INDOCYANINE GREEN for Solid neoplasms of the digestive system|Colorectal cancer|Gastric cancer|Hepatobiliary cancer|Pancreatic cancer|Gastrointestinal neuroendocrine tumor

Inclusion criteria

• {"criterion_text":"- Be able to provide written informed consent for the study, particularly for the use of EVs loaded with ICG that are isolated from their own plasma through a plasmapheresis procedure with subsequent re-infusion of the galenic preparation OncoGreen.\n- Be aged 18 years or older at the time of signing the informed consent.\n- Have a histological or instrumental diagnosis of solid tumor of the digestive tract (primary and/or metastatic colon-rectal tumors, gastric tumors, tumors of the hepato-bilio-pancreatic and neuroendocrine districts) indicating the need for surgical resection under general anesthesia.\n- Have a performance status of 0-1 on the ECOG performance scale.\n- Meet technical and anesthesiologic eligibility for oncological surgical intervention for curative purposes. Specifically, routine hematological, hepatic, renal, and cardiorespiratory function tests compatible with extensive oncological surgery following good clinical practice.\n- Be eligible for preoperative plasmapheresis procedure as evaluated by a specialist in transfusion medicine (including clinical reassessment, complete blood count, comprehensive biochemistry with electrolytes (Ca/Na/K), complete coagulation profile, and recent ECG.\n- Have no active infection for HIV, HCV, HBV and Syphilis at enrollment proved by negativity of PCR for viral infection or negativity of a second level test for Syphilis in case of positive serology."}

Exclusion criteria

• {"criterion_text":"- History of allergies or reactions to contrast agents or ICG.\n- Chronic therapies or general, metabolic, or hematological conditions that contraindicate surgery or plasma collection through plasmapheresis.\n- Psychiatric disorders or substance abuse that would interfere with the necessary cooperation for the study.\n- Pregnancy or breastfeeding or planning to conceive from the clinical evaluation for enrollment up to 120 days after the surgical intervention, a period further extendable based on specific oncological indications for the individual case, for example, the need for adjuvant therapy.\n- During Phase II, patients who undergo plasmapheresis and EVs injection but, for whatever reason unrelated to the study, are not able to undergo surgery or receive intraoperative visualization, will be excluded from the study.\n- Ongoing therapies with drugs significantly interfering with hepatic function and ICG clearance (alloperidol, nitrofurantoine, phenobarbital, atropine, scopolamine, primidone)."}

Primary endpoints

• {"endpoint_text":"- Phase I: Evaluation of overall safety profile characterized by occurrence of DLTs, type, severity and duration of the adverse events. Phase II: Presence of tumor at histological examination in all surgical specimens that are visualized with OncoGreen in vivo and absence in non-visualized lesions: the procedure will be deemed effective if the tumor tissue is present in at least 75% of visualized lesions and absent in 75% of non-visualized lesions; otherwise, it will be considered ineffective.","definition_or_measurement_approach":"Phase I: Safety and tolerability characterized by occurrence of dose-limiting toxicities (DLTs), and by type, severity and duration of adverse events. Phase II: Effectiveness defined by histological confirmation: procedure deemed effective if tumor tissue is present in ≥75% of visualized lesions and absent in ≥75% of non-visualized lesions (histological examination of surgical specimens)."}

Secondary endpoints

• {"endpoint_text":"- Phase I - Pharmacokinetic parameters (maximum concentration [Cmax], area under the curve [AUC], and half-life [t1/2]) of ICG in the presence of EVs.","definition_or_measurement_approach":"Measurement of ICG PK parameters: Cmax, AUC, t1/2 in presence of EVs (pharmacokinetic sampling and analysis)."}
• {"endpoint_text":"- Phase II - 1.Intraoperative imaging success rate (iSR): success in obtaining intraoperative visualization of the tumor tissue.","definition_or_measurement_approach":"Intraoperative imaging success rate: binary assessment of successful intraoperative visualization of tumor tissue."}
• {"endpoint_text":"- Phase II - 2.Percentage of success in obtaining adequate post-operative imaging (post-operative imaging success rate, pSR).","definition_or_measurement_approach":"Post-operative imaging success rate: percentage of cases with adequate post-operative imaging."}
• {"endpoint_text":"- Phase II - 3.Percentage of success in obtaining adequate microscopic imaging (microscopic imaging success rate, mSR).","definition_or_measurement_approach":"Microscopic imaging success rate: percentage of cases with adequate microscopic imaging."}
• {"endpoint_text":"- Phase II - 4.In vivo and ex vivo intensity of tumor fluorescence.","definition_or_measurement_approach":"Measurement of fluorescence intensity in vivo and ex vivo (quantitative fluorescence measurement)."}
• {"endpoint_text":"- Phase II - 5.Imaging sensitivity.","definition_or_measurement_approach":"Imaging sensitivity: sensitivity of the imaging technique (comparison to reference methods; calculation of sensitivity)."}
• {"endpoint_text":"- Phase II - 6.Imaging specificity.","definition_or_measurement_approach":"Imaging specificity: specificity of the imaging technique (comparison to reference methods; calculation of specificity)."}
• {"endpoint_text":"- Phase II - 7.TBR: tumor-to-background ratio.","definition_or_measurement_approach":"Tumor-to-background ratio (TBR): quantitative ratio of tumor fluorescence signal to background signal."}
• {"endpoint_text":"- Phase II - 8.ICG delivery rate to the tumor tissue.","definition_or_measurement_approach":"ICG delivery rate: measurement/estimation of how effectively ICG is delivered to tumor tissue (quantitative assessment)."}
• {"endpoint_text":"- Phase II - 9.Percentage of cases where new (previously undetected) disease locations are identified.","definition_or_measurement_approach":"Percentage of cases with newly identified disease locations compared to prior imaging (detection rate of previously undetected lesions)."}
• {"endpoint_text":"- Phase II - 10.Percentage of patients with treatment emergent adverse events as defined by CTCAE v.5.0.","definition_or_measurement_approach":"Percentage of patients experiencing treatment-emergent adverse events graded per CTCAE v5.0."}
• {"endpoint_text":"- Phase II - 11.Maximum grade of each adverse event as defined by CTCAE v.5.0.","definition_or_measurement_approach":"Maximum grade per adverse event rated according to CTCAE v5.0."}
• {"endpoint_text":"- Phase II - 12.Local recurrence-free survival (LocRFS).","definition_or_measurement_approach":"Local recurrence-free survival (LocRFS): time-to-event measure for local recurrence-free survival."}

Italy

Earliest CTIS Part Ii Submission Date

30-05-2025

Latest Decision Or Authorization Date

08-10-2025

Processing Time Days

131

Number Of Sites

1

Number Of Participants

44

Primary sponsor

Full Name

Universita Degli Studi Di Milano

Organisation Type

Educational Institution

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Clinical Research Technology S.r.l.","duties_or_roles":"Sponsor duties codes: 1,10,5,6,7,8","organisation_type":"Pharmaceutical company"}