RecruitingPhase 3ACTRN12613000279729

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

Sponsor

Trans-Tasman Radiation Oncology Group

Enrollment

200 participants

Start Date

Jun 17, 2013

Study Type

Interventional

Conditions

HPV positive Oropharyngeal Squamous Cell Carcinoma (OPSCC)

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.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria17

Aged 18 years or older
Has provided written Informed Consent for participation in this trial
Histologically confirmed squamous cell carcinoma of the oropharynx with p16 positive status confirmed locally by immunohistochemistry
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.
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.
No prior treatment for oropharyngeal cancer
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
ECOG performance status score of 0-1
Participants capable of childbearing are using adequate contraception and intend to continue use of contraception for at least 6 months following completion of treatment
Negative pregnancy test within 72 hours prior to randomisation of women who are of childbearing potential
Suitable for follow-up for at least 24 months as per trial protocol.
Sufficient proficiency in English, cognitive capacity and willingness to complete questionnaires

Exclusion Criteria17

History of unknown primary of the head and neck
T4, N3 or distant metastases
Smoking history >10 pack years with N2b or c nodal status
Women who are pregnant or lactating.
Previous radiotherapy to the area to be treated (excluding superficial radiotherapy for a cutaneous malignancy)
Previous cisplatin or carboplatin chemotherapy
Prior EGFR targeted therapy of any kind
Primary surgery to the affected area (excisional biopsy allowed)
Peripheral neuropathy > /= grade 2 (CTCAE v4.0)
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)
Tinnitus > /= grade 2 (CTCAE v4.0)
History of interstitial lung disease or evidence of interstitial lung disease on pre-registration CT
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
Patients known to be HIV positive
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

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Interventions

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

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)