Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy

Phase 2UnknownNCT01192087

Heidelberg University49 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: 6 weeks post completion of therapy

Number of Participants with late adverse effects as a Measure of toxicity

Time frame: 3 years post completion of treatment

Secondary Outcomes

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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: at 3 years post treatment

Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts