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Adenoid Cystic Carcinoma, Erbitux, and Particle Therapy (ACCEPT)

This study is currently recruiting participants.
Verified April 2013 by University of Heidelberg
Sponsor:
Collaborators:
Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany
University Hospital Heidelberg
Merck KGaA
Information provided by:
University of Heidelberg
ClinicalTrials.gov Identifier:
NCT01192087
First received: August 30, 2010
Last updated: April 23, 2013
Last verified: April 2013
History of Changes
  Purpose

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 Intervention Phase
Adenoid Cystic Carcinoma
 Drug: Cetuximab
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Drug Information available for: Cetuximab
U.S. FDA Resources

Further study details as provided by University of Heidelberg:

Primary Outcome Measures:
  • Number of Participants with acute adverse effects as a Measure of toxicity [ Time Frame: 6 weeks post completion of therapy ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: 3 years post completion of treatment ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: at 3 years post treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 3 years post treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 3 years post treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 3 years post treatment ] [ Designated as safety issue: No ]
    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)


Estimated Enrollment: 49
Study Start Date: June 2012
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Cetuximab (Erbitux)

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01192087

Contacts
Contact: Alexandra D Jensen, MD MSc +49-6221-56- ext 8202 alexandra.jensen@med.uni-heidelberg.de
Contact: Marc W Münter, MD +49-6221-56- ext 8202 marc.muenter@med.uni-heidelberg.de

Locations
Germany
Dept. of Radiation Oncology Recruiting
Heidelberg, Germany, 69120
Contact: Aleandra D Jensen, MD MSc     +49-6221-56 ext 8202     alexandra.jensen@med.uni-heidelberg.de    
Sub-Investigator: Alexandra D Jensen, MD MSc            
Sponsors and Collaborators
University of Heidelberg
Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany
University Hospital Heidelberg
Merck KGaA
Investigators
Principal Investigator: Jürgen Debus, Prof. Dr. Dr. Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Prof. Dr. Dr. J. Debus, Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, Germany
ClinicalTrials.gov Identifier: NCT01192087     History of Changes
Other Study ID Numbers: ACCEPT
Study First Received: August 30, 2010
Last Updated: April 23, 2013
Health Authority: Germany: Paul-Ehrlich-Institut
Germany: Federal Office for Radiation Protection

Keywords provided by University of Heidelberg:
adenoid cystic carcinoma
carbon ion therapy
IMRT (intensity-modulated therapy)
radioimmunotherapy
Cetuximab

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Adenoid Cystic
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
 Adenocarcinoma
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013