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TROG12.01 A Randomised Trial of Weekly Cetuximab and Radiation Versus Weekly Cisplatin and Radiation in Good Prognosis Locoregionally Advanced HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Phase 3
18 Years
Not Enrolling
HPV Positive Oropharyngeal Squamous Cell Carcinoma

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Trial Information

TROG12.01 A Randomised Trial of Weekly Cetuximab and Radiation Versus Weekly Cisplatin and Radiation in Good Prognosis Locoregionally Advanced HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is
increasing in incidence and has an improved prognosis compared to other head and neck
malignancies when treated with standard combination chemoradiation.

The current standard regimen of high dose cisplatin and Radiation Therapy (RT) for head and
neck cancer patients results in significant toxicity and is at the limits of tolerance. The
excellent prognosis of patients with HPV-positive OPSCC raises concerns about overtreatment
with the current standard of care, resulting in unnecessary acute and late morbidity.

Therefore, investigation of chemo-sparing or chemo-modified regimens with RT for
HPV-associated OPSCC that do not compromise efficacy is warranted. A number of regimens less
intensive than high dose cisplatin are being used in clinical practice for patients with
good prognosis HPV OPSCC, but no comparative trials have been performed in this population.
The trial population will be restricted to low risk HPV-associated OPSCC.

Trial Arms:

A- RT (70 Gy in 35 fractions, 5 days a week over 7 weeks) with weekly Cetuximab (400 mg/m2
loading dose IV prior to radiation, followed by weekly cetuximab 250 mg/m2 for the duration
of the radiotherapy) B- RT(70 Gy in 35 fractions, 5 days a week over 7 weeks) with weekly
Cisplatin (40 mg/m2 IV for the duration of the radiotherapy)

Hypothesis: In patients with locally advanced HPV-associated OPSCC, those treated with
weekly cetuximab and conventionally fractionated radiotherapy will experience less acute
symptom severity than patients receiving weekly cisplatin and conventionally fractionated

Patients will be followed 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. Follow-up for the trial will cease when the last patient
accrued has a minimum of 2 years follow-up i.e. has attended the 24 months post-treatment

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,

1. Absolute neutrophil count (ANC, segs + bands) > /= 1.5 x 109/L

2. Platelet count > /= 100 x 109/L

3. Total bilirubin < /= 1.5 x upper normal limit

4. ALT < /= 2.5 x upper normal limit

5. Calculated creatinine clearance (Cockcroft-Gault formula) or isotopic GFR >

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

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

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:

1. 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

2. 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Symptom Severity

Outcome Description:

The area under curve of symptom severity between weekly cisplatin and Radiotherapy Therapy (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).

Outcome Time Frame:

20 weeks

Safety Issue:


Principal Investigator

D Rischin, Dr

Investigator Role:

Study Chair

Investigator Affiliation:

TROG and Peter MacCallum Cancer Centre


Australia: Department of Health and Ageing Therapeutic Goods Administration

Study ID:

TROG 12.01



Start Date:

May 2013

Completion Date:

May 2019

Related Keywords:

  • HPV Positive Oropharyngeal Squamous Cell Carcinoma
  • Human Papilloma Virus
  • HPV
  • Oropharyngeal
  • Squamous Cell
  • Carcinoma
  • Carcinoma
  • Carcinoma, Squamous Cell