Primary objective: To compare the severe (acute and late) toxicity (Grade 3-5), as assessed by CTCAE Version 4, caused by cetuximab and RT to that caused by cisplatin and RT in patients with HPV+OPSCC.Secondary objectives:- Compare overall number of…
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Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure will be the total number of acute and late severe
or life-threatening (Grade 3-5) toxicity events occurring up to two years after
treatment, and will be compared between both arms.
Secondary outcome
The secondary end points are as follows:
* The number of acute severe (Grade 3-5) toxicities in cetuximab arm compared
to cisplatin arm.
* The number of late severe (Grade 3-5) toxicities in cetuximab arm compared to
cisplatin arm.
* Similar or better global QoL of the Arm B (cetuximab) group
* Similar or better late (2 year) swallowing by overall MDADI score in
cetuximab arm
* Compare EORTC swallowing quality of life domain at 2 years and PEG
utilisation rates at 1 year and 2 years between treatment arms.
* Comparison of incremental cost per quality-adjusted life year gained within
trial and extrapolated over lifetime.
* Report overall survival in two arms.
* Report loco-regional recurrence rates for both arms.
Background summary
Oropharyngeal squamous cell carcinoma (OPSCC) incidence is increasing rapidly
in the developed world. This has been attributed to a rise in Human
Papillomavirus (HPV) infection. HPV+OPSCC is considered a distinct disease
entity, affecting younger patients and has a good prognosis following
treatment. Subsequently, patients can live with the considerable side effects
for several decades.
Radiotherapy and cetuximab (Epidermal Growth Factor Receptor-inhibitor) have
demonstrated similar efficacy to *platin* chemoradiotherapy (current standard
treatment containing platinum-based compounds) in head and neck cancer, but is
potentially less toxic.
Results of this trial will be used to determine the optimum treatment of this
debilitating cancer, with the primary aim of decreasing toxicity and improving
quality of life for HPV+OPSCC patients.
Study objective
Primary objective:
To compare the severe (acute and late) toxicity (Grade 3-5), as assessed by
CTCAE Version 4, caused by cetuximab and RT to that caused by cisplatin and RT
in patients with HPV+OPSCC.
Secondary objectives:
- Compare overall number of events of acute severe toxicity between treatment
arms.
- Compare overall number of events of late severe toxicity between treatment
arms.
- Compare the quality of life outcomes assessed by EORTC QLQ C30 and HN35
between the two treatment arms.
- Compare the effect on swallowing of the two treatment arms (assessed by MDADI
and by PEG or RIG utilisation rate at 1 and 2 years).
- Compare the cost-effectiveness of the two treatment arms (assessed by
EuroQoL-5D).
- Compare overall survival, recurrence and metastasis between the two arms.
Study design
Randomised, international, multi-centre, open label, phase III clinical trial
determining the optimum treatment for patients with HPV+OPSCC.
Intervention
Experimental arm:
Cetuximab: IV 400mg/m2 dose 1 week before start of radiotherapy followed by a
weekly IV infusion of 250mg/m2 X 7 during radiotherapy
Control Arm:
Cisplatin: 3 doses of 100mg/m2 given at days 1, 22 and 43 from start of
radiotherapy
Study burden and risks
The most common side effects of radiotherapy are: pain and soreness of mouth
and throat, redness and sometimes ulcers in the skin of the area being treated,
loss of sense of taste, tiredness, hoarseness if the voice box is being
treated, noisy or difficult breathing, dryness of the mouth, difficulty
swallowing, ulcers in the mouth and dental problems.
The most common side effects of cisplatin chemotherapy are: nausea and
vomiting, hearing loss, tiredness, infection, some loss of hair, constipation,
soreness of mouth, very small risk of death, long-term effects including dry
mouth and swallowing problems.
The most common side effects of cetuximab chemotherapy are: skin rash, nausea
and vomiting, tiredness, infection, difficulty swallowing,
soreness of mouth, very small risk of death, long-term effects including dry
mouth and swallowing problems.
Research Support Services, University House, Kirby Corner Road n.a.
Coventry CV4 8UW
NL
Research Support Services, University House, Kirby Corner Road n.a.
Coventry CV4 8UW
NL
Listed location countries
Age
Inclusion criteria
1. AJCC TNM Stage III-IVa [T3N0-T4N0, and T1N1-T4N3] oropharyngeal SCC tumours
2. Clinical multidisciplinary team decision to treat with primary curative chemoradiotherapy.
3. No previous treatment for the primary tumour, including surgery, neck dissection or tracheostomy [except node biopsies or diagnostic tonsillectomy].
4. Medically fit (ECOG 0, 1 or 2).
5. Adequate cardiovascular, haematological, renal and hepatic function.
6. Age 18 years or over.
7. Written informed consent given.
8. Using adequate contraception [male and female participants]. Must take contraceptive measures during, and for at least six months after treatment.
Exclusion criteria
1. Distant metastasis (i.e. stage IVc disease).
2. TNM Stage T1-2N0 disease.
3. Treated with primary radical surgery to the primary site e.g. resection.
4. Concurrent use of CYP3A4 inducers or inhibitors. [A standard course of
dexamethasone or aprepitant for the prevention of cisplatin-induced nausea and vomiting is
permitted]
5. Serious cardiac illness or other medical conditions precluding the use of cisplatin or cetuximab [no history of clinically significant cardiac disease, serious arrhythmias, or significant conduction abnormalities; no uncontrolled seizure disorder; no active neurologic disease; no neuropathy greater than grade 1; hypersensitivity to cisplatin or severe hypersensitivity to cetuximab; receiving live vaccines; receiving phenytoin in prophylactic use; in dehydrated condition]
6. HPV+ patients who have p16+ tumours who also have N2b, N2c or N3 nodal disease and whose lifetime smoking history is also more than 10 pack years (i.e. have both risk factors).
7. Pregnant or lactating.
8. Previous treatment for any other cancer with cytotoxics, radiotherapy or anti-EGFR therapies.
9. Inadequate renal, haematological or liver functions.
10. Patients with clinically significant hearing impairment.
11. Life expectancy less than three months.
12. Other malignancy within the past three years except basal cell skin cancer or pre-invasive carcinoma of the cervix.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005165-21-NL |
| ISRCTN | ISRCTN33522080 |
| CCMO | NL40537.029.14 |