Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy

Study Overview
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Brief Summary
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The ACCEPT (A(denoid) c(ystic) c(arcinoma), E(rbitux, and) p(article) t(herapy))-trial is a prospective, monocentric phase I/II feasibility trial evaluating toxicity and efficacy in the combined treatment of intensity-modulated radiation therapy (IMRT) and carbon ion (C12) boost with the epidermal growth factor receptor (EGFR) antibody cetuximab. The primary objective of the study is to explore the toxicity of the combined modality regimen consisting of heavy ion therapy / IMRT and EGFR antibody immunotherapy, by assessing the rate of patients with mucositis or any other toxicity of severity grade 3 or 4 according to NCI CTCAE V. 4. Secondary endpoints include local control, distant control, overall disease-free survival, overall survival

Detailed Description
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Treatment with novel radiotherapeutic technologies could increase local control in adenoid cystic carcinoma of the head and neck. Especially combined treatment with intensity-modulated radiation therapy and heavy ion (C12) boost to the primary tumor or previous tumor bed could be established as the treatment of choice in this disease. Unfortunately, therapeutic results in the treatment of adenoid cystic carcinoma are still hampered by the occurrence of distant metastases (predominantly in the lungs) which, though progressing comparatively slowly, still limit the patient's life expectancy. Most adenoid cystic carcinomas (> 80%) though, exhibit over-expression of EGFR receptors and hence provide an approach for systemic treatment. In this prospective phase II trial, the application of the EGFR antibody cetuximab will be evaluated in combination with the established treatment of intensity-modulated radiation therapy plus C12 heavy ion boost. The trial aims at evaluation of toxicity and feasibility of the combined treatment, as primary endpoint, as well as local control and disease-free survival as secondary endpoints.

Official Title
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Combined Treatment of Adenoid Cystic Carcinoma With Cetuximab and IMRT Plus C12 Heavy Ion Boost - ACCEPT - (ACC, Erbitux, and Particle Therapy); Phase I/II Feasibility Study

Conditions
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Adenoid Cystic Carcinoma

Intervention / Treatment
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* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Histologically proven, or surgically resected adenoid-cystic carcinoma of the head and neck and macroscopic or microscopic residual tumor (R1/ R2) or Tumor stage >T3/T4 or perineural invasion and M0 stage Written informed consent Age between 18 and 70 years Karnofsky Index ≥ 70% Adequate bone-marrow, liver, and kidney function: neutrophils ≥ 1.5 x 109/L, thrombocytes ≥ 100 x 109/L, haemoglobin ≥ 10.0 g/dL bilirubin ≤ 2.0 g/dL SGOT, SGPT, AP, gamma-GT ≤ 3 x ULN serum creatinine ≤ 1.5 mg/dL effective contraception Exclusion Criteria: Prior RT or chemotherapy for tumors of the head and neck R0 resection M1 (distant metastases) prior immunotherapy signs of active infection other serious illnesses Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias) Significant neurologic or psychiatric disorders including dementia or seizures Active disseminated intravascular coagulopathies Other serious underlying medical conditions prohibiting the patient's participation in the trial according to the judgement of the investigators Active participation in another clinical trial within the past 30 days Known allergic/ hypersensitivity reactions to non-human proteins Women: pregnant (Positive serum/ urine beta-HCG ) or breast-feeding, Known drug abuse, Other previous malignancy within the past 5 years, with exception of a history of a previous, adequately treated, basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix, Legal incapacity or limited legal capacity, Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab arm<br>patients receive weekly cetuximab in combination with IMRT and carbon ion boost | Drug: Cetuximab<br>* cetuximab initial dose (7 days prior to RT treatment start): 400 mg/m² body surface cetuximab weekly doses (from RT treatment start throughout radiation treatment): 250 mg/m² body surface<br>* Other names: Cetuximab (Erbitux);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with acute adverse effects as a Measure of toxicity | The primary objective is to explore the toxicity of the combined treatment consisting of heavy ion therapy / IMRT and cetuximab by assessing the rate of patients with mucositis or any other toxicity of severity grade 3 or 4 according to NCI CTCAE V. 4. Acute treatment effects will be evaluated 6 weeks and late effects 3 years post completion of treatment | 6 weeks post completion of therapy | 
| Number of Participants with late adverse effects as a Measure of toxicity | The primary objective is to explore the toxicity of the combined treatment consisting of heavy ion therapy / IMRT and cetuximab by assessing the rate of patients with mucositis or any other toxicity of severity grade 3 or 4 according to NCI CTCAE V. 4. Acute treatment effects will be evaluated 6 weeks and late effects 3 years post completion of treatment | 3 years post completion of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local relapse-free survival | Local relapse-free survival will be defined as the time from the initial dose of study therapy to the time of locoregional disease progression or relapse or death, or to the date of last assessment without any such event (censored observation) | at 3 years post treatment | 
| distant relapse-free survival | Distant relapse-free survival will be defined as the time from the initial dose of study therapy to the time of distant metastasis detection or death, or to the date of last assessment without any such event (censored observation) | at 3 years post treatment | 
| overall disease-free survival | Distant disease-free survival will be defined as the time from the initial dose of study therapy to the time of any detection of adenoid cystic carcinoma relapse or development of secondary cancer or death, or to the date of last assessment without any such event (censored observation) | at 3 years post treatment | 
| overall survival | The duration of survival will be determined by measuring the time interval from initial dose of study therapy to the date of death of any cause or last observation (censored) | at 3 years post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenoid cystic carcinoma, carbon ion therapy, IMRT (intensity-modulated therapy), radioimmunotherapy, Cetuximab