Clinical trial NCT01192087: Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Adenoid Cystic Carcinoma
Keywords: adenoid cystic carcinoma
carbon ion therapy
IMRT (intensity-modulated therapy)
radioimmunotherapy
Cetuximab
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany
name: University Hospital Heidelberg
name: Merck KGaA, Darmstadt, Germany
First posted: 2010-08-31
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with acute adverse effects as a Measure of toxicity
timeFrame: 6 weeks post completion of therapy
measure: Number of Participants with late adverse effects as a Measure of toxicity
timeFrame: 3 years post completion of treatment
Secondary outcomes:
measure: local relapse-free survival
timeFrame: at 3 years post treatment
measure: distant relapse-free survival
timeFrame: at 3 years post treatment
measure: overall disease-free survival
timeFrame: at 3 years post treatment
measure: overall survival
timeFrame: at 3 years post treatment
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Dept. of Radiation Oncology
Study officials:
affiliation: Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany
name: Jürgen Debus, Prof. Dr. Dr.
role: PRINCIPAL_INVESTIGATOR
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