Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy

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

Sex

All

Minimum age

18 Years

Maximum age

70 Years

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

• BACKGROUNDChen AM, Bucci MK, Weinberg V, Garcia J, Quivey JM, Schechter NR, Phillips TL, Fu KK, Eisele DW. Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):152-9. doi: 10.1016/j.ijrobp.2006.04.014. PMID 16904520
• BACKGROUNDMunter MW, Schulz-Ertner D, Hof H, Nikoghosyan A, Jensen A, Nill S, Huber P, Debus J. Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment. Radiat Oncol. 2006 Jun 6;1:17. doi: 10.1186/1748-717X-1-17. PMID 16756669
• BACKGROUNDSchulz-Ertner D, Nikoghosyan A, Didinger B, Munter M, Jakel O, Karger CP, Debus J. Therapy strategies for locally advanced adenoid cystic carcinomas using modern radiation therapy techniques. Cancer. 2005 Jul 15;104(2):338-44. doi: 10.1002/cncr.21158. PMID 15937907
• BACKGROUNDSchulz-Ertner D, Nikoghosyan A, Thilmann C, Haberer T, Jakel O, Karger C, Kraft G, Wannenmacher M, Debus J. Results of carbon ion radiotherapy in 152 patients. Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):631-40. doi: 10.1016/j.ijrobp.2003.09.041. PMID 14751537
• BACKGROUNDSchulz-Ertner D, Nikoghosyan A, Jakel O, Haberer T, Kraft G, Scholz M, Wannenmacher M, Debus J. Feasibility and toxicity of combined photon and carbon ion radiotherapy for locally advanced adenoid cystic carcinomas. Int J Radiat Oncol Biol Phys. 2003 Jun 1;56(2):391-8. doi: 10.1016/s0360-3016(02)04511-x. PMID 12738314
• BACKGROUNDJakel O, Kramer M, Schulz-Ertner D, Heeg P, Karger CP, Didinger B, Nikoghosyan A, Debus J. Treatment planning for carbon ion radiotherapy in Germany: review of clinical trials and treatment planning studies. Radiother Oncol. 2004 Dec;73 Suppl 2:S86-91. doi: 10.1016/s0167-8140(04)80022-7.