Nano-Carbon Iron Suspension Injection Combined With Radiotherapy for Solid Tumors Phase II Clinical Trial

A Multicenter, Open-label Phase II Clinical Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Intratumoral Injection of Carbon Nanoparticle Iron Suspension (CNSI-Fe) in Combination With Radiotherapy in Patients With Solid Tumors

Study Primary Objective: To evaluate the efficacy of CNSI-Fe intra-tumoral injection combined with radiotherapy in patients with solid tumors.

Study Secondary Objectives:

1. To evaluate the efficacy of CNSI-Fe intra-tumoral injection combined with radiotherapy at both injected and non-injected lesions;
2. To evaluate the safety and tolerability of CNSI-Fe intra-tumoral injection combined with radiotherapy in patients with solid tumors;
3. To evaluate the pharmacokinetic (PK) characteristics of CNSI-Fe intra-tumoral injection combined with radiotherapy in patients with solid tumors.

Study Population: Patients with histologically or cytologically confirmed solid tumors including soft tissue sarcoma, head and neck squamous cell carcinoma, etc., who are assessed by the investigator as suitable for standard radiotherapy including preoperative neoadjuvant radiotherapy (Cohort A1) or definitive radiotherapy for patients not suitable for surgery (Cohort A2)

Study Drug Administration Schedule: Single administration, 2 weeks per administration cycle, total 1-4 cycles

Study Primary Endpoint: Objective Response Rate (ORR) assessed according to RECIST 1.1 criteria

Study Key Secondary Endpoints:

1. Patients with unresectable locally advanced or advanced solid tumors: Local Control Rate (LCR), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR), Time to Progression (TTP), Time to Response (TTR), and Overall Survival (OS);
2. Patients receiving preoperative neoadjuvant therapy: Major Pathological Response (MPR), Disease-Free Survival (DFS), Disease Control Rate (DCR);

Inclusion Criteria:

1. Participants voluntarily sign a written Informed Consent Form (ICF), can communicate effectively with the investigator, and are able to comply with study requirements.

2. Age ≥ 18 years and ≤ 80 years, regardless of gender.

3. Histologically or cytologically confirmed solid tumors, including soft tissue sarcoma, head and neck squamous cell carcinoma, etc., assessed by the investigator as suitable for standard radiotherapy, including preoperative neoadjuvant radiotherapy (Cohort A1) or definitive radiotherapy for patients unsuitable for surgery (Cohort A2).

4. ECOG score of 0-1.

5. Estimated survival ≥ 12 weeks.

6. Limited oligometastasis (≤ 5 lesions).

7. According to RECIST 1.1 criteria, participants have at least one radiologically measurable lesion that has not previously received radiotherapy (unless the lesion progressed clearly after radiotherapy).

8. At least one injectable lesion (e.g., directly injectable or via medical imaging guidance), determined by the investigator to be suitable for repeated intratumoral injection.

9. Drug-related adverse reactions from prior treatments have recovered to Grade 1 or lower per NCI CTCAE v6.0 at screening (excluding alopecia, Grade 2 or lower peripheral neurotoxicity, or other toxicities judged by the investigator to pose low safety risk).

10. Left ventricular ejection fraction (LVEF) ≥ 50% assessed by cardiac evaluation.

11. Within 7 days prior to first dosing, adequate hematologic and end organ function per laboratory tests meeting the following criteria:

    1. Hematology No use of granulocyte colony-stimulating factor (G-CSF) or similar treatments within 14 days prior to hematology lab testing, and absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; No platelet transfusion or use of interleukin-11 (IL-11), recombinant human thrombopoietin injection, or similar treatments within 7 days prior to hematology lab testing, and platelet count (PLT) ≥ 90×10⁹/L; No blood transfusion or use of erythropoietin within 14 days prior to hematology lab testing, and hemoglobin (Hb) ≥ 90 g/L;
    2. Coagulation function International normalized ratio (INR) ≤ 1.5×upper limit of normal (ULN), activated partial thromboplastin time (APTT) ≤ 1.5×ULN; Note: Participants receiving anticoagulant therapy with injectable lesions in the skin and/or subcutaneous tissue may have prolonged INR and APTT as direct pressure can control excessive bleeding, determined by the investigator; for participants receiving anticoagulant therapy and undergoing deep lesion injection, discontinuation of anticoagulant therapy for at least 1 week prior to injection is recommended, determined by the investigator.
    3. Renal function Serum creatinine (Cr) ≤ 1.5×ULN, or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula (creatinine clearance calculation is performed only when baseline Cr > 1.5×ULN);
    4. Hepatic function total bilirubin (TBIL) ≤ 1.5×ULN, or ≤ 3×ULN for participants with Gilbert's syndrome or hepatic metastases; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations ≤ 3×ULN, or ≤ 5×ULN if elevated due to hepatic metastases as determined by the investigator; Serum albumin ≥ 2.8 g/dL.

12. Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dosing of study drug, commit to practicing effective contraception or abstinence during the study drug treatment period and for 6 months after completion of study drug treatment, and must not be lactating.

Male participants must commit to practicing effective contraception or abstinence during the study drug treatment period and for 6 months after completion of study drug treatment. Additionally, male participants must agree not to donate sperm during this period.

Exclusion Criteria:

1. History or current diagnosis of iron metabolism disorders (excluding participants with iron deficiency anemia), such as thalassemia, favism (red blood cell glucose-6-phosphate dehydrogenase deficiency), etc.
2. Evidence of hollow viscus perforation at the injection site either previously or currently.
3. Local skin ulceration, erythema, necrosis, hemorrhage or other conditions affecting investigational drug administration at the injection site either previously or currently.
4. Known history or current coagulation defects causing increased bleeding risk, or any known hemorrhagic disorders.
5. Received systemic chemotherapy, small molecule targeted therapy or hormonal anti-tumor treatment within 2 weeks prior to first administration of investigational medication; received macromolecular biologics anti-tumor treatment within 4 weeks prior to first administration of investigational medication; received prior radiotherapy within 14 days prior to first administration of investigational medication [central nervous system (CNS) radiotherapy excluded, requiring ≥28 days washout period]; received traditional Chinese medicine with anti-tumor indication within 14 days prior to first administration of investigational medication.
6. Undergone major surgical procedures (craniotomy, thoracotomy or laparotomy) within 4 weeks prior to first administration of investigational medication, or other surgical conditions deemed unsuitable for enrollment by the investigator (fine needle aspiration at tumor site is allowed).
7. Contraindications for concomitant therapy: infection, active inflammation, severe skin lesions or other conditions deemed unsuitable for radiotherapy at the intended irradiation sites;
8. Untreated or active brain metastases, spinal cord compression, carcinomatous meningitis, or other evidence indicating uncontrolled central nervous system metastases (excluding cases with stable symptoms after treatment, radiological evidence of stability for at least 4 weeks prior to first administration, absence of cerebral edema evidence, and no requirement for corticosteroid treatment).
9. Uncontrolled or poorly controlled hypertension (e.g., systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg).
10. Uncontrolled tumor-related pain.
11. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once/month or more frequently).
12. Received live virus vaccination within 4 weeks prior to first administration of investigational medication.
13. History of immunodeficiency disease, including human immunodeficiency virus (HIV) positive status or other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
14. Active hepatitis B virus (HBV) infection [HBV DNA quantitative >500 IU/mL], or hepatitis C virus (HCV) infection [HCV antibody positive with HCV ribonucleic acid (RNA) polymerase chain reaction (PCR) exceeding upper limit of normal].
15. Severe chronic or active infection (including tuberculosis infection) requiring systemic antibacterial, antifungal or antiviral treatment prior to first administration of investigational medication, viral hepatitis participants receiving antiviral treatment are allowed.
16. Other active malignancies outside the study tumor type occurred within 5 years prior to first administration of investigational medication, excluding non-melanoma skin cancers treated with curative intent, localized prostate cancer, ductal carcinoma in situ, stage I endometrial cancer, cervical carcinoma in situ, differentiated thyroid cancer or breast carcinoma in situ.
17. History of severe heart failure, stroke or transient ischemic attack within 6 months prior to first administration of investigational medication. History of ventricular tachycardia or torsade de pointes arrhythmia within 14 days prior to first administration, and any clinically significant abnormalities in rhythm, conduction or morphology on resting ECG. Diagnosed with clinically significant cardiac diseases including acute myocardial infarction, III or IV class congestive heart failure (New York Heart Association classification, see Appendix 3), unstable angina pectoris or arrhythmias requiring treatment within 6 months prior to first administration. Note: Participants with arrhythmia receiving anti-arrhythmic medication with controlled heart rate rhythm as shown on screening ECG may be enrolled.
18. Participated in other interventional clinical studies within 3 weeks prior to first administration of investigational medication (calculated from the day after last administration in previous study, excluding cases without exposure to investigational drugs or medical devices).
19. Diagnosed with active psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, etc.).
20. Participants with known allergy or intolerance to active ingredients or excipients in the investigational medication.
21. Other conditions deemed unsuitable for enrollment by the investigator.