E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with relapsed or metastatic squamous cell carcinoma of the head and neck
Previously not treated for relapsed or metastatic SCCHN. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with relapsed or metastatic head and neck and previously not treated for relapsed or metastatic head and neck cancer. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate in patients with relapsed or metastatic squamous cell carcinoma of the head and neck whether progression free survival (PFS) in the arm with cetuximab, paclitaxel and carboplatin based chemotherapy is not markedly worse than PFS in the arm with cetuximab and 5-FU, cisplatin or carboplatin based chemotherapy |
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E.2.2 | Secondary objectives of the trial |
To compare in patients with relapsed or metastatic squamous cell carcinoma of the head and neck the following study variables between both treatment arms:
• Best overall response
• Duration of response
• Time to treatment failure
• Overall survival
• Safety
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
> 18 years
Histologically or cytologically confirmed SCCHN, relapsed and/or metastatic
Patient must have a life expectancy of at least 3 months allowing adequate follow-up toxicity evaluation.
At least 1 dimensionally measurable lesion either by CT scan or MRI or physical examination. PS WHO 0-1 at study entry
Adequate hematological function defined as WBC ≥3 x 109/litre and platelets ≥100 x 109/litre, ANC > 1.5 x 109/litre and Hb > 100 g/L
Adequate liver function: Bilirubin <1.5 x UNL, ALAT or ASAT <3,0 UNL, alkaline phosphates < 2.5 UNL
Creatinine clearance > 50mL/min when treated with Cisplatin
Written informed consent must be obtained according to the local Ethics committee.
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E.4 | Principal exclusion criteria |
>75 years
Nasopharyngeal ca, and cancer of the paranasal sinuses
Any other condition or therapy which in the investigator’s opinion may pose a risk to the patient or interfere with the study objectives
Pregnant or nursing females or patients of child-bearing potential not using adequate methods of birth-control
Patients with active infections or any other serious underlying medical condition, which would impair the ability of the patients to receive the protocol treatment.
Legal incapacity.
Clinically significant cardiovascular disease, , or history of myocardial infarction in the last 6 months.
Patients with clinically relevant neuropathy
Previously treated for relapsed or metastatic SCCHN except radiotherapy
Previously treated with cetuximab, cisplatin/carboplatin, 5-FU or taxanes for locally advanced SCCHN within 3 months before study entry
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E.5 End points |
E.5.1 | Primary end point(s) |
patients with relapsed or metastatic squamous cell carcinoma of the head and neck whether the PFS rate in the arm with cetuximab combined with carboplatin and paclitaxel based chemotherapy is not markedly worse than PFS in the arm with cetuximab combined with cisplatin and 5-FU based chemotherapy |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Progression free survival is defined as the period from randomization until first observation of PD, or death due to any cause. This will be assessed by MRI or CT at baseline, after cycle 2, 4 and 6 and thereafter every 3rd month during 2 years post randomization and thereafter every 6 month until 3 years post randomization, or progressive disease |
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E.5.2 | Secondary end point(s) |
Best overall response
Duration of response
Time to treatment failure
Overall survival
Safety
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall response, in months will be determined for patients whose best response was either CR or PR
Duration of response, in months will determined for patients whose best response was either CR or PR. It is defined as the time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death. If a patient has not had PD, then the duration of response will be censored on the date of last known tumor assessment.
Time to treatment failure;the time in months from randomization until the date of the first occurrence of one of the events defining treatment failure.
Overall survival;the time from the day of randomization to death from any cause.
Safety and toxicity of the two treatments will be evaluated |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 30 |