Chemoradiation Treatment for Head and Neck Cancer

A Phase II Study of Cetuximab, Carboplatin and Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

This is a Phase II study of cetuximab, carboplatin and radiotherapy (RT) in patients with Locally Advanced Head and Neck Carcinomas (LAHNC) who are unfit for cisplatin.

The aim of this study is to show the feasibility and safety profile of the combination of cetuximab, carboplatin and RT in treatment of patients with LAHNC.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Cetuximab; Drug: Carboplatin; Radiation: Radiotherapy

Detailed Description

Secondary objectives are to estimate failure free survival (FFS) and overall survival, to evaluate the time to local and regional failure and to determine the site of first failure (characterised as local, regional, distant or combinations). Acute and late treatment toxicities will also be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previously untreated SCC of the oropharynx, larynx or hypopharynx.
• Stage III or IV, excluding T1N1, and metastatic disease (to be confirmed by a chest CT, and abdominal CT or ultrasound scan if patients with abnormal liver function tests or a bone scan or FDG-PET if patients with bone pain).
• Histologically or cytologically confirmed HNSCC
• Disease must be considered potentially curable by chemoradiation

• Patients medically unfit for cisplatin chemotherapy due to one or more of the following reasons:

  • Clinically significant sensori-neural hearing impairment (audiometric abnormalities without corresponding clinical deafness will not be regarded as a contraindication to cisplatin)
  • Severe tinnitus
  • Renal impairment (GFR < 60ml/min)
  • Peripheral neuropathy > grade 2
  • Inability to tolerate intravenous hydration eg due to cardiac disease
  • Co-morbidities (based on clinical judgement by the investigator) associated with ECOG PS 2 that in the view of the investigator would preclude the safe administration of cisplatin
• Performance status ECOG 0, 1 or 2.

• Adequate haematological, renal and hepatic functions as defined by:

  • Absolute neutrophil count (ANC, segmented cells (segs) + bands)>= 1.5 x 109/L
  • Platelet count >= 100 x 109/L
  • Total bilirubin <= 1.5 x upper normal limit
  • Alanine aminotransferase <= 2.5 x upper normal limit
  • Calculated creatinine clearance > 40ml/min (Cockcroft-Gault formula).
  • If calculated creatinine clearance < 50 ml/min, glomerular filtration rate to be measured with DTPA or EDTA scan. If < 40 ml/min not eligible.
• Age >18 years
• Signed written consent
• Suitable for follow-up for 4 years in the view of the investigator

Exclusion Criteria:

• Distant metastases, i.e., any metastatic disease below the clavicles. Patients with lung nodules >10mm will be excluded unless non-malignancy aetiology is established. Patients with lesions 5-10mm can be included if a FDG-PET scan is negative and the investigator considers on clinical grounds that metastasis is unlikely. Patients with lesions < 5mm can be included if the investigator considers on clinical grounds that metastases are unlikely. Patients with multiple lung nodules should not be included unless there is a strong case that these do not represent metastases, e.g., stable on imaging for over 12 months, non-malignant aetiology apparent. The level of clinical suspicion may be influenced by clinical stage, e.g., N3 disease, low neck nodes. In general if there is any doubt patients should be excluded.
• Previous radical RT to the head & neck region, excluding superficial RT for a non-melanomatous skin cancer.
• Patients with prior cancers, except: those diagnosed > 5 years ago with no evidence of disease recurrence and clinical expectation of recurrence of less than 5%; or successfully treated non-melanoma skin cancer; or carcinoma in situ of the cervix.
• Significant intercurrent illness that will interfere with the chemotherapy or radiation therapy such as HIV infection, cardiac failure, pulmonary compromise, active infection
• Any history of myocardial infarction, ventricular arrhythmias, or unstable angina within the last 6 months
• Pregnant or lactating women.
• Weight loss greater than 20 % of usual body weight in the 3 months preceding trial entry
• High risk for poor compliance with therapy or follow up as assessed by the investigator
• Prior radiation to greater than 30% of the bone marrow
• Prior systemic chemotherapy for cancer
• Refusal by male or female patients, to use appropriate contraception during the study and for 3 months afterwards
• Any condition or circumstance which might prevent the patient being able to give valid informed consent, or from completing participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single arm; Chemoradiation (Cetuximab, Carboplatin and Radiotherapy)

Drug: Cetuximab; Patients will receive weekly intravenous cetuximab (initial dose 400mg/m2 in the week prior to commencing radiotherapy, then weekly 250mg/m2)for the duration of the radiotherapy; Other Names: Erbitux; Drug: Carboplatin; Weekly intravenous carboplatin (AUC 2) for the duration of the RT; Other Names: Paraplatin; Radiation: Radiotherapy; The radiotherapy schedule will be the "infield boost" (IFB) regimen, that is 66 Gy in 35 fractions over 5 weeks: daily for 3 weeks, then twice daily for 2 weeks (or 70 Gy in 35 fractions over 7 weeks for a specific subgroup of patients where IFB is not recommended).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and Feasibility	An initial 6 patients will be treated. Once all these patients have a 2 week post RT review there will be analysis. If <= 1 patient has a DLT than the treatment is deemed safe.

Secondary Outcome Measures

Outcome Measure	Time Frame
Failure free survival (FFS)	All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment.
Time to local and/or regional failure	All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment.
Overall survival	All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment.
Site of first failure	All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment.
Acute and late treatment toxicities	All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment.

Collaborators and Investigators

• Sponsor: Trans Tasman Radiation Oncology Group
• Investigators: Study Chair: June Corry, Peter MacCallum Cancer Centre, Australia; Study Chair: Danny Rischin, Peter MacCallum Cancer Centre, Australia

Publications and helpful links

Helpful Links

• Click here for more information about this study on the TROG official website

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 22, 2008
• First Submitted That Met QC Criteria: June 22, 2008
• First Posted (Estimate): June 25, 2008

Study Record Updates

• Last Update Posted (Actual): July 12, 2017
• Last Update Submitted That Met QC Criteria: July 10, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Radiotherapy; Carboplatin; Cetuximab; Head and Neck
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Carboplatin; Cetuximab
• Other Study ID Numbers: TROG 07.04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No