Immunotherapy With Y90-RadioEmbolization for Metastatic Colorectal Cancer (iRE-C)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04108481|
Recruitment Status : Recruiting
First Posted : September 30, 2019
Last Update Posted : November 23, 2021
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer Metastatic Colon Cancer Metastatic Colorectal Cancer Rectal Cancer Liver Metastasis Colon Cancer Colo-rectal Cancer Colorectal Adenocarcinoma Colorectal Neoplasms Liver Metastases Colorectal Carcinoma||Drug: Durvalumab Radiation: Yttrium-90 RadioEmbolization||Phase 1 Phase 2|
The purpose of this clinical trial is to find out more about the side effects of immunotherapy with a form of radiation treatment for the cancer in the liver called Yttrium-90 RadioEmbolization (Y90-RE). An immunotherapy drug, durvalumab, will be given intravenously every 2 weeks. Investigators are studying what doses of durvalumab are safe for people in combination with this form of radiation treatment. Patients in this study will receive durvalumab, which is experimental and not approved by the U.S. Food and Drug Administration (FDA) for metastatic colorectal cancer. Microscopic radioactive particles (TheraSphere®) will be used for radioembolization to deliver the Y90 drug to the liver.
The number of doses of the immunotherapy drug (range: 2 to 5) will depend on the cohort patients are assigned to. There is no placebo. Everyone on the study is treated with immunotherapy alongside Y90-RadioEmbolization.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Accelerated titration design with an expansion phase once MTD is determined to treat up to a total of 18 patients.|
|Masking:||None (Open Label)|
|Official Title:||Immunotherapy Combined With Yttrium-90 RadioEmbolization in the Treatment of Colorectal Cancer With Liver Metastases [iRE-C - Clinical Trial]|
|Actual Study Start Date :||October 5, 2020|
|Estimated Primary Completion Date :||October 2022|
|Estimated Study Completion Date :||October 2022|
Experimental: Y90-RE in combination with immunotherapy (durvalumab)
The treatment phase starts of with the immunotherapy drug (durvalumab) - "priming doses" every 2 weeks prior to patient getting mapped and ready for treatment with Y90-RadioEmbolization.
Post-Y90-RE, treatment is approximately 2 months in combination with fixed doses (750 mg) of durvalumab. The number and timing of doses of durvalumab each patient will receive will depend on the dose level the patient is assigned to (range 2-5 doses of immunotherapy).
A single patient will be treated per dose level until the first dose limiting toxicity (DLT) is recorded. Once the first DLT is recorded, two additional patients are treated at the same dose level and the trial reverts to a standard 3+3 design. Up to 6 patients will be treated at each dose level. The maximum tolerated dose (MTD) will be defined as the highest dose level for which at most 1 out of 6 patients experience a DLT.
Radiation: Yttrium-90 RadioEmbolization
Microscopic radioactive particles (TheraSphere®) will be used for radioembolization to deliver the Y90 drug to the liver
- Determine the maximum tolerated dose (MTD) of Yttrium-90 radioembolization combined with immunotherapy durvalumab to treat liver-predominant metastatic colorectal cancer (mCRC) [ Time Frame: Initiation of treatment up to 8 weeks and 2 doses ("priming") of immunotherapy prior to Y90-RE. ]MTD will be defined as the highest dose level for which at most 1 out of 6 patients experience a dose-limiting toxicity (DLT) using CTCAE version 5.0.
- Incidence of adverse events (AE) per CTCAE version 5.0 [ Time Frame: Initiation of screening up to 2 years ]The number and severity of all adverse events (overall, by dose-level, and by tumor molecular subtype) will be tabulated and summarized.
- Determine overall response rate (ORR) [ Time Frame: Up to 2 months post treatment ]Overall response rate is defined as the proportion of evaluable patients that have achieved a complete response (CR) or partial response (PR) by RECIST v1.1 as well as mRECIST and iRECIST.
- Determine the disease control rate (DCR) [ Time Frame: Up to 2 months post treatment ]Disease control rate is defined as the proportion of evaluable patients that have achieved a complete response (CR), partial response (PR), or stable disease (SD) by RECIST v1.1 as well as mRECIST and iRECIST.
- Determine liver-specific progression free survival [ Time Frame: Up to 2 months post treatment ]Progression free survival is defined as the proportion of evaluable patients that have achieved liver-specific progression free survival (Liver-PFS)
- Determine overall progression free survival [ Time Frame: Up to 2 years ]Progression free survival is defined as the proportion of evaluable patients that have achieved overall progression free survival (PFS)
- Determine overall survival [ Time Frame: Up to 2 years ]Overall survival (OS) is defined as the time from randomization to death of any cause.
- Determine duration of response [ Time Frame: Up to 2 years ]Duration of response (DOR) is defined as the time measurement criteria for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented, taking as reference for PD the smallest measurements recorded since the treatment started.
- Circulating tumor DNA - ctDNA - liquid biopsy correlates [ Time Frame: Up to 2 months post treatment ]To determine changes in the expression profile and in levels of circulating tumor DNA (ctDNA) in blood pre- and post- treatment
- Immune correlates - tissue [ Time Frame: Up to 2 months post treatment ]To assess the changes in immune infiltration (TISSUE: tumor-infiltrating lymphocytes - TILs (CD-3, CD-8), PD-L1 and PD-1 expression, pre- and post-Y90-RE and immunotherapy)
- Immune correlates - blood [ Time Frame: Up to 2 months post treatment ]To analyze serial changes in immune cells (BLOOD) pre- and post-Y90-RE and immunotherapy
- Tumor tissue - correlates [ Time Frame: Up to 2 months post treatment ]To evaluate mutation burden by whole-exome sequencing pre- and post-treatment (TISSUE)
- Tumor tissue - correlates [ Time Frame: Up to 2 months post treatment ]To evaluate concomitant expression profile changes through RNA-Seq pre- and post-treatment (TISSUE)
- Abscopal effects [ Time Frame: Up to 2 months post treatment ]To report on any abscopal effects seen in terms of responses outside the Y90-RE field
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04108481
|Contact: Pashtoon Kasi, MD, MSfirstname.lastname@example.org|
|Contact: Mary Schall, BSNemail@example.com|
|Principal Investigator:||Pashtoon Kasi, MD, MS||University of Iowa|