Assessing Tumor Response and IMRT Treat Plan After IC Based on FDG-PET/CT for Locally Advanced HNSCC

Phase 2

Completed

• Conditions: Head and Neck Squamous Cell Carcinoma
• Interventions: Radiation: IMRT; Radiation: PET/CT; Drug: Docetaxel; Drug: Fluorouracil; Drug: Cisplatin

• Registration Number: NCT02047201
• Lead Sponsor: Lithuanian University of Health Sciences

Brief Summary

To evaluate the safety and efficacy of cisplatin plus intensity-modulated radiotherapy (IMRT) based on FDG-PET/CT after induction chemotherapy (IC) for locally advanced head and neck squamous cell carcinoma.

Detailed Description

Current guidelines define that pre-IC target volumes must be used for radiotherapy (RT) planning. This prospective, phase II trial assessed the results of patients with locally advanced squamous cell carcinoma of head and neck treatment with IC following by chemoradiotherapy (CRT), using post-IC PET/CT images for IMRT planning.

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2014-01-22
• Study First Submitted QC: 2014-01-24
• Study First Posted: 2014-01-28
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-01
• Last Update Posted: 2016-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Male or female patients aged 18 years or over;
• Histologically confirmed locally advanced (stage III and IV) head and neck squamous cell carcinoma (HNSCC);
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
• Signed written informed consent approved by the Lithuanian Bioethics Committee (LBEC);

Exclusion Criteria

• Positive serum pregnancy test in women of childbearing potential or breastfeeding;

• Presence of distant metastasis;

• Second primary tumor;

• History of other malignancy within the last 5 years;

• Recurrent head and neck cancer;

• Serious uncontrolled concomitant disease that would contraindicate the use of any drugs use in this study as chemotherapy or radiotherapy; ;

• Inadequate organ function, evidenced by the following laboratory results:

  1. Absolute neutrophil count <1,500 cells/mm3;
  2. Platelet count <100,000 cells/mm3;
  3. Hemoglobin <9 g/dL;
  4. Total bilirubin greater than the upper limit of normal (ULN);
  5. AST (SGOT) or ALT (SGPT) >1,5 x ULN;
  6. Alkaline phosphatase levels >2,5 x the ULN;
  7. Serum creatinine >2,0 mg/dl or 177 umol/l.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	IMRT	Induction chemotherapy (Docetaxel, Cisplatin and Fluorouracil) following radiochemotherapy (IMRT using PET/CT images after IC for treatment planning + cisplatin iv 40 mg/m2 weekly).
Experimental	PET/CT	Induction chemotherapy (Docetaxel, Cisplatin and Fluorouracil) following radiochemotherapy (IMRT using PET/CT images after IC for treatment planning + cisplatin iv 40 mg/m2 weekly).
Experimental	Docetaxel	Induction chemotherapy (Docetaxel, Cisplatin and Fluorouracil) following radiochemotherapy (IMRT using PET/CT images after IC for treatment planning + cisplatin iv 40 mg/m2 weekly).
Experimental	Cisplatin	Induction chemotherapy (Docetaxel, Cisplatin and Fluorouracil) following radiochemotherapy (IMRT using PET/CT images after IC for treatment planning + cisplatin iv 40 mg/m2 weekly).
Experimental	Fluorouracil	Induction chemotherapy (Docetaxel, Cisplatin and Fluorouracil) following radiochemotherapy (IMRT using PET/CT images after IC for treatment planning + cisplatin iv 40 mg/m2 weekly).

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	24 months after treatment	PFS was defined as the time from the first day of IC first cycles to either progression or death.

Secondary Outcome Measures

Name	Time	Method
SUVmax reductions (%)	2 weeks after IC	The SUVmax was defined as (tissue activity) (mcCi/ml)/(injected dose) (mCI)/(patient weight) (kg) within the voxel having the highest activity within a given region of interest (ROI). The SUVmax predictive value for tumor response to IC was assessed by comparing reductions in SUVmax (SUVmax of second PET/CT difference from SUVmax of first PET/CT in percent) in IC responders versus non responders and correlation with PFS and OS.
Number (%) of participants with adverse events	12 and 24 months from chemoradiotherapy	Treatment acute toxicity during IC and CRT (chemoradiotherapy) was weekly assessed according to the National Cancer Institute Common Toxicity Criteria (NCI CTCAE) v.4.0. Late adverse events related with radiotherapy were assessed every three months after CRT using RTOG (Radiation Therapy Oncology Group) /EORTC (European Organization for Research and Treatment of Cancer) toxicity criteria.
Overall survival (OS)	24 months after treatment	OS was defined as the time from the first day of IC first cycles until death from any cause.
Tumour metabolic response (MTV) reduction (%)	2 weeks after IC	MTV was defined as the tumor volume with FDG uptake segmented by a gradient-based method and fixed threshold methods at \>40% of SUVmax. The MTV predictive value for tumor response to IC was assessed by comparing MTV's reduction (MTV of second PET/CT difference from MTV of first PET/CT in percent) in IC responders versus non responders and correlation with PFS and OS.
Total lesion glycolysis (TLG) reduction (%)	2 weeks after IC	The TLG was defined as (MTV) x (SUVmean). The TLG predictive value for tumor response to IC was assessed by comparing TLG reduction (TLG of second PET/CT difference from TLG of first PET/CT in percent) in IC responders versus non responders and correlation with PFS and OS.

Trial Locations

Locations (1)

Lithuanian University of Health Sciences; 🇱🇹 Kaunas, Lithuania