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

November 2, 2017 updated by: Oliver Riesterer, University of Zurich

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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
  • primary tumor location in oral cavity, oropharynx, hypopharynx or larynx
  • Patients with CUP (cancer of unknown primary) syndrome in case they have advanced lymph node metastases (Tx N2b-3 M0 (N2b only if ≥ 3 ipsilateral nodes involved).- Indication for chemoradiation (RT + Cisplatin)
  • curative treatment intent
  • 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
  • Any neoadjuvant chemotherapy prior to screening
  • Treatment with other investigational drugs within 4 weeks
  • History of malignancy other than basal cell skin cancer unless disease free for a minimum of 3 years.
  • Uncontrolled claudication, bleeding, or thromboembolic disorders at screening
  • Patients receiving heparin, warfarin or phenprocoumon therapy are ineligible- Uncontrolled and severe hypertension at screening according to the judgement of the investigator.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Erbitux®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Locoregional tumor control
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety and tolerability
Time Frame: 2 years
2 years
Progression free survival (PFS)
Time Frame: 2 years
2 years
Overall survival (OS)
Time Frame: 2 years
2 years
Metastasis rate
Time Frame: 2 years
2 years
Metastasis free survival (MFS)
Time Frame: 2 years
2 years
Biological surrogate markers
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Zurich

Investigators

  • Principal Investigator: Oliver Riesterer, Leitender Arzt, University Hospital Zurich, Division of Radiation Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 19, 2011

Primary Completion (Actual)

October 25, 2017

Study Completion (Actual)

October 25, 2017

Study Registration Dates

First Submitted

July 26, 2011

First Submitted That Met QC Criteria

September 15, 2011

First Posted (Estimate)

September 16, 2011

Study Record Updates

Last Update Posted (Actual)

November 6, 2017

Last Update Submitted That Met QC Criteria

November 2, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Add-On cetuximab

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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