Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is ongoing, but not recruiting participants.
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: February 12, 2015
Last verified: February 2015
  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 ]

Enrollment: 321
Study Start Date: April 2005
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2016 (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

Locations
United States, Florida
University of Florida Shands Cancer Centre
Gainesville, Florida, United States, 32610
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27701
Australia, New South Wales
Liverpool Hospital
Liverpool, New South Wales, Australia, 1871
Calvary Mater Newcastle
Newcastle, New South Wales, Australia, 2298
Royal North Shore Hospital
St Leonards, New South Wales, Australia, 2065
Royal Prince Alfred Hospital
Sydney, New South Wales, Australia, 2050
Riverina Cancer Centre
Wagga Wagga, New South Wales, Australia, 2650
Westmead Hospital
Wentworthville, New South Wales, Australia, 2145
Illawarra Cancer Care Centre
Wollongong, New South Wales, Australia, 2500
Australia, Queensland
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4102
Royal Brisbane Hospital
Herston, Queensland, Australia, 4029
Mater QRI
South Brisbane, Queensland, Australia, 4101
St Andrew's Toowoomba Hospital
Toowoomba, Queensland, Australia, 4350
North Queensland Oncology Service
Townsville, Queensland, Australia, 4810
Premion
Tugun, Queensland, Australia, 4224
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Bendigo Radiotherapy Centre
Bendigo, Victoria, Australia
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
St Vincents Melbourne
Fitzroy, Victoria, Australia
Andrew Love Cancer Care Centre, Geelong Hospital
Geelong, Victoria, Australia, 3220
William Buckland Radiotherapy Centre, The Alfred
Melbourne, Victoria, Australia, 3004
Chile
Clinica Alemana de Santiago
Santiago, Chile, 3737
New Zealand
Auckland Hospital
Auckland, New Zealand, 1001
Christchurch Hospital
Christchurch, New Zealand, 4710
Waikato Hospital
Hamilton, New Zealand, 3200
Palmerston North Hospital
Palmerston North, New Zealand
Wellington Hospital
Wellington, New Zealand
South Africa
Johannesburg Hospital
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: February 12, 2015
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:
Head and Neck Neoplasms
Skin Neoplasms
Neoplasms
Neoplasms by Site
Skin Diseases
Carboplatin
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on February 26, 2015