Low-cost Screening and Image-guided Photodynamic Therapy (PDT) of Premalignant and Malignant Oral Lesions

NCT ID: NCT06876038

Last Updated: 2025-03-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-31
• Study Completion Date: 2028-05-31

Brief Summary

The primary goal of this study is to see if photodynamic therapy (PDT) is effective for treatment of lesions in the oral cavity which have high risk of becoming oral cancer. PDT treatment uses a drug, called a photosensitizer, which makes the diseased cells become light-sensitive such that they are destroyed when laser light is delivered to the target lesion. In this study a new handheld device, called SITOS (a "Screen, Image and Treat Optical System), is used. The ability of this device to simultaneously visualize the inside of the mouth and deliver laser light to the target site will be evaluated. The main questions this study seeks to answer are:

• Can this treatment completely cure oral potentially malignant lesions (OPML) without need for surgery?
• Do lesions recur after PDT treatment?
• Is the SITOS device easy to use for the doctor and comfortable for the patient, both as an oral imaging device and as a treatment device?

Detailed Description

This study seeks to evaluate the efficacy of photodynamic therapy (PDT) using aminolevulinic acid (ALA) photosensitization for treatment of oral potentially malignant lesions (OPML) or early stage oral cancer. Eligible participants will have histopathologically confirmed high-grade dysplasia/HGD (severe/moderate dysplasia) or early stage cancer (carcinoma-in-situ, CIS) in the oral cavity. While PDT using ALA photosensitization has already been shown to be safe and effective for other indications it is not yet approved for use in treatment of oral lesions. Preliminary clinical studies have indicated that PDT is well tolerated and can achieve complete clearance of lesions with excellent healing of the oral mucosa. This study specifically seeks to evaluate the use of a new handheld optical device called the Screen, Image, and Treat Optical System (SITOS) which combines imaging and PDT light delivery. This device, which is similar in size and shape to a standard dental camera, contains integrated optics for imaging the characteristic fluorescence signal which results from ALA-induced protoporpohpryin IX photosensitization. This will be used for imaging-based guidance of light delivery for PDT, which uses a red diode laser that is also integrated into the device.

Potential study participants will be identified in screening sessions at the participating clinical sites or through referral. Those with potentially qualifying lesions and who consent to participate undergo will undergo pre-treatment investigation, including clinical information on the oral lesion, risk profile and baseline toxicity profile, and preliminary imaging.

For those who qualify for PDT treatment, photosensitization will use 5-ALA (20 mg/kg body weight 5-ALA-HCl, Gleolan) administered orally 2 to 4 hours before treatment. After administration of 5-ALA, exposure of eyes and skin to strong light sources (e.g., operating illumination, direct sunlight, or brightly focused indoor light) must be avoided for 24 hours. The lesion area to be treated will be anesthetized locally with 2% xylocaine with 1:100,000 adrenalin. If the patient or the investigator desires, he/she may undergo the procedure under general anesthesia or IV sedation. Following administration of 5-ALA, the participant will undergo image-guided SITOS-based PDT treatment. SITOS will be used in the imaging mode to establish background fluorescence before 5-ALA administration, and again after ALA photosensitization to provide visualization of the photosensitized lesion. For photoactivation, a total light dose of 100 J/cm^2 will require ~30 minutes, depending on the final irradiance generated by SITOS. This may be given in 10-minute fractions with brief breaks for comfort. At light delivery time, SITOS will be used for real-time visualization of light applicator positioning to ensure centering of the beam spot and margins around the lesion. The SITOS probe also has a snap-on collar to control spacing and beam spot size which is fixed in place. A bitewing is clipped on for stable positioning with a hygienic sleeve over the whole probe. SITOS will monitor photobleaching (the decrease in fluorescence due to photosensitizer degradation during PDT) in real time, switching to image mode with brief interruptions in light delivery (approximately ~ 1 sec). Once per minute, measurement of bleaching relative to pre-irradiation will be performed. Participants will be kept in a room without direct sunlight exposure. The patients will be discharged after 48 hours of monitoring and toxicity profile evaluation.

The lesion response will be evaluated three weeks after PDT treatment. If complete response is not observed PDT may be repeated for a maximum of three sessions total. The clinical responses will be defined as complete, partial, and not responding as per the modified RECIST criteria. The final response will be determined in three weeks after the last PDT treatment (maximum of three sessions). If the patients show complete clinical response in less than three sessions of PDT, the PDT will be stopped, and the patients will be followed up every 3 months for one year. Punch biopsy will be performed to confirm histologic response a minimum of three months after the last PDT administration. Any lesions showing histologic evidence of dysplasia are considered a persistent disease and recommended to undergo surgical excision.

Conditions

Oral Cancer; Oral Cavity Cancer; Oral Leukoplakia; Oral Lichen Planus; Oral Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

To evaluate the clinical efficacy of image guided photodynamic therapy to manage HGD-OPML

The participants will take 5-ALA in oral solution (20 mg/kg BW 5-ALA HCl) 2 to 4 hours prior to undergoing image guided SITOS based PDT treatment. PDT treatment will use a total light dose of 100 J/cm\^2 of 635 nm light (red light) delivered from a laser at an irradiance of approximately 50 mW/cm\^2 at the tissue surface. Participants will be admitted for 48 hours to monitor toxicity profile evaluation. The lesion response will be evaluated and the PDT treatment will be repeated, if required, once in every 3 weeks with a maximum of up to three sessions. The clinical responses will be evaluated during the clinical visits. If the patient shows complete clinical response in less than three sessions of PDT, the PDT will be stopped and the patients will be followed up every 3 months, for one year. If there is lack of complete response or relapse of the lesions during the follow up, the patients will be advised to undergo surgical excision.

Group Type: EXPERIMENTAL

5-Amino Levulinic Acid

Intervention Type: DRUG

5-ALA (Gleolan) orally (20 mg/kg BW 5-ALA HCl) 2 to 4 hours prior to undergoing image-guided SITOS-based PDT treatment

Interventions

5-Amino Levulinic Acid

5-ALA (Gleolan) orally (20 mg/kg BW 5-ALA HCl) 2 to 4 hours prior to undergoing image-guided SITOS-based PDT treatment

Intervention Type: DRUG

Other Intervention Names

Gleolan

Eligibility Criteria

Inclusion Criteria

1. One grossly visible OPML, with histopathologically confirmed diagnosis of moderate, severe, and carcinoma in situ measuring ≥ 10 mm in diameter.

2. Willing and available for follow-up for at least one year and at prerequisite time intervals.

3. All patients above the age of 18 years and willing to voluntarily give a signed informed consent.

4. Karnofsky Performance Score above 80 or ECOG 0 or 1.

5. The subjects meeting the following laboratory eligibility criteria during a time not older than 2 months before accrual

• Hemoglobin level above or equal to 10%
• WBC >3000/mm3
• Platelets count >100000/mm3
• Total bilirubin, AST (SGOT), ALT (SGPT) < 1.5 times the Upper Limit Normal
• eGFR > 60 ml/min
• Serum Creatine less than 2 times the Upper Limit of laboratory normal
• INR/ PT and PTT within laboratory normal limits

Exclusion Criteria

1. Hypersensitivity against active substances and porphyrins.

2. Known diagnosis of porphyria.

3. Simultaneous use of other potentially phototoxic substances (eg; tetracyclines, sulphonamides, fluoroquinolones, hypericin extracts).

4. Uncontrolled concurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled cardiac and renal diseases or psychiatric illness.

5. Subjects with inherited or acquired bleeding and clotting disorders

6. Women who are breastfeeding/ have a positive urine pregnancy test or are planning their family.

7. Patients who have taken supplements of retinol, beta carotene, vitamin E, Selenium, or other chemo-preventive therapy at least one month prior to the baseline visit.

8. Patients with histological evidence of no dysplasia, mild dysplasia, invasive carcinoma, and any active malignant disease.

9. Patients with behavioral and cognitive impairment.

10. Patients who are concurrently diagnosed and undergoing treatment for other head and neck cancers.

11. Patients with large lesions, which, in the investigator's opinion, may require reconstructive surgery after excision.

12. The subjects, in the opinion of the Institutional Principal Investigator, are not an appropriate candidate for study participation due to alcoholism and abstinence.

13. Patient who was in a clinical trial for 4 weeks before participation in the present trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

University of Arizona

OTHER

Sponsor Role: collaborator

Aligarh Muslim University

OTHER

Sponsor Role: collaborator

Karkinos Healthcare Hospitals Ernakulam, Kerala, India

UNKNOWN

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Massachusetts, Boston

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Celli

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tayyaba Hasan, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital, Boston, MA, United States

Jonathan Celli, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Massachusetts Boston, Boston, MA, United States

Moni A Kuriakose, MD

Role: PRINCIPAL_INVESTIGATOR

Karkinos Healthcare Hospitals Ernakulam, Kerala, India

Mohammad Akram, MD

Role: PRINCIPAL_INVESTIGATOR

Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Locations

Karkinos Healthcare Hospitals

Ernākulam, Kerala, India

Jawaharlal Nehru Medical College, AMU

Aligarh, Uttar Pradesh, India

Countries

India

Central Contacts

Jonathan Celli, PhD

Role: CONTACT

jonathan.celli@umb.edu

617-287-5715

Shakir Khan, PhD

Role: CONTACT

shakir.khan@umb.edu

781-350-0861

Facility Contacts

Bharat K Sarvepalli

Role: primary

bharatkumar.sarvepalli@karkinos.in

+91 8790469574

Mohammad Akram, MD

Role: primary

akramhayat@gmail.com

M A Bilal Hussain, MSc

Role: backup

bilaljnmc@gmail.com

+91 9997657256

References

Siddiqui SA, Siddiqui S, Hussain MAB, Khan S, Liu H, Akhtar K, Hasan SA, Ahmed I, Mallidi S, Khan AP, Cuckov F, Hopper C, Bown S, Celli JP, Hasan T. Clinical evaluation of a mobile, low-cost system for fluorescence guided photodynamic therapy of early oral cancer in India. Photodiagnosis Photodyn Ther. 2022 Jun;38:102843. doi: 10.1016/j.pdpdt.2022.102843. Epub 2022 Mar 31.

Reference Type: BACKGROUND

PMID: 35367616 (View on PubMed)

Other Identifiers

U01CA279862

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CA279862

Identifier Type: -

Identifier Source: org_study_id