Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000279729
Ethics application status
Approved
Date submitted
6/03/2013
Date registered
8/03/2013
Date last updated
26/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
TROG 12.01 A Randomised Trial of Weekly Cetuximab and Radiation versus Weekly Cisplatin and Radiation in Good Prognosis Locoregionally Advanced HPV-Associated Oropharyngeal Squamous Cell Carcinoma
Scientific title
TROG 12.01 A Randomised Trial of Weekly Cetuximab and Radiation versus Weekly Cisplatin and Radiation in Good Prognosis Locoregionally Advanced HPV-Associated Oropharyngeal Squamous Cell Carcinoma
Secondary ID [1] 281562 0
Nil
Universal Trial Number (UTN)
Trial acronym
HPV Oropharynx
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HPV positive Oropharyngeal Squamous Cell Carcinoma (OPSCC) 287845 0
Condition category
Condition code
Cancer 288193 288193 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Radiation Treatment: 70 Gy in 35 fractions, 5 days a week over 7 weeks.
Systemic Treatment: Weekly Cetuximab (400 mg/m2 loading dose IV prior to radiation, followed by weekly cetuximab 250 mg/m2 for the duration of the radiotherapy)
Intervention code [1] 286083 0
Treatment: Drugs
Intervention code [2] 286305 0
Treatment: Other
Comparator / control treatment
Radiation Treatment: 70 Gy in 35 fractions, 5 days a week over 7 weeks.
Systemic Treatment: Weekly Cisplatin (40 mg/m2 IV for the duration of the radiotherapy)
Control group
Active

Outcomes
Primary outcome [1] 288392 0
To compare the area under curve of symptom severity between weekly cisplatin and RT versus weekly cetuximab and RT from baseline to week 20 (13 weeks post-completion of radiotherapy) as measured by M.D. Anderson Symptom Inventory - Head and Neck Module (MDASI-HN).
Timepoint [1] 288392 0
MDASI-HN; baseline, treatment weeks 1-7, 1, 3, 5, 9 and 13 weeks post treatment.
Secondary outcome [1] 300022 0
To compare other MDASI-HN endpoints: Symptom Interference Score, Modified MDASI-HN Symptom Score, MDASI-HN Symptom Clusters and individual item scores at individual time points.
Timepoint [1] 300022 0
baseline, treatment weeks 1-7, post radiation weeks 1, 3, 5, 9 and 13 as well as 6mths, 12mths and 24mths post treatment.
Secondary outcome [2] 300023 0
To compare health-related quality of life as measured by Functional Assessment of Cancer Therapy – Head and Neck (FACT-HN)
Timepoint [2] 300023 0
Baseline, post RT 9wks, 6mths, 12mths, 24mths and 36mths.
Secondary outcome [3] 300024 0
To compare speech and dietary function as measured by the Performance Status Scale for Head & Neck Cancer Patients (PSS-HN)
Timepoint [3] 300024 0
baseline, post RT 13wks, 6mths, 12mths, 24mths and 36mths.
Secondary outcome [4] 300025 0
To compare clinician-assessed acute and late toxicity using toxicity grading (CTCAE v4.0) reported as worst toxicity and as overall acute toxicity burden (T-score).
Timepoint [4] 300025 0
Each visit (baseline to 60 months post radiation)
Secondary outcome [5] 300026 0
To compare unacceptable locoregional treatment outcome (ULTO) defined as either locoregional failure or specific severe late treatment-related locoregional toxicities.
Timepoint [5] 300026 0
Clinical Examinations; each visit baseline to 60 months post treatment.
Secondary outcome [6] 300027 0
To compare rate of enteral feeding at 12months from end of RT.
Timepoint [6] 300027 0
12mnths post RT.
Secondary outcome [7] 300028 0
To compare functional swallowing outcome measured by swallowing video fluoroscopy.
Timepoint [7] 300028 0
Baseline, 12mths and 24mths post RT.
Secondary outcome [8] 300029 0
To compare hearing impairment as measured by audiometry
Timepoint [8] 300029 0
baseline and 12months post RT.
Secondary outcome [9] 300030 0
To compare hearing impact on health related quality of life (HRQOL) as measured by total score of Hearing Handicap Inventory for Adult Screenign version (HHIA-S)
Timepoint [9] 300030 0
baseline, treatment wk7 and post RT 1 wk, 13 wks, 6mths, 12mths and 24mths.
Secondary outcome [10] 300031 0
To compare depression and anxiety, as measured by depression and anxiety scales of HADS.
Timepoint [10] 300031 0
Baseline, treatment wk 7 and post RT 1wk, 5wks, 13wks, 6mths, 12mths and 24mths.
Secondary outcome [11] 300032 0
To compare overall survival, defined as time from randomisation to death.
Timepoint [11] 300032 0
Clinical Examinations; each visit baseline to 60 months post treatment
Secondary outcome [12] 300033 0
To compare failure-free survival, defined as time from randomisation to failure (locoregional or distant) or death.
Timepoint [12] 300033 0
Clinical Examinations; each visit baseline to 60 months post treatment.

Radiological examinations; baseline and post RT 13 wks, 6 mths, 12 mths, 24 mths, 36mths and any time of clinically indicated.
Secondary outcome [13] 300034 0
To compare time to locoregional failure defined as time from randomisation to locoregional failure.
Timepoint [13] 300034 0
Clinical Examinations; each visit baseline to 60 months post treatment.

Radiological examinations; baseline and post RT 13 wks, 6 mths, 12 mths, 24 mths, 36mths and any time of clinically indicated.
Secondary outcome [14] 300035 0
To compare FDG-PET or FDG-PET-CT complete response rate at 13 weeks post RT.
Timepoint [14] 300035 0
Baseline and 13 weeks post-completion Raditaiton therapy
Secondary outcome [15] 300036 0
To compare the pattern of disease failure (locoregional [recurrence at primary tumour site and/or regional nodes], distant, both).
Timepoint [15] 300036 0
Radiological examinations; baseline and post RT 13 wks, 6mths, 12mths, 24mths, 36mths and any time of clinically indicated.
Secondary outcome [16] 300037 0
To compare quality adjusted life years (QALYS) using the EQ-5D-5L.
Timepoint [16] 300037 0
Baseline and post treatment (13 weeks, 6 months, 12 months, 24months and 36 months)
Secondary outcome [17] 300102 0
To compare work status and time to return to work questionnaire
Timepoint [17] 300102 0
Baseline, treatment wk7 and post RT 1wk, 13wks, 6mths, 12mths, 24mths and 36mnths.
Secondary outcome [18] 301470 0
To compare cost of health resource utilisation by
comparing the cost of administrating each arm in addtion to the treatment of toxcicites (e.g. need for feed tube insertion, hopsitalisations, salvage surgery, supportive care medicines)
Timepoint [18] 301470 0
End of Study

Eligibility
Key inclusion criteria
1. Aged 18 years or older
2. Has provided written Informed Consent for participation in this trial
3. Histologically confirmed squamous cell carcinoma of the oropharynx with p16 positive status confirmed locally by immunohistochemistry
4. Stage III (excluding T1-2N1) or stage IV (excluding T4, N3, and distant metastasis) if smoking history of < /=10 pack years. If > 10 pack years nodal disease must be N0 – N2a.
5. If an excisional biopsy has been performed, patients remain eligible for the study provided there is clinically measurable disease prior to commencing RT. The residual disease should still meet the stage criteria required for the trial e.g. excisional biopsy of a node with residual T3 primary, or tonsillectomy for T1 primary with residual > N2a nodes.
6. No prior treatment for oropharyngeal cancer
7. Adequate haematological, renal, and hepatic function as defined by,
a) Absolute neutrophil count (ANC, segs + bands) > /= 1.5 x 109/L
b) Platelet count > /= 100 x 109/L
c) Total bilirubin < /= 1.5 x upper normal limit
d) ALT < /= 2.5 x upper normal limit
e) Calculated creatinine clearance (Cockcroft-Gault formula) or isotopic GFR > 55ml/min
8. ECOG performance status score of 0-1
9. Participants capable of childbearing are using adequate contraception and intend to continue use of contraception for at least 6 months following completion of treatment
10. Negative pregnancy test within 72 hours prior to randomisation of women who are of childbearing potential
11. Suitable for follow-up for at least 24 months as per trial protocol.
12. Sufficient proficiency in English, cognitive capacity and willingness to complete questionnaires
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of unknown primary of the head and neck
2. T4, N3 or distant metastases
3. Smoking history >10 pack years with N2b or c nodal status
4. Women who are pregnant or lactating.
5. Previous radiotherapy to the area to be treated (excluding superficial radiotherapy for a cutaneous malignancy)
6. Previous cisplatin or carboplatin chemotherapy
7. Prior EGFR targeted therapy of any kind
8. Primary surgery to the affected area (excisional biopsy allowed)
9. Peripheral neuropathy > /= grade 2 (CTCAE v4.0)
10. Sensori-neural hearing impairment >= grade 2 (CTCAE v4.0, hearing impaired, not enrolled on a monitoring program) which may be exacerbated by cisplatin (Audiometric abnormalities without corresponding clinical deafness will not be grounds for exclusion)
11. Tinnitus > /= grade 2 (CTCAE v4.0)
12. History of interstitial lung disease or evidence of interstitial lung disease on pre-registration CT
13. History of myocardial infarction within 12 months prior to study entry, uncontrolled congestive heart failure, unstable angina, active cardiomyopathy, unstable arrhythmia, uncontrolled psychotic disorders, active serious infections, active peptic ulcer disease, immunosuppression due to post-organ transplantation or use of immunosuppressants for autoimmune disorders
14. Patients known to be HIV positive
15. Other cancer that was diagnosed:
a) more than 5 years prior to current diagnosis with (i) subsequent evidence of disease recurrence or (ii) clinical expectation of recurrence is greater than 10% or
b) within 5 years of the current diagnosis, with the exception of successfully treated basal cell or squamous cell skin carcinoma, in situ melanoma, or carcinoma in situ of the cervix

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/05/2013
Actual
17/06/2013
Date of last participant enrolment
Anticipated
1/06/2018
Actual
Date of last data collection
Anticipated
30/06/2023
Actual
Sample size
Target
200
Accrual to date
169
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 697 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 698 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [3] 699 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [4] 700 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [5] 2770 0
The Canberra Hospital - Garran
Recruitment hospital [6] 2771 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 2772 0
Riverina Cancer Care Centre - Wagga Wagga
Recruitment hospital [8] 2773 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [9] 2774 0
Westmead Hospital - Westmead
Recruitment hospital [10] 2775 0
The Townsville Hospital - Douglas
Recruitment hospital [11] 3469 0
St George Hospital - Kogarah
Recruitment hospital [12] 3470 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [13] 3471 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [14] 3472 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [15] 5116 0
Gold Coast Hospital - Southport
Recruitment outside Australia
Country [1] 4687 0
New Zealand
State/province [1] 4687 0
Auckland
Country [2] 7078 0
New Zealand
State/province [2] 7078 0
Palmerston North

Funding & Sponsors
Funding source category [1] 286369 0
Government body
Name [1] 286369 0
National Health and Medical Research Council (NHMRC)
Country [1] 286369 0
Australia
Funding source category [2] 286860 0
Commercial sector/Industry
Name [2] 286860 0
Merck Serono Australia
Country [2] 286860 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Trans-Tasman Radiation Oncology Group
Address
TROG Central Office
PO Box 88
Waratah NSW 2298
Country
Australia
Secondary sponsor category [1] 285148 0
None
Name [1] 285148 0
Address [1] 285148 0
Country [1] 285148 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288444 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 288444 0
Peter MacCallum Cancer Centre Ethics Committee Peter MacCullum Cancer Centre Locked Bag 1 A'Beckett Street MELBOURNE VIC 8006
Ethics committee country [1] 288444 0
Australia
Date submitted for ethics approval [1] 288444 0
08/02/2013
Approval date [1] 288444 0
28/03/2013
Ethics approval number [1] 288444 0
HREC/13/PMCC/6

Summary
Brief summary
This study aims to compare radiation treatment combined with either cetuximab or cisplatin in patients with locoregionally advanced HPV positive oropharyngeal squamous cell carcinoma (OPSCC) (located at the base of tongue or tonsil)

Who is it for?
You may be eligible to join this study if you are aged 18 years or more, and have been diagnosed with locoregionally advanced HPV positive oropharyngeal squamous cell carcinoma (OPSCC). You should not have received any prior treatment for this cancer.

Trial details;
Participants in this trial will be randomly (by chance) allocated to one of two groups. Participants in one group will receive radiation treatment 5 days a week over 7 weeks, in conjunction with weekly doses of a drug called cetuximab. This drug is administered intravenously, i.e. directly into the vein.

Participants in the other group will receive radiation treatment 5 days a week over 7 weeks in combination with the chemotherapy drug cisplatin, which is also administered intravenously.

Participants will be assessed weekly during treatment, then at 1, 3, 5, 9, 13 weeks post-treatment and at months 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 42, 48, 54, and 60 post-completion of treatment. Assessments will involve blood tests, questionnaires, clinical examination, hearing tests, swallowing tests, and radiological examination. The main research question being answered is whether those treated with weekly cetuximab and conventionally fractionated radiotherapy will experience less acute symptom severity than patients receiving weekly cisplatin and conventionally fractionated radiotherapy.
Trial website
www.trog.com.au
Trial related presentations / publications
nil
Public notes

Contacts
Principal investigator
Name 34968 0
A/Prof Danny Rischin
Address 34968 0
Peter MacCallum Cancer Centre
Locked Bag No 1,
A’Beckett St,
Melbourne, VIC 8006, Australia.
Country 34968 0
Australia
Phone 34968 0
+61 3 9656 1408
Fax 34968 0
Email 34968 0
[email protected]
Contact person for public queries
Name 18215 0
Ms Anetta Matera
Address 18215 0
Peter MacCallum Cancer Centre
Locked Bag No 1,
A’Beckett St,
Melbourne, VIC 8006, Australia.
Country 18215 0
Australia
Phone 18215 0
+61 3 9656 3661
Fax 18215 0
Email 18215 0
[email protected]
Contact person for scientific queries
Name 9143 0
Ms Anetta Matera
Address 9143 0
Peter MacCallum Cancer Centre
Locked Bag No 1,
A’Beckett St,
Melbourne, VIC 8006, Australia.
Country 9143 0
Australia
Phone 9143 0
+61 3 9656 3661
Fax 9143 0
Email 9143 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



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