Local Immunomodulation Combined With Radiofrequency Ablation for Unresectable Colorectal Liver Metastases (LICoRN-01)
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|ClinicalTrials.gov Identifier: NCT04062721|
Recruitment Status : Not yet recruiting
First Posted : August 20, 2019
Last Update Posted : August 20, 2019
The LICoRN-01 trial is a single-arm phase Ib/II study that will assess the efficacy and safety of radiofrequency ablation (RFA) plus in situ immunomodulation by hydrogel combining a TLR agonist and GM-CSF in patients with unresectable colorectal (CRC) liver metastases.
Primary objective: progression free survival (PFS) rate at 12 months (RECISTv1.1 criteria, thoraco-abdomino-pelvic CT-scan Q8W).
- to assess the safety profile;
- to assess the median PFS;
- to assess the response rate;
- to assess PFS and response according to iRECIST vs. RECIST v1.1 criteria;
- to assess overall survival (OS);
- to assess predictive markers of response (imaging, tumor, blood).
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Drug: Chemotherapy Procedure: Radiofrequency ablation (RFA) Drug: In situ immunotherapy||Phase 1 Phase 2|
Early clinical trials of immunotherapy in CRC have provided first evidence of activity of adoptive cell vaccines combining inactivated autologous tumor cells and BCG, a Toll Like Receptor (TLR) agonist. RFA induces tumor cell necrosis and apoptosis, leading to the activation of anti-tumoral immunity through the release, exposure or denaturation of tumor antigens, which are captured by dendritic cells. Associated pro-inflammatory effects increase the anti-tumoral immune response but remain insufficient to avoid recurrence. In a preclinical study in an aggressive rectal cancer model, complete and long-lasting tumor responses were achieved after RFA combined with in situ injection of an immunomodulatory hydrogel combining a TLR agonist and GM-CSF. These results were obtained without further adjuvant therapy after complete clearance of macroscopic liver lesions by RFA. BCG, Purified Protein Derivatives (PPD), Polysaccharide Typhoid (Typhim Vi®) can be used as TLR agonists. The hypothesis of the study is that local immunotherapy may reduce recurrence rates after RFA in patients with unresectable liver metastases from CRC.
Thermal ablation by RFA may be used as an inducer of anti-tumor immune response and the combination with immunomodulators such as a TLR agonist (BCG, PPD, Typhim Vi) and GM-CSF may improve its efficacy. In the recent preclinical study, the efficacy has been demonstrated on distant lesions (so called abscopal effect) of two immunomodulators combined in a muco-adherent hydrogel, injected in a RFA-treated tumor. The treatment was safe, without complication observed in the 50 treated mice. Complete macroscopic ablation by RFA combined with in situ immunomodulators may be able to prime an effective immune response capable of eradicating the microscopic residual disease.
The LICoRN-01 study aims to assess the safety and efficacy of the combination of RFA with in situ immunomodulation in patients with unresectable CRC liver metastases.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label Bi-centric Study of Local Immunomodulation Treatment Combined With Radiofrequency Ablation for Unresectable Colorectal Liver Metastases|
|Estimated Study Start Date :||September 2019|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2022|
Experimental: Chemotherapy + RFA + in situ immunotherapy
Chemotherapy + RFA + in situ immunotherapy in patients with non resectable CRC liver-only metastases.
Chemotherapy (at the investigator's choice) for ≥ 2 months before RFA (with controlled disease) and resumed 4-6 weeks after RFA to achieve 6-month total duration.
Procedure: Radiofrequency ablation (RFA)
Complete macroscopic ablation by RFA.
Drug: In situ immunotherapy
Hydrogel combining TLR agonist and GM-CSF will be injected in 2 distinct lesions after RFA.
- Progression free survivor (PFS) rate at 12 months [ Time Frame: at 12 months ]
Progression free survivor (PFS) rate at 12 months assessed by centralized review of computed tomography (CT)-scan imaging in evaluable patients. Evaluable patients to determine PFS at 12 months will be:
- Patients alive at 12 months and with a documented progression on CT-scan available at 12 months or before;
- Patients alive at 12 months and without a documented progression on CT-scan available at 12 months;
- Patients dead within 12 months.
- The PFS rate at 12 months will be defined as the proportion of patients who will be alive and without disease progression at 12 months after RFA, according to RECIST v1.1, assessed by centralized review of CT-scan imaging.
- Incidence of treatment-emergent adverse events [ Time Frame: at 30 days ]All grade and severe (grade 3-5) toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 including post-operative and immune-related complications within 30 days after surgery.
- Median PFS [ Time Frame: at 12 months ]Time from the date of RFA to progression according to RECIST v1.1, assessed by centralized review of CT-scan imaging, or death for any reason, whichever occurs first.
- Median overall survival (OS) [ Time Frame: at 24 month ]Time from the date of RFA to date of death.
- Response rate [ Time Frame: at 12 months and 24 months ]According to RECIST v1.1.
- Potential predictive biomarkers [ Time Frame: at baseline and every two months until 24 months ]Will be collected at baseline and every two months until 24 months after the day of RFA, biological data (blood and tumor tissue) for tumorous markers.
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): NCT04062721
|Contact: Robert Malafosse, MD||+ 33 1 49 09 47 email@example.com|
|Principal Investigator:||Robert Malafosse, MD||Digestive Surgery department, Ambroise Pare University Hospital, Boulogne-Billancourt, France|