Weekly Cetuximab/RT Versus Weekly Cisplatin/RT in HPV-Associated Oropharyngeal Squamous Cell Carcinoma (HPVOropharynx)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01855451|
Recruitment Status : Active, not recruiting
First Posted : May 16, 2013
Last Update Posted : February 9, 2021
A standard treatment for patients with head and neck cancer is radiation given with high doses of a chemotherapy drug called cisplatin, given every 3 weeks during the radiation. This treatment is effective but can significantly increase side effects such as difficulty with swallowing, a sore mouth, fatigue, hearing loss, ringing in the ears and kidney failure. In Australia, a commonly used treatment HPV-Associated Oropharyngeal Squamous Cell Carcinoma is a lower dose of cisplatin given weekly during the radiation. The high dose and low dose schedules result in a similar total dose of cisplatin being given during the radiation, but it is thought that the weekly schedule results in fewer side effects while maintaining effectiveness.
Another approach widely used around the world for patients with head and neck cancer, is to administer the antibody, cetuximab, weekly during radiation. Cetuximab has a very different side effect profile to cisplatin, and has been reported to result in less exacerbation of radiation related side effects. Both cetuximab and cisplatin can reduce the growth of a cancer and increase the effectiveness of radiation. Both cisplatin and cetuximab appear to be effective treatments in combination with radiation, but have not been directly compared.
The purpose of this study is to compare the treatment related side effects (both acute and longer term) between the cisplatin and cetuximab regimens. Both treatments would be given with the same dose of radiation therapy over 7 weeks. The results of this trial will help determine the optimal treatment for patients with HPV-Associated Oropharyngeal Squamous Cell Carcinoma.
|Condition or disease||Intervention/treatment||Phase|
|HPV Positive Oropharyngeal Squamous Cell Carcinoma||Drug: Cetuximab Radiation: RT (70 Gy in 35 fractions) Drug: Cisplatin||Phase 3|
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.
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 radiotherapy.
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 review.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||189 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||June 3, 2013|
|Actual Primary Completion Date :||April 30, 2020|
|Estimated Study Completion Date :||August 23, 2023|
Active Comparator: Radiation Therapy + Cetuximab
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)
Radiation: RT (70 Gy in 35 fractions)
Active Comparator: Radiation Therapy + Cisplatin
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)
Radiation: RT (70 Gy in 35 fractions)
- Symptom Severity [ Time Frame: 20 weeks ]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).
- Symptom severity [ Time Frame: 24 months ]Symptom severity measured by MDASI-HN (Symptom Interference Score, Symptom Score, Symptom Clusters and individual item scores at individual time points)and by Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN).
- Interference of symptoms with daily life [ Time Frame: 24 mths ]To compare interference of symptoms with daily life using the MDASI-HN Symptom Interference Score and Quality adjusted life years (QALYs) using the EQ-5D-5L
- Psychological distress [ Time Frame: 36 months ]To compare psychological distress measured by FACT-HN domain scores and depression and anxiety scales of Hospital Anxiety and Depression Scale (HADS)
- Impact on Health Related Quality of Life [ Time Frame: 36 months ]
- Swallowing dysfunction [ Time Frame: 12 months ]To compare swallowing dysfunction by Functional swallowing outcome (video fluoroscopy), CTCAE (v4.0) dysphagia, MDASI and FACT questionnaires, enteral feeding rates.
- Speech and dietary function [ Time Frame: 36 months ]To compare speech and dietary function as measured by the Performance Status Scale for Head & Neck Cancer Patients (PSS-HN)
- Clinician-assessed acute and late toxicity [ Time Frame: 60 months ]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)
- Rate of enteral feeding [ Time Frame: 12 months ]To compare rate of enteral feeding at 12 months following treatment using Barnard's exact test for the comparison of two proportions
- Hearing impairment [ Time Frame: 24 months ]To compare hearing impairment, as measured by total score of the Hearing Handicap Inventory for adults, screening version (HHIA-S) and audiometry (results will be evaluated according to CTCAE 3 and 4 criteria, Brock criteria, Chang criteria and SIOP Boston Ototoxicity Scale).
- Time to locoregional failure [ Time Frame: 36 months ]To compare time to locoregional failure primarily determined by evidence of progression or recurrence clinically or radiologically
- Failure-free survival [ Time Frame: 36 months ]To compare failure-free survival by clinical and radioloigical assessments
- Overall survival [ Time Frame: 60 months ]To compare overall survival by clinical assessment.
- Pattern of disease failure [ Time Frame: 36 months ]Pattern of disease failure (locoregional [recurrence at primary tumour site and/or regional nodes], distant, both) as assessed radiologically.
- Complete response rate [ Time Frame: 20 weeks ]To compare FDG-PET-CT complete response rate at week 20
- Cost of health resource utilisation [ Time Frame: 24 months ]To compare cost of health resource utilisation via questionnaires EQ-5D-5L and RTOG return to work questionnaire.
- Work status and time to return to work [ Time Frame: 24 months ]To compare work status and time to return to work by RTOG questionnaire
- Potential prognostic markers [ Time Frame: 60 months ]To correlate several potential prognostic markers (including but not limited to EGFR protein level, EGFR copy number, ERCC1, plasma hepatocyte growth factor level, and plasma IL-8) with failure-free survival, overall survival and time to locoregional failure.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01855451
|Australia, Australian Capital Territory|
|Canberra, Australian Capital Territory, Australia|
|Australia, New South Wales|
|Chris O'Brien Lifehouse|
|Camperdown, New South Wales, Australia, 2050|
|Liverpool, New South Wales, Australia, 2170|
|St George Hospital|
|St George, New South Wales, Australia, 2217|
|Riverina Cancer Care Centre|
|Wagga Wagga, New South Wales, Australia|
|Calvary Mater Newcastle|
|Waratah, New South Wales, Australia|
|Westmead, New South Wales, Australia, 2145|
|Royal Brisbane and Womens Hospital|
|Herston, Queensland, Australia, 4006|
|Townsville, Queensland, Australia, 4810|
|Princess Alexandra Hospital|
|Woolloongabba, Queensland, Australia, 4102|
|Australia, South Australia|
|Flinders Medical Centre|
|Bedford Park, South Australia, Australia, 5042|
|Peter MacCallum Cancer Centre|
|East Melbourne, Victoria, Australia, 3002|
|Melbourne N., Victoria, Australia, 3084|
|Australia, Western Australia|
|Sir Charles Gairdner|
|Nedlands, Western Australia, Australia, 6009|
|Auckland City Hospital|
|Auckland, New Zealand, 1344|
|Palmerston North Hospital|
|Palmerston, New Zealand, 4442|
|Study Chair:||D Rischin, Dr||TROG and Peter MacCallum Cancer Centre|