Weekly Cetuximab/RT Versus Weekly Cisplatin/RT in HPV-Associated Oropharyngeal Squamous Cell Carcinoma (HPVOropharynx)

November 16, 2022 updated by: Trans Tasman Radiation Oncology Group

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
189

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Australian Capital Territory
      • Canberra, Australian Capital Territory, Australia
        • Canberra Hospital
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital
      • St George, New South Wales, Australia, 2217
        • St George Hospital
      • Wagga Wagga, New South Wales, Australia
        • Riverina Cancer Care Centre
      • Waratah, New South Wales, Australia
        • Calvary Mater Newcastle
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • Queensland
      • Herston, Queensland, Australia, 4006
        • Royal Brisbane and Womens Hospital
      • Townsville, Queensland, Australia, 4810
        • Townsville Hospital
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandra Hospital
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Peter MacCallum Cancer Centre
      • Melbourne N., Victoria, Australia, 3084
        • Austin Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner
  • New Zealand
      • Auckland, New Zealand, 1344
        • Auckland City Hospital
      • Palmerston, New Zealand, 4442
        • Palmerston North Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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)
Drug: Cisplatin
Radiation: RT (70 Gy in 35 fractions)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
20 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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).
24 months
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
24 mths
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)
36 months
Impact on Health Related Quality of Life
Time Frame: 36 months
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.
12 months
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)
36 months
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)
60 months
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
12 months
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).
24 months
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
36 months
Failure-free survival
Time Frame: 36 months
To compare failure-free survival by clinical and radioloigical assessments
36 months
Overall survival
Time Frame: 60 months
To compare overall survival by clinical assessment.
60 months
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.
36 months
Complete response rate
Time Frame: 20 weeks
To compare FDG-PET-CT complete response rate at week 20
20 weeks
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.
24 months
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
24 months
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.
60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Trans Tasman Radiation Oncology Group

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: D Rischin, Dr, TROG and Peter MacCallum Cancer Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 3, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 23, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 13, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 16, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 18, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TROG 12.01
  • ACTRN12613000279729 (Registry Identifier: ANZCTR)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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