progression free survival PFS and overall survival OS III Infield and out of field objective response rate complete response and partial response rate RECIST v11 mRECIST and PERCIST In-field and out of- field duration of response
IV Correlatives
IVa Studies pertaining to serial circulating tumor deoxyribonucleic acid ctDNA - liquid biopsies testing as well as immune-panel based profiling will be performed alongside pre- and post-biopsies to study changes in the tumor microenvironment IVb Post-treatment dose volume histograms will be obtained using Simplicity software IVi Tissue immunohistochemistry and Tissue Digital Spatial Profiling - list of biomarkers CD68 CD 86 CD163 CSF1R - macrophage M1M2 markers CD3 - T-cell differentiator FoxP3 CD25 CD4 and 8 - T-cell lineage PD-1 PD-L1 etc - checkpoints granzyme B - cytotoxic T lymphocytes CTL activity Next generation Gen profiling and ribonucleic acid RNA sequencing Microsatellite instability MSI mismatch repair MMR status tumor mutational burden TMB IVii Peripheral blood white blood cell count WBC absolute neutrophil count ANC absolute lymphocyte count ALC absolute monocyte count AMC ANC to ALC ANCALC ratio and myeloid to lymphoid lineage ML IViii Guardant 360 to assess ctDNA at baseline and evolution throughout treatment IViv Personalized ctDNA assay Signatera bespoke multiplex polymerase chain reaction mPCR next generation sequencing NGS assay by Natera specific to each patients tumor mutational signatures
EXPLORATORY OBJECTIVES
I Tissue and blood for predictive biomarkers
OUTLINE Patients are assigned to 1 of 2 arms
Arm I COHORT I Patients receive transarterial Y90 radioembolization and tremelimumab intravenously 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 computerized tomography CT and magnetic resonance imaging MRI or positron emission tomography PETCT during screening and on study Patients also undergo blood sample collection throughout the trial and may undergo tumor biopsy during screening and on study
Arm II COHORT II 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 PETCT during screening and on study Patients also undergo blood sample collection throughout the trial and may undergo tumor biopsy during screening and on study
Cohort III This is a dose expansion cohort where patients are enrolled based on the efficacy and safety results from Cohorts I and II
After completion of study treatment patients are followed up every 3 months for 2 years
I Characterize the safety of the combination of Y90 transarterial radioembolization TARE durvalumab and tremelimumab
SECONDARY OBJECTIVES
I Overall efficacy of Y90 tremelimumab durvalumab as gauged by response rate Response Evaluation Criteria in Solid Tumors RECIST version v11 modified mRECIST and Positron Emission Tomography PET PERCIST
II Median progression free survival PFS and overall survival OS III Infield and out of field objective response rate complete response and partial response rate RECIST v11 mRECIST and PERCIST In-field and out of- field duration of response
IV Correlatives
IVa Studies pertaining to serial circulating tumor deoxyribonucleic acid ctDNA - liquid biopsies testing as well as immune-panel based profiling will be performed alongside pre- and post-biopsies to study changes in the tumor microenvironment IVb Post-treatment dose volume histograms will be obtained using Simplicity software IVi Tissue immunohistochemistry and Tissue Digital Spatial Profiling - list of biomarkers CD68 CD 86 CD163 CSF1R - macrophage M1M2 markers CD3 - T-cell differentiator FoxP3 CD25 CD4 and 8 - T-cell lineage PD-1 PD-L1 etc - checkpoints granzyme B - cytotoxic T lymphocytes CTL activity Next generation Gen profiling and ribonucleic acid RNA sequencing Microsatellite instability MSI mismatch repair MMR status tumor mutational burden TMB IVii Peripheral blood white blood cell count WBC absolute neutrophil count ANC absolute lymphocyte count ALC absolute monocyte count AMC ANC to ALC ANCALC ratio and myeloid to lymphoid lineage ML IViii Guardant 360 to assess ctDNA at baseline and evolution throughout treatment IViv Personalized ctDNA assay Signatera bespoke multiplex polymerase chain reaction mPCR next generation sequencing NGS assay by Natera specific to each patients tumor mutational signatures
EXPLORATORY OBJECTIVES
I Tissue and blood for predictive biomarkers
OUTLINE Patients are assigned to 1 of 2 arms
Arm I COHORT I Patients receive transarterial Y90 radioembolization and tremelimumab intravenously 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 computerized tomography CT and magnetic resonance imaging MRI or positron emission tomography PETCT during screening and on study Patients also undergo blood sample collection throughout the trial and may undergo tumor biopsy during screening and on study
Arm II COHORT II 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 PETCT during screening and on study Patients also undergo blood sample collection throughout the trial and may undergo tumor biopsy during screening and on study
Cohort III This is a dose expansion cohort where patients are enrolled based on the efficacy and safety results from Cohorts I and II
After completion of study treatment patients are followed up every 3 months for 2 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MC1943 | OTHER | Mayo Clinic | None |
| NCI-2023-05200 | REGISTRY | None | None |
| 21-007474 | OTHER | None | None |