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Trial record 1 of 1 for:    NCT01855451
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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. Identifier: NCT01855451
Recruitment Status : Active, not recruiting
First Posted : May 16, 2013
Last Update Posted : November 18, 2022
Information provided by (Responsible Party):
Trans Tasman Radiation Oncology Group

Brief Summary:

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

Detailed Description:

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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 189 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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)
Drug: Cetuximab
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)
Drug: Cisplatin

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. 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).

  2. 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

  3. 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)

  4. Impact on Health Related Quality of Life [ Time Frame: 36 months ]
  5. 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.

  6. 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)

  7. 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)

  8. 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

  9. 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).

  10. 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

  11. Failure-free survival [ Time Frame: 36 months ]
    To compare failure-free survival by clinical and radioloigical assessments

  12. Overall survival [ Time Frame: 60 months ]
    To compare overall survival by clinical assessment.

  13. 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.

  14. Complete response rate [ Time Frame: 20 weeks ]
    To compare FDG-PET-CT complete response rate at week 20

  15. 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.

  16. 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

  17. 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.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 > 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

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:

    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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01855451

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Australia, Australian Capital Territory
Canberra Hospital
Canberra, Australian Capital Territory, Australia
Australia, New South Wales
Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia, 2050
Liverpool Hospital
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 Hospital
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Royal Brisbane and Womens Hospital
Herston, Queensland, Australia, 4006
Townsville Hospital
Townsville, Queensland, Australia, 4810
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
Austin Hospital
Melbourne N., Victoria, Australia, 3084
Australia, Western Australia
Sir Charles Gairdner
Nedlands, Western Australia, Australia, 6009
New Zealand
Auckland City Hospital
Auckland, New Zealand, 1344
Palmerston North Hospital
Palmerston, New Zealand, 4442
Sponsors and Collaborators
Trans Tasman Radiation Oncology Group
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Study Chair: D Rischin, Dr TROG and Peter MacCallum Cancer Centre
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Trans Tasman Radiation Oncology Group Identifier: NCT01855451    
Other Study ID Numbers: TROG 12.01
ACTRN12613000279729 ( Registry Identifier: ANZCTR )
First Posted: May 16, 2013    Key Record Dates
Last Update Posted: November 18, 2022
Last Verified: November 2022
Keywords provided by Trans Tasman Radiation Oncology Group:
Human Papilloma Virus
Squamous Cell
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents
Antineoplastic Agents, Immunological