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

Sponsor

National Cancer Centre, Singapore (Other)

Overall Status

Completed

CT.gov ID

NCT04995185

Collaborator

Terry Fox Foundation (Other)

Enrollment

Locations

Arm

42.3

Actual Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Carcinoma	Radiation: (18)F-fluoromisonidazole (FMISO)	N/A

Detailed Description

The specific aims of this study are:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Jun 20, 2017

Actual Primary Completion Date :

Dec 30, 2020

Actual Study Completion Date :

Dec 30, 2020

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

To investigate the dynamics of tumour hypoxia [From baseline and during 7 week long treatment regimen]
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.
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. [At baseline and week 3 of RT]
Number of patients with feasible radiotherapy plan dose-escalation to more than 84Gy
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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