Adjuvant Cetuximab and Chemoradiation in Head and Neck Cancer (ACCRA-HN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier:
NCT00791141
First received: November 13, 2008
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

This multicenter, open-label, uncontrolled phase II trial evaluates safety and efficacy of post-operative chemoradiation in combination with cetuximab in squamous cell carcinoma of the head and neck.


Condition Intervention Phase
Head and Neck Cancer
Drug: Cetuximab
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: Multicenter, Open-label Phase II Trial on Post-surgery Chemoradiation in Combination With Cetuximab in Squamous Cell Carcinoma of the Head and Neck With High Risk of Locoregional Recurrence.

Resource links provided by NLM:


Further study details as provided by Heinrich-Heine University, Duesseldorf:

Primary Outcome Measures:
  • Rate of patients experiencing grade 3/4 acute toxicities not considering grade 3/4 skin tox. outside the radiation portals combined with 2-years disease-free survival rate. [ Time Frame: any toxicities occurring within 90 days post radiation start ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of Loco-regional relapse [ Time Frame: assessment after patient has completed follow-up ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: time from start of surgery to the first evidence of loco-regional or distant tumor relapse or death ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: from start of surgery to the first observation of disease progression or death ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: censored at the time of last documented efficacy ] [ Designated as safety issue: No ]
  • The rate of patients with secondary primary neoplasm [ Time Frame: assessment after patient has completed follow-up ] [ Designated as safety issue: Yes ]
  • The incidence of late toxicity [ Time Frame: beyond 90 days after start of radiation therapy ] [ Designated as safety issue: Yes ]

Enrollment: 80
Study Start Date: August 2008
Study Completion Date: September 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab
Cetuximab in combination with radiotherapy, cisplatin and 5-FU. After chemoradiotherapy all patients receive a cetuximab maintenance therapy.
Drug: Cetuximab
Loading dose prior to chemoradiotherapy 400 mg/m², followed by every week infusion of 250 mg/m² during chemoradiotherapy. After chemoradiotherapy every 2 week infusions of 500 mg/m² over 6 months.
Other Name: Erbitux

Detailed Description:

Advanced squamous cell carcinoma of the head and neck still has a poor prognosis and loco-regional recurrence frequently occurs. Efforts have been made to improve response rates and survival and different therapeutic regimens including concurrent chemo-radiotherapy or sequential chemo-radiotherapy have been developed.

To further increase the outcome of patients with locally advanced SCCHN effective new treatments with minimal toxicities are needed. Molecular targeted agents, which do not demonstrate overlapping toxicities with commonly used chemotherapy agents, have therefore been investigated. The EGFR is widely expressed at high levels in SSCHN and is associated with poor prognosis.

Cetuximab has already been investigated in combination with radiotherapy or chemotherapy in patients with head and neck cancer. The immunoradiotherapy was well tolerated with most of the side effects related to the high dose irradiation. The most common side effects are mucositis and dysphagia. Additionally, skin reactions appear sometimes more frequently in cetuximab administration. Grade 3 to 4 infusion reactions were observed in 3% of the patients treated with cetuximab. Based on the current promising results with RCT in patients with locally advanced head and neck cancer and clinical results with EGFR-antibodies plus RT, the present study was primarily designed to define the acute grade 3/4 toxicity.

We expect to show effective results in reducing the risk of distant metastasis, with administration of an additional six month adjuvant cetuximab treatment, in patient with recurrent SCCHN.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed written informed consent;
  • Males or females between 18 and 70 years of age;
  • Surgically resected squamous cell carcinomas of the hypopharynx, oropharynx, larynx and oral cavity with high risk of locoregional recurrence not more than 6-9 weeks (maximum) ago;
  • To be categorized as high risk patients have to fulfil at least one of the following criteria:

    • R0 - resection <5 mm margin
    • R1 - resection
    • Extracapsular nodal extension;
  • no previous chemotherapy, radiotherapy;
  • Performance status ECOG: 0 - 1;
  • Contraception in male and female patients if of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing;
  • Adequate renal, liver and hematological functions (within maximum 9 weeks until surgery):

    • Adequate bone marrow function: neutrophils > 1.5 x 10^9/L, platelets > 100 x 10^9/L, hemoglobin > 10.0 g/dL
    • Adequate liver function: Bilirubin < 2.0 mg/dL, AST, ALT, AP, γ-GT < 3 x ULN
    • Adequate renal function: creatinine clearance > =60 ml/min
  • No distant metastases;

Exclusion Criteria:

  • Nasopharyngeal carcinoma;
  • R2 resection;
  • Invalid informed consent;
  • Performance Status > 1;
  • Previous chemotherapy or radiotherapy for carcinoma of the head and neck;
  • Prior exposure to EGFR pathway targeting therapy;
  • Other serious illness or medical conditions:

    • Unstable cardiac disease despite treatment, congestive heart failure NYHA grade 3 and 4;
    • Clinically significantly abnormal electrocardiogram (ECG) or left ventricular ejection fraction (LVEF) below the institutional range of the normal
    • Significant neurologic or psychiatric disorders including dementia or seizures;
    • Active uncontrolled infection;
    • Active disseminated intravascular coagulation;
    • Other serious underlying medical conditions which could impair the ability of the patient to participate in the study;
  • Symptomatic peripheral neuropathy National Cancer Institute-Common Toxicity Criteria (NCI-CTC v3.0) grade 2 or ototoxicity grade 2, except if due to trauma or mechanical impairment due to tumor mass;
  • Having participated in another therapeutic clinical trial or any investigational agent in the preceding 30 days;
  • Known allergic/hypersensitivity reaction to any of the components of the treatment;
  • Pregnancy (absence confirmed by serum/urine β-HCG) or breast-feeding;
  • Known drug abuse;
  • Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix;
  • Legal incapacity or limited legal capacity;
  • Sensitivity and incompatibility against 5-Fluorouracil
  • Sensitivity and incompatibility against platinum-compounds
  • Known incompatibilities >grade 3 towards cetuximab
  • expected incompliance of patient (e.g. in case of severe alcohol addiction)
  • Dental evaluation: Pre treatment dental care before start of radiochemotherapy (approximately 8 to 10 days lapse-time is needed for complete recovery before initiation of radiation therapy).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00791141

Locations
Germany
Department of Radiotherapy and Radiological Oncology, University Hospital Munich
Munich, Bavaria, Germany, 81377
Department of Radiotherapeutics of the University Hospital Freiburg
Freiburg, BW, Germany, 79106
Department of Radiological Oncology University Hospital Heidelberg
Heidelberg, BW, Germany, 69120
Department of Radiotherapy and Radiological Oncology University Hospital Tuebingen
Tuebingen, BW, Germany, 72076
Department of Radiotherapy and Radiological Oncology University Hospital Ulm
Ulm, BW, Germany, 89091
Department of Radiotherapy an Radiological Oncology University Hospital Essen
Essen, NW, Germany, 45122
Department of Radiotherapy and Radiological Oncology University Hospital Mainz
Mainz, Rheinland-Pfalz, Germany, 55131
Department of Radiotherapy, University Hospital Schleswig Holstein, Campus Lübeck
Lübeck, Schleswig Hostein, Germany, 23538
Department of Radiotherapy and Radiological Oncology Universität Hospital Jena
Jena, Thueringen, Germany, 07743
Charité University Medicine, Department of Radiotherapy and Radiological Oncology
Berlin, Germany, 13353
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
Investigators
Principal Investigator: Wilfried Budach, Prof. Dr. Department of Radiotherapy and Radiological Oncology
  More Information

Publications:
Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT00791141     History of Changes
Other Study ID Numbers: ACCRA-HN
Study First Received: November 13, 2008
Last Updated: January 22, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Heinrich-Heine University, Duesseldorf:
Head and Neck Cancer
Radiation therapy
Chemotherapy
Chemoradiotherapy
adjuvant cetuximab administration

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014