Carbon Nanoparticle-Loaded Iron [CNSI-Fe(II)] in the Treatment of Advanced Solid Tumor

NCT06048367 | Completed Phase 1 Results

• 1 other identifier: CNSI-Fe(II)
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I clinical trial aims to evaluate the safety, tolerability, pharmacokinetics (PK) profile and preliminary efficacy of intratumoral injection of Carbon Nanoparticle-Loaded Iron \[CNSI-Fe(II)\] in patients with advanced solid tumors. The study also aims to observe dose-limiting toxicities (DLT) of CNSI-Fe(II) to determine the maximum tolerated dose (MTD) or the highest injectable dose in humans, providing dosing guidelines for future clinical studies. CNSI-Fe(II) shows promise as an innovative tumor therapeutic agent due to its unique properties of ferroptosis. The study primarily focuses on assessing the potential efficacy of CNSI-Fe(II) in patients with advanced solid tumors, particularly in patients with Kras mutation, e.g., pancreatic cancer patients.

Conditions

Advanced Solid Tumor; Lung Cancer; Pancreas Cancer; Breast Cancer; Thyroid Cancer; Colorectal Cancer; Cervical Cancer; Ovarian Cancer; Vulva Cancer

Keywords

Intratumoral Injection; Carbon Nanoparticle-Loaded Iron; Advanced Solid Tumor; Ferroptosis; Dose Limited Toxicity; Maximum Tolerated Dose; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability Assessment of CNSI-Fe(II)

  This primary outcome measure is centered on the assessment of CNSI-Fe(II)'s safety and tolerability throughout the study. It encompasses the following assessments: Dose-Limiting Toxicity (DLT): This assessment involves the ongoing monitoring of adverse events, with a focus on determining their nature, severity, and frequency. Adverse events will be systematically categorized and reported according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Maximum Tolerated Dose (MTD): The MTD is a critical outcome measure representing the highest injectable dose in humans that can be safely administered without causing excessive adverse effects. The determination of MTD will be based on the careful observation and analysis of DLT data. The MTD was not determined in this Phase I study, and the MAD is 150mg. Units of Measure: DLT: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0. MTD: Milligrams (mg) of CNSI-Fe(II).

  21 days

Secondary Outcomes (38)

• PK Parameters Assessment: Cmax (ng/mL) Profile Assessment of CNSI-Fe(II) of First Dosage

  72 h

• PK Parameters Assessment: Tmax (h) Profile Assessment of CNSI-Fe(II) of First Dosage

  72 h

• PK Parameters Assessment: AUC (ng•h/mL) Profile Assessment of CNSI-Fe(II) of First Dosage

  72 h

• PK Parameters Assessment: t1/2 (h) Profile Assessment of CNSI-Fe(II) of First Dosage

  72 h

• Evaluated as CR (Complete Response) in the Preliminary Efficacy Assessment.

  Observation period for a single dose is 21~28 days, the observation period for two doses is doubled.

Study Arms (5)

CNSI-Fe(II) 30 mg

EXPERIMENTAL

30 mg CNSI-Fe(II) 30 mg: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Drug: CNSI-Fe(II) 30 mg

CNSI-Fe(II) 60 mg

EXPERIMENTAL

60 mg CNSI-Fe(II) 60 mg: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an dditional dose may be administered based aon the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Drug: CNSI-Fe(II) 60 mg

CNSI-Fe(II) 90 mg

EXPERIMENTAL

90 mg CNSI-Fe(II) 90 mg: The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Drug: CNSI-Fe(II) 90 mg

CNSI-Fe(II) 120 mg

EXPERIMENTAL

120 mg CNSI-Fe(II) 120 mg: The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Drug: CNSI-Fe(II) 120 mg

CNSI-Fe(II) 150 mg

EXPERIMENTAL

150 mg CNSI-Fe(II) 150 mg: The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Drug: CNSI-Fe(II) 150 mg

Interventions

CNSI-Fe(II) 30 mg DRUG

The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Also known as: Carbon Nanoparticle-Loaded Iron Intratumoral Injection

CNSI-Fe(II) 30 mg

CNSI-Fe(II) 60 mg DRUG

The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Also known as: Carbon Nanoparticle-Loaded Iron Intratumoral Injection

CNSI-Fe(II) 60 mg

CNSI-Fe(II) 90 mg DRUG

The trial comprises a treatment period, including the DLT evaluation period with a duration of 21 days, and a maintenance treatment period. If the subject completes DLT evaluation without intolerable toxicity, an additional dose may be administered based on the investigator's determination of the benefits outweighing the risks. The original protocol planned for three dose groups: 30 mg, 60 mg, and 90 mg. The protocol was amended on March 28, 2024, to add 120 mg and 150 mg dose groups. A single tumor lesion amenable to intratumoral injection will be selected, regardless of tumor size, number, or location. The drug should be administered at the dose specified for the current dose cohort. The injection volume should be adjusted based on the size of the injected lesion.

Also known as: Carbon Nanoparticle-Loaded Iron Intratumoral Injection

CNSI-Fe(II) 90 mg

CNSI-Fe(II) 120 mg DRUG

The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Also known as: Carbon Nanoparticle-Loaded Iron Intratumoral Injection

CNSI-Fe(II) 120 mg

CNSI-Fe(II) 150 mg DRUG

The dosing regimen is the same as that for the 30 mg, 60 mg, and 90 mg dose groups. Additionally, if a single lesion cannot accommodate the full corresponding dose of the investigational drug, additional lesions may be selected for simultaneous injection. When multiple lesions are injected, the drug distribution should be allocated proportionally according to the size of each lesion or determined based on the investigator's assessment of an appropriate distribution.

Also known as: Carbon Nanoparticle-Loaded Iron Intratumoral Injection

CNSI-Fe(II) 150 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria to be eligible:
• Understand and voluntarily sign the informed consent form (ICF), demonstrating willingness and ability to comply with all trial requirements.
• Male or female aged 18-80 years (inclusive) at the time of signing the ICF.
• Histologically or cytologically confirmed advanced solid tumors with ineffective current standard therapy (disease progression after treatment or intolerable treatment) or lack of effective standard treatment options. Eligible tumor types include colorectal cancer, pancreatic cancer, breast cancer, gastric cancer, cervical cancer, lung cancer, head and neck cancer, bile duct cancer, kidney cancer, prostate cancer, vulvar cancer, etc. Note: Patients with advanced solid tumors experiencing disease progression due to the inability to receive standard treatment for any reason or those with tumor types insensitive to existing standard treatments (e.g., pancreatic cancer, undifferentiated thyroid cancer, and sarcomas) after receiving first-line standard treatment are also eligible.
• Presence of at least one measurable lesion according to RECIST v1.1, which has not received radiation (except for lesions showing clear progression after radiation) or tissue biopsy within 7 days before the first dose.
• Lesions amenable to injection, either directly or with assistance from medical imaging.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 7 days before the first dose.
• Expected survival of ≥12 weeks.
• Adverse drug reactions (ADR) caused by previous treatments have recovered to Grade 1 or lower (except for alopecia) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 before screening.
• Left ventricular ejection fraction (LVEF) ≥50%.
• Within 7 days prior to the first dose, have adequate hematologic and end-organ function, with laboratory tests meeting the following criteria:
• Hematology No use of granulocyte colony-stimulating factor (G-CSF) within 14 days prior to hematology laboratory tests, and absolute neutrophil count (ANC) ≥1.5×109/L; No platelet transfusion within 14 days prior to hematology laboratory tests, and platelet count (PLT) ≥90×109/L; No blood transfusion or use of erythropoietin within 14 days prior to hematology laboratory tests, and hemoglobin (Hb) ≥90 g/L;
• Renal function Serum creatinine (Cr) ≤1.5×upper limit of normal (ULN) or calculated creatinine clearance (Ccr) ≥50 mL/min using the Cockcroft-Gault formula (only calculated if baseline Cr \>1.5×ULN);
• Hepatic function Total bilirubin (TBIL) ≤1.5×ULN (≤3.0×ULN for patients with Gilbert's syndrome or liver metastases);
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤3×ULN, patients with confirmed liver or bone metastases must meet the following criteria:

You may not qualify if:

• Patients meeting any of the following criteria cannot participate in this clinical study:
• History of iron metabolism disorders (except for patients with iron-deficiency anemia), such as thalassemia or glucose-6-phosphate dehydrogenase deficiency.
• History or current evidence of hollow organ perforation at the injection site.
• History or current skin breakdown, redness, swelling, necrosis, or bleeding at the injection site that may affect the administration of the investigational drug.
• Received radiotherapy or any antineoplastic therapy for the target lesion within 4 weeks before the first dose of the investigational drug or not reached 5 half-lives of the previous antineoplastic treatment \[including but not limited to chemotherapy, targeted therapy, immunotherapy, National Medical Products Administration (NMPA) approved antineoplastic traditional Chinese medicine, and other traditional Chinese medicines with antitumor effects\] before the first dose, whichever is shorter.
• Undergone major surgical intervention, significant trauma, or have wounds or ulcers that have not healed within 4 weeks before the first dose.
• Presence of life-threatening clinical manifestations of brain and central nervous system metastases at the time of enrollment.
• Poorly controlled hypertension (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
• Uncontrolled tumor-related pain.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once per month or more frequently).
• History of other malignancies within 5 years before the start of study treatment, except for non-melanoma skin cancer, localized prostate cancer, ductal carcinoma in situ, stage I uterine cancer, cervical intraepithelial neoplasia, or stage 0 breast cancer after curative treatment.
• Received live virus vaccines within 4 weeks before the start of study treatment. Note: Seasonal influenza vaccines administered by injection are usually inactivated, and their use is permitted. However, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• History of immunodeficiency diseases, including human immunodeficiency virus (HIV) positivity or acquired or congenital immunodeficiency diseases or organ transplantation.
• Active hepatitis B virus (HBV) infection \[positive for HBV surface antigen (HBsAg) or HBV core antibody (HBcAb) and HBV DNA quantification \>500 IU/mL\], hepatitis C virus (HCV) infection \[positive for HCV antibody and HCV ribonucleic acid (RNA) measured by polymerase chain reaction (PCR) above the upper limit of normal (ULN)\], or positive anti-human immunodeficiency virus antibody (Anti-HIV). Patients meeting any of these criteria are excluded.
• Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral treatment within 4 weeks before the start of study treatment, excluding diagnostic procedures.

Sponsors & Collaborators

• Sichuan Enray Pharmaceutical Sciences Company: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (7)

• Zanganeh S, Hutter G, Spitler R, Lenkov O, Mahmoudi M, Shaw A, Pajarinen JS, Nejadnik H, Goodman S, Moseley M, Coussens LM, Daldrup-Link HE. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat Nanotechnol. 2016 Nov;11(11):986-994. doi: 10.1038/nnano.2016.168. Epub 2016 Sep 26.

  PMID: 27668795 BACKGROUND

• Trujillo-Alonso V, Pratt EC, Zong H, Lara-Martinez A, Kaittanis C, Rabie MO, Longo V, Becker MW, Roboz GJ, Grimm J, Guzman ML. FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels. Nat Nanotechnol. 2019 Jun;14(6):616-622. doi: 10.1038/s41565-019-0406-1. Epub 2019 Mar 25.

  PMID: 30911166 BACKGROUND

• Xie P, Yang ST, Huang Y, Zeng C, Xin Q, Zeng G, Yang S, Xia P, Tang X, Tang K. Carbon Nanoparticles-Fe(II) Complex for Efficient Tumor Inhibition with Low Toxicity by Amplifying Oxidative Stress. ACS Appl Mater Interfaces. 2020 Jul 1;12(26):29094-29102. doi: 10.1021/acsami.0c07617. Epub 2020 Jun 22.

  PMID: 32510916 RESULT

• Xie P, Xin Q, Yang ST, He T, Huang Y, Zeng G, Ran M, Tang X. Skeleton labeled 13C-carbon nanoparticles for the imaging and quantification in tumor drainage lymph nodes. Int J Nanomedicine. 2017 Jul 11;12:4891-4899. doi: 10.2147/IJN.S134493. eCollection 2017.

  PMID: 28744123 RESULT

• Huang Y, Zeng G, Xin Q, Yang J, Zeng C, Tang K, Yang ST, Tang X. Carbon nanoparticles suspension injection for photothermal therapy of xenografted human thyroid carcinoma in vivo. MedComm (2020). 2020 Sep 10;1(2):202-210. doi: 10.1002/mco2.28. eCollection 2020 Sep.

  PMID: 34766118 RESULT

• Xie P, Yang ST, He T, Yang S, Tang XH. Bioaccumulation and Toxicity of Carbon Nanoparticles Suspension Injection in Intravenously Exposed Mice. Int J Mol Sci. 2017 Nov 29;18(12):2562. doi: 10.3390/ijms18122562.

  PMID: 29186019 RESULT

• Huang Y, Xie P, Yang ST, Zhang X, Zeng G, Xin Q, Tang XH. Carbon nanoparticles suspension injection for the delivery of doxorubicin: Comparable efficacy and reduced toxicity. Mater Sci Eng C Mater Biol Appl. 2018 Nov 1;92:416-423. doi: 10.1016/j.msec.2018.07.012. Epub 2018 Jul 4.

  PMID: 30184767 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Pancreatic Neoplasms; Breast Neoplasms; Thyroid Neoplasms; Colorectal Neoplasms; Uterine Cervical Neoplasms; Ovarian Neoplasms; Vulvar Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Head and Neck Neoplasms; Thyroid Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Vulvar Diseases

Results Point of Contact

• Title: Professor. Yongsheng Wang
• Organization: West China Hospital of Sichuan University

wangys@wchscu.cn

18980602258

Study Officials

• Yongsheng Wang, PhD & MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This Phase 1 clinical trial employs a dose escalation design for the investigation of Carbon Nanoparticle-Loaded Iron \[CNSI-Fe(II)\] in the treatment of advanced solid tumors. The study follows a "Sequential" Study Model and consists of unique arms for each dose level(30mg, 60mg, 90mg, 120 mg and 150 mg), using the traditional "3+3 method" for dose escalation.

Study Record Dates

• First Submitted: August 24, 2023
• First Posted: September 21, 2023
• Study Start: November 17, 2022
• Primary Completion: September 29, 2024
• Study Completion: February 6, 2025
• Last Updated: August 3, 2025
• Results First Posted: June 27, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)