squamous cell carcinoma of the head and neck
Conditions
Interventions
None listed
Sponsors
St. Luc University Hospital; Université Catholique de Louvain
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: •Patients randomized in any of the two arms of EORTC 1219 trial •No contraindication to FAZA-PET/CT: pregnant or breast-feeding woman; for woman subject of childbearing potential, a pregnancy test will be done within 72 hours before the examination. •Patients must be scanned on a PET/CT scanner accredited, and in compliance with the provided imaging guidelines. •Biopsy must be performed 2 weeks before imaging scans. •Patient must have given written informed consent to participate to the imaging sub-study. Additional eligibility criteria for the imaging sub-study •Delay between the baseline scan (FAZA-PET/CT) and the start of the radiotherapy = 18 years. * Tumor material available for central testing of the hypoxic gene signature * WHO performance 0-2. * All hematology and biochemical investigations, should be done within 4 weeks before randomization (maximum 6 weeks before treatment starts) * Normal bone marrow function based on routine blood samples, i.e. neutrophils >= 1.0 x 109/L, platelets >= 75 x 109/L, hemoglobin >= 10.0 g/dL or 6.2 mmol/L * Normal kidney function creatinine clearance >= 60 mL/min, and Electrolyte balance: calcium = 1.2 mg/dl or 0.5 mmol/L * Normal liver function assessed by routine laboratory examinations, i.e. bilirubin < 1.5 x ULN, ALT< 3 x ULN, alkaline phosphatases < 3 x ULN * No prior or current anticancer treatment to the head and neck area (e.g. radical attempted or tumor reductive surgery, neo-adjuvant chemotherapy, EGFR inhibitors or radiotherapy). * Patients must be candidate for curative intent external beam chemo-radiotherapy, and must be expected to complete the treatment. * All patients should have an oral and dental examination including preferably clinical and radiological examination. Whenever indicated, extraction of dental elements should be carried out at least 10 to 14 days before treatment start. * Radiotherapy planned to start within acceptable delay (preferably within 2 weeks and a maximum of 4 weeks from randomization). * Radiotherapy planned to start within 8 weeks from baseline imaging tumor assessment. * Patients should not have symptoms of peripheral neuropathy, assessed by medical history. * Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial. * All subjects must: * Agree to abstain from donating blood while receiving therapy and for four weeks following discontinuation of therapy. * Agree not to share study medication with another person and to return all unused study drug to the investigator.
Exclusion criteria
Exclusion criteria: The same as the EORTC 1219 trial: * Patients who have received treatment with any investigational drug substance within 4 weeks prior to randomization. * Current participation in any other interventional clinical study. * Pregnant or breast-feeding female patient. Pregnancy test should be done within 72 hours from treatment start. * Female subjects of childbearing potential (defined as a sexually mature woman who 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally post-menopausal (amenorrhoea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)) not willing to use adequate contraception during study and for 6 month after last dose of study drug. * Male subjects not willing to use condoms throughout study drug therapy, and for 6 months after cessation of study therapy if their partner is of childbearing potential and has no contraception. * Known or suspected HIV infection. * Second malignancies in the 3 years prior to study entry with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin. * Uncontrolled or chronic bacterial, fungal or viral infection. * Known or suspected hypersensitivity to component(s) of investigational product or cisplatin contraindication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| •To evaluate FAZA-PET/CT parameters as prognostic factors for the loco-regional control rate at 2 years in HNSCC patients receiving chemo-radiotherapy ± nimorazole. •Time to locoregional recurrence is counted from the day of randomization to the day of the first record of local or regional progression. Distant recurrence, second cancer and death in absence of locoregional recurrence are not considered events of interest. The PET / CT scans objective parameters for hypoxia will be determined within the primary tumor and the pathologic nodes, based on standardized uptake values (SUV), for example: SUVmax, SUVmean, total hypoxic volume x SUVmean. Definition of hypoxia within a tumor on FAZA PET/CT: A hypoxic voxel will be defined as a voxel expressing a SUV equal or above the SUVmean of the posterior contralateral neck muscles plus three standard deviations (Servagi-Vernat S, et al. A prospective clinical study of ¹*F-FAZA PET-CT hypoxia imaging in head and neck squamous cell carcinoma before and during radiation therapy. Eur J Nucl Med Mol Imaging. 2014 Aug;41(8):1544-52.). | — |
Secondary
| Measure | Time frame |
|---|---|
| •To evaluate the change in FAZA uptake at day 14 (14 days after starting chemo-radiotherapy treatment relative to baseline), against patient*s outcome measured by loco-regional control rate at 2 years. •To investigate the agreement between FAZA uptake and 15 gene signatures. Definition of response or non-response by repeated scans (pre-/during treatment): In the patients with tumors having a hypoxic volume at baseline, a threshold of hypoxic volume change will be explored to define the response or non-response, based on patient outcomes (loco-regional control rate at year 2). | — |
Countries
Netherlands
Outcome results
None listed