Monocentric, open-label, single-arm, phase I/II clinical trial to evaluate the use of the ONCOGREEN galenic formulation consisting of indocyanine green (ICG) with autologous extracellular vesicles (EVs) for in vivo diagnostics of solid neoplasms undergoing surgical removal - ONCOGREEN study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita Degli Studi Di Milano

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

10 Nov 2025 → ongoing

Decision date (initial)

2025-06-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Università degli Studi di Milano

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Diagnosis

Phase I
To evaluate safety and tolerability of OncoGreen and to determine the dose for the phase II (RP2D) of OncoGreen in patients with gastrointestinal tract tumors undergoing surgery with curative intent.

Phase II
Improvement of in-vivo visualization of neoplastic tissue and tumor margins during surgical oncology procedures through fluorescence imaging techniques emitted by the ICG molecule delivered to neoplastic tissue via autologous extracellular vesicles (EVs).

Secondary objectives 5

1. Phase I - To characterize the pharmacokinetic parameters of OncoGreen.
2. Phase II - 1.To calculate the sensitivity and specificity of the experimented technique compared to conventional pre-, intra-, and post-operative imaging methods.
3. Phase II - 2.To determine the efficiency of tumor-specific delivery using the studied technique.
4. Phase II - 3.To evaluate the safety and tolerability of OncoGreen in patients with gastrointestinal tract tumors undergoing surgery with curative intent.
5. Phase II - 4.Long-term evaluation of the efficacy of the experimental surgical technique with OncoGreen in high-risk recurrence patients.

Conditions and MedDRA coding

Solid neoplasms of the digestive system (primary and/or metastatic colon-rectal tumors, gastric tumors, tumors of the hepato-bilio-pancreatic and neuroendocrine districts) treatable with surgical resection for curative purposes

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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.
2. Be aged 18 years or older at the time of signing the informed consent.
3. 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.
4. Have a performance status of 0-1 on the ECOG performance scale.
5. 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.
6. 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.
7. 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 6

1. History of allergies or reactions to contrast agents or ICG.
2. Chronic therapies or general, metabolic, or hematological conditions that contraindicate surgery or plasma collection through plasmapheresis.
3. Psychiatric disorders or substance abuse that would interfere with the necessary cooperation for the study.
4. 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.
5. 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.
6. Ongoing therapies with drugs significantly interfering with hepatic function and ICG clearance (alloperidol, nitrofurantoine, phenobarbital, atropine, scopolamine, primidone).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 13

1. Phase I - Pharmacokinetic parameters (maximum concentration [Cmax], area under the curve [AUC], and half-life [t1/2]) of ICG in the presence of EVs.
2. Phase II - 1.Intraoperative imaging success rate (iSR): success in obtaining intraoperative visualization of the tumor tissue.
3. Phase II - 2.Percentage of success in obtaining adequate post-operative imaging (post-operative imaging success rate, pSR).
4. Phase II - 3.Percentage of success in obtaining adequate microscopic imaging (microscopic imaging success rate, mSR).
5. Phase II - 4.In vivo and ex vivo intensity of tumor fluorescence.
6. Phase II - 5.Imaging sensitivity.
7. Phase II - 6.Imaging specificity.
8. Phase II - 7.TBR: tumor-to-background ratio.
9. Phase II - 8.ICG delivery rate to the tumor tissue.
10. Phase II - 9.Percentage of cases where new (previously undetected) disease locations are identified.
11. Phase II - 10.Percentage of patients with treatment emergent adverse events as defined by CTCAE v.5.0.
12. Phase II - 11.Maximum grade of each adverse event as defined by CTCAE v.5.0.
13. Phase II - 12.Local recurrence-free survival (LocRFS).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita Degli Studi Di Milano

Sponsor organisation

Universita Degli Studi Di Milano

Address

Via Festa Del Perdono 7

City

Milan

Postcode

20122

Country

Italy

Scientific contact point

Organisation

Universita Degli Studi Di Milano

Contact name

Paolo Ciana

Public contact point

Organisation

Universita Degli Studi Di Milano

Contact name

Paolo Ciana

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications