Post-operative Concurrent Chemo-radiotherapy Versus Post-operative Radiotherapy for Cancer of the Head and Neck

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Trans-Tasman Radiation Oncology Group (TROG)
Sponsor:
Collaborators:
Princess Alexandra Hospital, Brisbane, Australia
The Royal Australian and New Zealand College of Radiologists
Information provided by (Responsible Party):
Trans-Tasman Radiation Oncology Group (TROG)
ClinicalTrials.gov Identifier:
NCT00193895
First received: September 13, 2005
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

The primary objective of the trial is to determine, in patients who have undergone surgery with curative intent for high-risk CSCC of the head and neck, whether there is a difference in time to loco-regional relapse between patients treated with post-operative concurrent chemo-radiotherapy ,consisting of Carboplatin, and post-operative radiotherapy alone. The target sample size for the trial is 266 patients and will take 3-4 years to accrue, based on an anticipated accrual of 80 patients/year. A further 2 years follow up is required.


Condition Intervention Phase
Skin Cancer
Drug: Carboplatin
Radiation: Radiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Post-operative Concurrent Chemo-radiotherapy Versus Post-operative Radiotherapy in High-risk Cutaneous Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by Trans-Tasman Radiation Oncology Group (TROG):

Primary Outcome Measures:
  • Loco-regional Control [ Time Frame: The date of primary outcome analysis will occur when the final patient has reached a minimum 2 years follow-up. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease Free Survival [ Time Frame: The date of analysis will occur when the final patient has reached a minimum 2 years follow-up. ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: The date of analysis will occur when the final patient has reached a minimum 2 years follow-up. ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: The date of analysis will occur when the final patient has reached a minimum 2 years follow-up. ] [ Designated as safety issue: No ]
  • Treatment-related Late Effects [ Time Frame: The date of analysis will occur when the final patient has reached a minimum 2 years follow-up. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 350
Study Start Date: April 2005
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Radiotherapy alone
Radiotherapy alone (60Gy or 66Gy in 30-33 fractions 5-5/week)
Radiation: Radiotherapy
60 Gy OR 66Gy in 2Gy/fraction 5days/week
Other Name: Radiation
Experimental: Radiotherapy plus chemotherapy
Radiotherapy plus chemotherapy (Radiotherapy 60Gy or 66Gy in 30-33 fractions 5/week + Carboplatin (AUC 2) intravenously weekly)
Drug: Carboplatin
Carboplatin will commence with a dose calculated to target an AUC of 2.0. A maximum of 6 doses of weekly Carboplatin will be given. Carboplatin will be administered intravenously over 20-30 minutes prior to radiation therapy.
Other Name: Carboplatin Ebewe, Injection
Radiation: Radiotherapy
60 Gy OR 66Gy in 2Gy/fraction 5days/week
Other Name: Radiation

Detailed Description:

Two in every 3 Australians will be affected by skin cancer over their lifetime. The prevalence of skin cancer will continue to increase due to the ageing population and represents a significant problem in our community. Cure of early (T1-2) de novo cutaneous squamous cell carcinoma (CSCC) treated with either curative intent surgery or radiotherapy is 85-100%. However, the cure rate for locally advanced, recurrent, or metastatic disease to regional nodes following surgery alone are much lower, in the order of 20-70%. Metastatic CSCC is the most common malignancy of the parotid region in Australia. The 5 year loco-regional control with surgery alone is in the order of 40%-45%. The addition of post-operative radiotherapy improves loco-regional control by 15-20%, and is therefore considered the standard of care in this group of patients.

Recent data have shown that synchronous post-operative chemo-radiotherapy is superior to post-operative radiotherapy alone in "high-risk" mucosal head and neck squamous cell carcinoma (HNSCC). However, to date, there is no evidence from randomised trials that such a benefit exists in CSCC of the head and neck. At present there is little consensus amongst clinicians in Australia as to who should receive post-operative chemo-radiotherapy in CSCC. Although tumour control rates may be improved, the addition of chemotherapy may also significantly increase treatment related toxicity. Nonetheless, some centres have adopted the use of post-operative chemo-radiotherapy in selected patients with CSCC based on extrapolation from mucosal sites. This has resulted in a wide variability in practice for this disease.

Australia is uniquely placed to perform such a trial comparing post-operative chemo-radiotherapy to post-operative radiotherapy alone in high-risk CSCC due to the high rate of skin cancer. Currently there are limited data to guide management of patients with resected CSCC who are at high risk for recurrence. While it is reasonable to hypothesize that concurrent chemotherapy in this setting will confer a similar benefit to that seen in mucosal HNSCC, this can only be established by a randomized trial as proposed. If the addition of chemotherapy is shown to be beneficial and safe, then these results are likely to be translated into standard practice both nationally and internationally quite rapidly. On the other hand, if the treatment is found to be ineffective then patients will be spared the unnecessary toxicity and inconvenience associated with the addition of chemotherapy. A further important aspect of this trial will be the assessment of patient-related outcomes using a validated quality of life questionnaire. It will be important to ascertain whether any improvement in locoregional control due to the addition of chemotherapy, is also associated with improvement in quality of life compared to the control arm.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven SCC
  • Patients have undergone either:

    • Resection of the primary lesion
    • Any type of parotidectomy (superficial, total, partial, etc.)
    • Any type of neck dissection(s)
  • High risk feature(s); Advanced primary disease or high risk nodal disease

High Risk Nodal Disease

  • Intra-parotid nodal disease (any number or size, with/without extracapsular extension, with/without an identifiable index lesion)
  • Cervical nodal disease with a synchronous index lesion or previously resected cutaneous primary tumour (<5 years) within the corresponding nodal drainage and a mucosal primary has been excluded with at least a CT +/- MRI and panendoscopy* *For cervical nodal disease to be eligible there must be at least one of the following criteria:

    • > 2 nodes
    • largest node > 3 cm
    • Extracapsular extension

Advanced Primary Disease (TNM 6th Edition 2002) (Appendix 1)

  • T3-4 primary disease (cartilage, skeletal, muscle, bone involvement, > 4 cm) of the head and neck including lip, nose and external auditory canal with or without nodal disease
  • In transit metastases (metastases between the primary site and the adjoining nodal basin)

    • Age > 18 years
    • Written informed consent
    • ECOG <= 2
    • Absolute neutrophil count > 1.5 X 10^9/L, platelet count > 100 X 10^9/L, and haemoglobin > 10 g/dL (pre-radiotherapy blood transfusion to elevate the haemoglobin > 10 g/dL is permissible)
    • Calculated creatinine clearance (Cockcroft-Gault) >= 40 mL/min
    • Available for follow-up for up to 5 years
    • Life expectancy greater than 6 months

Exclusion Criteria:

  • Intercurrent illness that will interfere with either the chemotherapy or radiotherapy such as immunosuppression due to medication or medical condition
  • Metastasis(es) below the clavicles
  • Previous radical radiotherapy to the head and neck, excluding treatment of an early glottic cancer greater than or equal to 2 years ago and superficial radiotherapy to cutaneous SCC or Basal cell carcinoma
  • High risk for poor compliance with therapy or follow-up as assessed by investigator
  • Pregnant or lactating women
  • 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 Level 1 cutaneous melanomas or early glottic cancer > 2 years ago; or non-melanoma skin cancer; or carcinoma in situ of the cervix.
  • Low risk cervical nodal disease* without advanced primary disease

    *Low risk cervical nodal disease is defined as the presence of all of the following criteria:

  • single nodal metastasis
  • greater then or equal to 3cm,
  • no extracapsular extension
  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: NCT00193895

Contacts
Contact: Sandro Porceddu +61 7 3240 2111 sandro_porceddu@health.qld.gov.au

Locations
United States, Florida
University of Florida Shands Cancer Centre Not yet recruiting
Gainesville, Florida, United States, 32610
United States, North Carolina
Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27701
Australia, New South Wales
St George Hospital Withdrawn
Kogarah, New South Wales, Australia, 2217
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 1871
Principal Investigator: Dion Forstner         
Calvary Mater Newcastle Recruiting
Newcastle, New South Wales, Australia, 2298
Principal Investigator: Chris Wratten         
Royal North Shore Hospital Recruiting
St Leonards, New South Wales, Australia, 2065
Principal Investigator: Milan Holecek         
Royal Prince Alfred Hospital Recruiting
Sydney, New South Wales, Australia, 2050
Principal Investigator: Chris Milross         
Riverina Cancer Centre Recruiting
Wagga Wagga, New South Wales, Australia, 2650
Principal Investigator: Peter Jeal         
Westmead Hospital Recruiting
Wentworthville, New South Wales, Australia, 2145
Principal Investigator: Michael Veness         
Illawarra Cancer Care Centre Not yet recruiting
Wollongong, New South Wales, Australia, 2500
Australia, Queensland
Princess Alexandra Hospital Recruiting
Brisbane, Queensland, Australia, 4102
Contact: Sandro Porceddu, FRANZCR    +61 7 3240 2111    sandro_porceddu@health.qld.gov.au   
Principal Investigator: Sandro Porceddu         
Royal Brisbane Hospital Recruiting
Herston, Queensland, Australia, 4029
Principal Investigator: Lizbeth Kenny         
Mater QRI Recruiting
South Brisbane, Queensland, Australia, 4101
Principal Investigator: Michael Poulsen         
St Andrew's Toowoomba Hospital Recruiting
Toowoomba, Queensland, Australia, 4350
North Queensland Oncology Service Recruiting
Townsville, Queensland, Australia, 4810
Principal Investigator: Michael Collins         
Premion Recruiting
Tugun, Queensland, Australia, 4224
Principal Investigator: david Christie         
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Principal Investigator: Michael Penniment         
Australia, Victoria
Bendigo Radiotherapy Centre Recruiting
Bendigo, Victoria, Australia
Peter MacCallum Cancer Centre Recruiting
East Melbourne, Victoria, Australia, 3002
Principal Investigator: Margaret Chua         
St Vincents Melbourne Recruiting
Fitzroy, Victoria, Australia
Andrew Love Cancer Care Centre, Geelong Hospital Recruiting
Geelong, Victoria, Australia, 3220
William Buckland Radiotherapy Centre, The Alfred Recruiting
Melbourne, Victoria, Australia, 3004
Principal Investigator: Sidney Davis         
Chile
Clinica Alemana de Santiago Not yet recruiting
Santiago, Chile, 3737
New Zealand
Auckland Hospital Recruiting
Auckland, New Zealand, 1001
Principal Investigator: Andrew Macann         
Christchurch Hospital Recruiting
Christchurch, New Zealand, 4710
Principal Investigator: Ian Ward         
Waikato Hospital Recruiting
Hamilton, New Zealand, 3200
Principal Investigator: Charles de Groot         
Palmerston North Hospital Recruiting
Palmerston North, New Zealand
Principal Investigator: Nick Nedev         
Wellington Hospital Active, not recruiting
Wellington, New Zealand
South Africa
Johannesburg Hospital Not yet recruiting
Johannesburg, South Africa, 2000
Sponsors and Collaborators
Trans-Tasman Radiation Oncology Group (TROG)
Princess Alexandra Hospital, Brisbane, Australia
The Royal Australian and New Zealand College of Radiologists
Investigators
Study Chair: Sandro Porceddu Princess Alexandra Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Trans-Tasman Radiation Oncology Group (TROG)
ClinicalTrials.gov Identifier: NCT00193895     History of Changes
Other Study ID Numbers: TROG 05.01
Study First Received: September 13, 2005
Last Updated: July 31, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Trans-Tasman Radiation Oncology Group (TROG):
Skin cancer
radiotherapy
chemotherapy
surgery

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

ClinicalTrials.gov processed this record on August 28, 2014