Ignite Creation Date:
2024-05-06 @ 8:25 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06375915
Status:
RECRUITING
Last Update Posted:
2024-05-24
First Post:
2024-03-04
Brief Title:
Precision Medicine in Patients With Unresectable CholAngiocarcinoma RadioEmbolization and Combined Biological Therapy
Sponsor:
Francesco De Cobelli
Organization:
IRCCS San Raffaele
Study Overview
Official Title:
Single Arm Multicenter Phase II Study Investigating the Efficacy and Safety of a Novel Therapeutic Scheme in Patients With Unresectable CholAngiocarcinoma RadioEmbolization in Combination With CisGem and Durvalumab MEDI4736
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PM-CARE
Brief Summary:
Underlying disease mechanisms are fundamental for correct treatment selection and patient management in highly invasive and debilitating non-transmissible diseases Even though overall disease burden of cancer may have decreased due to a higher degree of awareness the availability of high-quality healthcare and early diagnosis may become challenging in certain neoplasms Cholangiocarcinoma is usually diagnosed at advanced stages due to non-specific presentation and is frequently refractory to chemotherapy causing a massive impact on patients and their families Surgery is currently the only curative treatment but is available to only approximately 30 of patients The combination of interventional- and immune-oncology to standard of care creates the perfect substrate for synergistic mechanisms to fight tumor growth in situ cell death following transarterial embolizationTARE elicits immune mediated response inflammatory response and biomarkers of oxidative stress and increases antigen presenting T-cells which an anti-anti progam death ligand PD-L1 can bind to standard of care can then add on with its known effectsThe rationale of a combined- locoregional and systemic - treatment lies in the synergistic effects of each of the treatments
Detailed Description:
Tumors are highly selective and well defined abnormal cellular proliferations in which microenvironment plays an important role in response to treatment Intrahepatic Cholangiocarcinoma iCCA a tumor derived from the epithelia cells of the bile duct is particularly invasive and malignant Personalized treatment options with documented efficacy in patients with iCCA are still not available due to the complex and heterogenous molecular pathogenesis which has not been holistically described Disease models have limited reproducibility underlying chronic cholestatic disease chronic inflammation and risk factors contribute to the complexity and diversity of tumor microenvironment Although novel systemic therapeutic agents show improvement compared to standard of care chemotherapy a significant percentage of patients still does not respond to treatment maybe due to molecularimmunologic features which confer resistance Local treatment prior to systemic therapy has shown to induce subtle changes in the tumor microenvironment and a systemic immune response engagement of the immune system may therefore lead to enhanced and long term immunosurveillance and therefore lasting benefits for cancer patients
Combined systemic treatment with an anti PD-L1 that binds to the programmed cell death protein 1 and the standard of care SOC protein kinase inhibitor sorafenib and gemcitabine which inhibits DNA synthesis have been used in clinical trials for other primary liver indications and in patients with biliary tract cancers TOPAZ trial
Radioembolization TARE combines the embolization properties of microspheres with the radiant effect of Yttrium-90 Y-90 The locally treated tumor tissue is left in place and releases tumor-associated antigens and danger-associated molecular peptides originating from dead or dying cancer cells which promote the activation of antigen presenting cells and anti-tumor CD8T cells The resulting development of a systemic immune response following local treatment may lead to tumor regression at different sites than the one treated locally leading to the so-called abscopal effect
Comprehensive evaluations in patients undergoing combined treatment may allow a better understanding of tumor pathophysiology as well as the optimization of combined treatment schemes
This study will investigate the efficacy primary endpoint overall response rate according to mRECIST modified Response Evaluation Criteria in Solid Tumors and safety of the association of locoregional radioembolization followed by the combination of standard of care SOC chemotherapy with Cisplatin and Gemcitabine and durvalumab in patients with liver predominant unresectable intrahepatic cholangiocarcinoma The biological profile of patients prior to and following locoregional treatment and the effect of systemic therapy will be characterized in terms of potential biomarkers such as quantitative non-invasive radiological based parameters tumor tissue profiling and evaluation of biological substrates to help define and stratify patients with higher response and better outcome
Combined systemic treatment with an anti PD-L1 that binds to the programmed cell death protein 1 and the standard of care SOC protein kinase inhibitor sorafenib and gemcitabine which inhibits DNA synthesis have been used in clinical trials for other primary liver indications and in patients with biliary tract cancers TOPAZ trial
Radioembolization TARE combines the embolization properties of microspheres with the radiant effect of Yttrium-90 Y-90 The locally treated tumor tissue is left in place and releases tumor-associated antigens and danger-associated molecular peptides originating from dead or dying cancer cells which promote the activation of antigen presenting cells and anti-tumor CD8T cells The resulting development of a systemic immune response following local treatment may lead to tumor regression at different sites than the one treated locally leading to the so-called abscopal effect
Comprehensive evaluations in patients undergoing combined treatment may allow a better understanding of tumor pathophysiology as well as the optimization of combined treatment schemes
This study will investigate the efficacy primary endpoint overall response rate according to mRECIST modified Response Evaluation Criteria in Solid Tumors and safety of the association of locoregional radioembolization followed by the combination of standard of care SOC chemotherapy with Cisplatin and Gemcitabine and durvalumab in patients with liver predominant unresectable intrahepatic cholangiocarcinoma The biological profile of patients prior to and following locoregional treatment and the effect of systemic therapy will be characterized in terms of potential biomarkers such as quantitative non-invasive radiological based parameters tumor tissue profiling and evaluation of biological substrates to help define and stratify patients with higher response and better outcome
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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 |
|---|---|---|---|
| PNRR-MAD-2022-12375905 | OTHER_GRANT | Italian Ministry of Health | None |