Local Injection Methylene Blue Combined With Radiation in HNSCC Patients

A Phase I Pilot Study of Tumor Local Injection Methylene Blue Combined With Radiation for Radiation Resistance Local Recurrent Head and Neck Cancer Squamous Cell Carcinoma

The goal of this clinical trial is to investigate the effectiveness of Methylene Blue (MB) as a radiosensitizer in treating head and neck squamous cell carcinoma (HNSCC) that has recurred locally and is resistant to radiation therapy. It will also assess the safety of Methylene Blue. The main questions it aims to answer are:

Does Methylene Blue improve the outcomes for patients with recurrent HNSCC receiving radiation therapy? What side effects do participants experience while receiving Methylene Blue?

Participants will:

Receive weekly injections of Methylene Blue or placebo into the tumor over six weeks.

Undergo six weeks of concurrent radiation therapy. Be monitored regularly for treatment effects and document any side effects experienced during the trial.

This single-center clinical trial intends to recruit 10 eligible patients diagnosed with locoregional recurrence of HNSCC that is resistant to previous radiotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Cancer; Local Recurrent Tumor
• Intervention / Treatment: Drug: Methylene Blue (50 mg/10ml)

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taiwan
    • Taichung, Taiwan, Taiwan, 404
      • China Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. . Histologically confirmed squamous cell carcinoma of head and neck.
2. . Locoregional recurrence.
3. . After standard treatment of R/M HNSCC.
4. . Measurable disease. Defined as presence of at least one lesion as being ≥10 mm in at least one dimension measured with conventional computed tomography (CT) or ≥10 mm in at least one dimension measured with spiral CT scan or magnetic resonance imaging (MRI).
5. . Lesion selection criteria - at least 1 lesion to be injected must be measurable and greater than or equal to 1.5 cm and longest diameter not exceed 10 cm in principle.
6. . ECOG performance status ≤2.
7. . Age ≧20 years old; and life expectancy of at least 12 weeks.
8. . Prior treatments with radiation therapy for palliative management of non-target lesion metastatic disease is permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy, disease progression has been documented and all treatment related adverse events are ≦ grade 1 at the time of registration.
9. . Must not have received anticancer therapy used with an antineoplastic intent, including chemotherapy, immunotherapy, biologic, or any investigational therapy within 14 days prior to the first dose of study drug.
10. . No history of allergic reactions attributed to methylene blue.
11. . Patient consent must be obtained.
12. . Negative pregnancy test, Fertile patients must use effective contraception.

Exclusion Criteria:

1. . Presence of central nervous system (CNS) metastases.
2. . The organ function measured within 14 days prior to study entry as defined below: Absolute neutrophil count (ANC) less than 1,000/mm3, or platelets less than 100,000/mm3; serum bilirubin greater than 1.5 times the upper limit of normal range (ULN); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 times the ULN if no demonstrable liver metastases, or greater than 5 times the ULN in the presence of liver metastases; creatinine clearance ≤40 ml/min.
3. . Concomitant illness including uncontrolled infection or other active, uncontrolled disease such as congestive heart failure, angina pectoris, respiratory insufficiency, and arrhythmia.
4. . Documented hypersensitivity to methylene blue compound or compounds of similar chemical or biologic composition.
5. . Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylene blue intratumoral injection combined with radiation	Drug: Methylene Blue (50 mg/10ml); Methylene blue (50mg/10mL):Volume: 2 mL, 5 mL, 8 mL and 10mL are used for intratumoral injections in different lesion sizes.Frequency: weekly; Radiation dose: 50-60 Gy for target lesions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any unexpected severe adverse event resulting from the combination treatment.	The investigators specify that the key feasibility objectives for our study would be considered successful if the following are met: 80% of patients received methylene blue experience no unpredicted harm during the treatment of methylene blue. The definition of unpredicted harm includes death within one month after last dose of methylene blue administration, or unpredicted ≧ grade 3 AE during methylene blue administration. The severity of adverse events was assessed using CTCAE v5.0.	"through study completion, an average of 1 year"

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: China Medical University, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: November 22, 2025
• First Submitted That Met QC Criteria: February 21, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 21, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Phenothiazines; Methylene Blue
• Other Study ID Numbers: CMUH114-REC1-108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No