Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy

Brief Title

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

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.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

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

Secondary Outcome

 local relapse-free survival

Condition

Adenoid Cystic Carcinoma

Intervention

Cetuximab

Study Arms / Comparison Groups

 Cetuximab arm

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

49

Start Date

June 2012

Completion Date

July 2017

Primary Completion Date

July 2015

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
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

Jürgen Debus, Prof. Dr. Dr., +49-6221-56-, [email protected]

Location Countries

Germany

Location Countries

Germany

NCT ID

NCT01192087

Organization ID

ACCEPT

Study Sponsor

Heidelberg University

Collaborators

 Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany

Study Sponsor

Jürgen Debus, Prof. Dr. Dr., Principal Investigator, Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany

Verification Date

April 2013