cancer of oesophagus
Conditions
Interventions
Experimental arm (arm A): Chemo-radiation therapy (50.4 Gy/1.8 Gy per fraction
+ i.v. cisplatin 75 mg/m2 (day 1) and i.v. 5-FU 1000 mg/m2 (day 1-4) in
treatment week 1 and 5) combined with i.v. pani
Sponsors
Universitair Medisch Centrum Sint Radboud
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: -Age 18 - 70 years -Histologically proven SCC or adenocarcinoma of the oesophagus -No proven (distant) metastases (ultrasonography, CT or MRI) -No prior treatment for carcinoma of the oesophagus -Karnofsky performance status >=70% (appendix A) -Irresectable disease as assessed by the multidisciplinary tumour board -All patients (male and female) must use effective contraception methods according to CPMP/ICH/286/95 if of reproductive potential (e.g. implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner), for the whole duration of the study and until six months after they received the last treatment dose -No contraindications for cytotoxic therapy or panitumumab: -No known hypersensitivity/allergy to any of the compounds used -Haematology: *Neutrophil count >= 1.5*109 /L *Thrombocyte count >= 100*109 /L *Haemoglobin >= 6.2 mmol/L (100 g/L) -No known HIV infection or other condition of persistent immunodeficiency -Renal function: *Creatinine clearance (MDRD) >= 60 mL/min -Hepatic function: *Total bilirubin = lower limit of normal (LLN) *Magnesium >= LLN -History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan. -No known other serious illness or medical condition present at entry in the study including: * Unstable cardiac disease despite treatment, congestive heart failure NYHA grade 3 and 4 * Clinically significantly abnormal electrocardiogram (ECG) or left ventricular ejection fraction (LVEF) below the institutional ULN * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) = grade 2 -Ototoxicity (CTCAE v3.0 any term in *auditory/ear*) >= grade 2 except if due to trauma or mechanical impairment due to tumour mass -Other serious underlying medical condition which could impair the ability of the patient to participate in the study -No or insufficient oral nutrient intake -No prior exposure to EGFR pathway targeting agents -No known drug abuse -Absence of any psychological, familial, sociological (e.g. severe alcohol addiction expected to hamper protocol compliance) or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial -No participation in another interventional clinical trial in the preceding 30 days -Written informed consent to participate to study must be given according to ICH/GCP, and national/local regulations.
Exclusion criteria
Exclusion criteria: -Prior treatment for this tumour -Prior treatment with radiation therapy in the area of the oesophagus or other site that will interfere with proposed treatment -Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment. -Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment. -History of other prior malignancy in past 5 years, other than basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ;Exclusion criteria for the PET-scan -Severe claustrophobia -Diabetes mellitus (type I and II) -Serum glucose level >11 mmol/L
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1-year overall survival | — |
Secondary
| Measure | Time frame |
|---|---|
| * toxicity * progressie-free-survival and respons rate * 1-years overall survival in KRAS-wt patients * pharmacodynamics (PD) of panitumumab (EGFR, K-RAS, B-RAF, downstream signalling pathways ) compared between the biopsy at baseline (standard) and the biopsy one week after start chemo-radiation therapy * Quantification of baseline FDG uptake (SUV) with PET, and SUV changes (ΔSUV) (in 35 patienten per arm) baseline 7 days after the first panitumumab dose or for start chemo-radiation therapy. during treatment with chemoradiation therapy after three weeks. 2-4 weeks after finishing treatment. 10-12 weeks after finishing treatment * Correlation PET results with respons rate and PD of panitumumab * CTCs and CECs at baseline, after 2 weeks during chemo-radiation therapy and 12 weeks after finishing treatment. | — |
Countries
Netherlands
Outcome results
None listed