ACCEPT: Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy

Sponsor

Heidelberg University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01192087

Collaborator

Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany (Other), University Hospital Heidelberg (Other), Merck KGaA, Darmstadt, Germany (Industry)

Enrollment

Location

Arm

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Adenoid Cystic Carcinoma	Drug: Cetuximab	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

49 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2012

Anticipated Primary Completion Date :

Jul 1, 2015

Anticipated Study Completion Date :

Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cetuximab arm patients receive weekly cetuximab in combination with IMRT and carbon ion boost	Drug: Cetuximab 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 Other Names: Cetuximab (Erbitux)

Arm

Intervention/Treatment

Experimental: Cetuximab arm

patients receive weekly cetuximab in combination with IMRT and carbon ion boost

Drug: Cetuximab

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

Other Names:

Cetuximab (Erbitux)

Outcome Measures

Primary Outcome Measures

Number of Participants with acute adverse effects as a Measure of toxicity [6 weeks post completion of therapy]
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
Number of Participants with late adverse effects as a Measure of toxicity [3 years post completion of treatment]
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

Secondary Outcome Measures

local relapse-free survival [at 3 years post treatment]
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)
distant relapse-free survival [at 3 years post treatment]
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)
overall disease-free survival [at 3 years post treatment]
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)
overall survival [at 3 years post treatment]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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