18F-FMISO PET Guided Dose Escalation in Nasopharyngeal Carcinoma - a Feasibility and Planning Study

This study aims to investigate the use of 18F-FMISO PET in identifying hypoxic subvolume for dose escalation radiotherapy in nasopharyngeal cancer and thus improve local control without significant increase in toxicities.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: (18)F-fluoromisonidazole (FMISO)

Detailed Description

The specific aims of this study are:

1. To establish hypoxia imaging in NPC patients
2. Investigate the dynamics of tumor hypoxia before and during chemoradiation
3. Integrate hypoxia imaging into radiation treatment planning protocols
4. Design hypoxia adapted radiation schedules
5. Identify candidate hypoxia biomarkers

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
  • Singapore, Singapore, 169610
    • National Cancer Centre, Singapore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• T3-T4 disease with no evidence of distant metastasis.
• Histological diagnosis of WHO Type II or III NPC
• No evidence of distant metastases in staging work up (including lung, liver and bone imaging).
• Planned for upfront radiotherapy and/or chemotherapy.
• Cross sectional imaging of the primary and neck disease (MRI preferred)
• Performance status of ECOG grade 0 or 1
• No prior tumour therapy
• At least 21 years of age, of either sex.
• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential;
• Adequate bone marrow, renal and hepatic function defined as follows:

Bone marrow: WBC > 3000 / mm3 (ANC > 1500 / mm3 ) Platelets > 100 000 / mm3. Hb > 10 gm/dl Renal: serum creatinine within institutional normal range(or) lower than the lower limit of institutional normal range : calculated creatinine clearance > 50 ml / min Hepatic: enzymes (SAP, SGOT) < 2x normal: bilirubin < 24 mol / l.

Exclusion Criteria:

• Allergic to 18F-fluoromisonidazole or Nitroimidazoles
• Planned for neoadjuvant chemotherapy
• Uncontrolled hypercalcaemia: calcium 2.7 mmol/L (10.8 mg/dL).
• Other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).
• Have serious active infection.
• Pregnant or lactating female subjects and subjects with reproductive potential not implementing adequate contraceptive measures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• 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: PET/CT imaging; Intravenous injection of 370MBq ± 10% (18)F-fluoromisonidazole	Radiation: (18)F-fluoromisonidazole (FMISO); Patients do not need to be fasted prior to intravenous injection of 370MBq ± 10% (18)F-fluoromisonidazole. Scanning will be performed two hours after the injection. Patients will be scanned with their thermoplastic shell used in routine radiotherapy treatment for 10 minutes, followed by approximately 5 minutes scan of the upper chest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the dynamics of tumour hypoxia	A repeat 18F-FMISO-PET in week 3 of the 7 weeks long treatment regimen is planned. Fractionated radiotherapy is expected to induce reoxygenation within the tumor as iterative process by killing well oxygenated tumor cells with every fraction thereby reducing oxygen demand in the remaining tumor cells. Repetitive hypoxia imaging at week 3 allows for assessment of evolution of hypoxia during radiotherapy.	From baseline and during 7 week long treatment regimen
To evaluate proportion of patients with contour-able hypoxic volume as well as the feasibility of generating dose-escalation radiotherapy plan with dosimetrically achieved parameters for target volume and organs-at-risk.	Number of patients with feasible radiotherapy plan dose-escalation to more than 84Gy	At baseline and week 3 of RT
To estimate the correlation between immunohistochemical expression of CA-IX, VEGF and HIF-1a, (marker of hypoxia) and pre-treatment PET-SUV measurement		At baseline
To correlate 18F-FMISO PET uptake with tumor response at 3 months post radiotherapy, local control rate and disease free survival.		From baseline up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Centre, Singapore
• Collaborators: Terry Fox Foundation
• Investigators: Principal Investigator: Kiattisa Sommat, MD, National Cancer Centre, Singapore

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2017
• Primary Completion (Actual): December 30, 2020
• Study Completion (Actual): December 30, 2020

Study Registration Dates

• First Submitted: July 29, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: PET; Hypoxia; Nasopharyngeal cancer; FMISO
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: MISSION16

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