A Phase II Study In Patients With Advanced Head And Neck Cancer Of Standard Chemoradiation And Add-On Cetuximab

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2011 by University of Zurich
Sponsor:
Information provided by (Responsible Party):
Oliver Riesterer, University of Zurich
ClinicalTrials.gov Identifier:
NCT01435252
First received: July 26, 2011
Last updated: September 15, 2011
Last verified: September 2011
  Purpose

Sixty patients with advanced squamous cell carcinomas of the head and neck will be enrolled in this study. Patients are treated with standard chemoradiation in combination with concurrent add-on cetuximab. Subsequently patients are randomized to cetuximab consolidation therapy (three months, Arm A) versus no consolidation therapy (Arm B). The aim of this study is to investigate if cetuximab consolidation therapy improves the 2-year locoregional control rate.

  • Trial with medicinal product
  • Trial with radiotherapy

Condition Intervention Phase
Oropharyngeal Cancer
Hypopharyngeal Cancer
Laryngeal Cancer
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Open-Label, Single Center Study In Patients With Advanced Head And Neck Cancer To Investigate Efficacy And Safety Of Standard Chemoradiation And Add-On Concurrent Cetuximab ± Consolidation Cetuximab

Resource links provided by NLM:


Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • Locoregional tumor control [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Metastasis rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Metastasis free survival (MFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Biological surrogate markers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: September 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Patients will be treated with chemoradiation in combination with concurrent cetuximab. Two weeks after end of chemoradiation the consolidation phase will start and patients will receive biweekly consolidation cetuximab, maximally 6 infusions over 12 weeks.
Drug: Cetuximab
Arm A: chemoradiation in combination with concurrent cetuximab Arm B: chemoradiation in combination with concurrent and consolidation cetuximab
Other Name: Erbitux®
Experimental: Arm B
Patients will be treated with chemoradiation in combination with concurrent cetuximab.
Drug: Cetuximab
Arm A: chemoradiation in combination with concurrent cetuximab Arm B: chemoradiation in combination with concurrent and consolidation cetuximab
Other Name: Erbitux®

Detailed Description:

This clinical study translates our preclinical findings that concurrent and consolidation cetuximab improves efficacy of RT into the clinic. It is a phase II, randomized, open-label, single center study in patients with locoregionally advanced stage III-IV and/or total gross tumor volume (tGTV) > 70cc head and neck cancer. This study population is at high risk for locoregional recurrence after chemoradiation alone. Tumor stages to be included are T3-4 Nx, Tx N2b-N3 (N2b only if ≥ 3 ipsilateral nodes involved) M0 and/or tGTV >70 cc (any T, any N, M0) squamous cell cancers of the head and neck (HNSCC). All patients will receive in, the so called 'Induction Phase' standard chemoradiation (RT up to 70 Gy in combination with weekly CDDP 40 mg/m2) and add-on concurrent cetuximab (loading Dose 400 mg/m2, concurrent dose 250 mg/m2 weekly). The patients are randomized to either add-on consolidation cetuximab (500 mg/m2 biweekly x 6 over 12 weeks) (Arm A) or no further treatment (Arm B). Randomization will take place after Induction Phase. The total number of patients to be included into the study is 60 (30 patients per arm). Up to 6 patients may be replaced in case of early drop out to reach that aim.

The sample size of 60 patients is considered to be sufficient to collect first information on clinical efficacy and the possible impact of various biomarkers on clinical endpoints. If the results of this study will demonstrate that the novel treatment regimen is safe and efficacious, a randomized multicenter phase III study will follow.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • T3-4 Nx M0; Tx N2b-3 M0 (N2b only if = 3 ipsilateral nodes involved) and/or total GTV > 70 cc (any T, any N, M0)
  • biopsy proven squamous cell cancer of the oral cavity, oropharynx, hypopharynx or larynx
  • Indication for chemoradiation (RT + Cisplatin)
  • Start of chemoradiation within the recruitment time frame
  • Performance Status WHO/ECOG: 0-1
  • Age between 18 and 75 years
  • No previous chemotherapy or RT for cancer of the head and neck
  • Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment)
  • Patient must sign informed consent prior to study entry.

Exclusion criteria: - Cancer of the nasopharynx

  • History of malignancy other than basal cell skin cancer unless disease free for a minimum of 3 years.
  • History of claudication, bleeding, or thromboembolic disorders.
  • Patients receiving heparin, warfarin or phenprocoumon therapy are ineligible.
  • Blood pressure of systolic >150 mmHg and or diastolic >100 mmHg
  • Current uncontrolled cardiac disease: Unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, history of myocardial infarction within 12 months, significant arrhythmias
  • Left ventricular function < 45 % (determination of left ventricular function required when history of cardiac disease)
  • History of stroke within 6 months
  • Major surgical procedure, or significant traumatic injury within 28 days prior to screening; anticipation of need for major surgical procedure during the course of the study.
  • Acute bacterial or fungal infection requiring intravenous antibiotics at screening
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at screening
  • Pregnant (positive pregnancy test) or lactating
  • Previous organ transplantation
  • Any immune suppressive therapy
  • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition because study treatment might be immuno-suppressive (Note: HIV testing only required if clinically indicated)
  • Any uncontrolled condition, which in the opinion of the investigator, would interfere with the safe and timely completion of study procedures.
  • Preexisting renal insufficiency with impaired creatinine clearance (<60ml/min) and/or increased plasma creatinine (>106 µmol/l) at screening
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to screening
  • Serious, non-healing wound, ulcer, or bone fracture
  • AST, ALT, or bilirubin > 1.5 x normal
  • Preexisting absolute neutrophil count (ANC) < 1,800 cells/mm3
  • Platelets < 100,000 103/µl at screening
  • PTT > 1.5 x normal
  • WBC < 4000 103/µl
  • Hb < 11 g/dl at screening (Note: The use of transfusion or other intervention to achieve Hb > 11 g/dl is possible)
  • Contraindication to CDDP
  • Known allergy to cetuximab or cisplatin, or severe allergic reactions (= Grade 3) to cetuximab loading dose
  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: NCT01435252

Contacts
Contact: Oliver Riesterer, Oberarzt +41442553748 oliver.riesterer@usz.ch

Locations
Switzerland
University Hospital Recruiting
Zurich, Switzerland
Sponsors and Collaborators
University of Zurich
Investigators
Principal Investigator: Oliver Riesterer, Oberarzt University Hospital Zurich, Division of Radiation Oncology
  More Information

No publications provided

Responsible Party: Oliver Riesterer, Oberarzt, University of Zurich
ClinicalTrials.gov Identifier: NCT01435252     History of Changes
Other Study ID Numbers: Add-On cetuximab
Study First Received: July 26, 2011
Last Updated: September 15, 2011
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Hypopharyngeal Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014