E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent/metastatic squamous cell cancer of the head and neck |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 evaluate progression-free survival time of subjects treated with EMD 1201081 + cetuximab compared to cetuximab alone in etuximab-naïve subjects with recurrent and/or metastatic SCCHN who have progressed on a cytotoxic therapy. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the overall response (by RECIST 1.0) or disease control status (CR + PR + SD) of subjects treated with EMD 1201081 + cetuximab compared to cetuximab alone in subjects with R/M SCCHN.
• To evaluate overall survival time in subjects treated with EMD 1201081 + cetuximab as second-line treatment.
• To study the safety and tolerability of the combination EMD 1201081 + cetuximab in the overall trial population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated written informed consent prior to any trial-specific procedure.
2. Male or female, age ≥ 18 years.
3. Histologically confirmed squamous cell carcinoma of the head and neck that is recurrent and/or metastatic; documented in the medical record.
4. History of progressing disease on a first-line cytotoxic chemotherapy regimen such as 5-FU + cisplatin, taxanes, etc. for their R/M SCCHN. (A history of chemotherapy/ radiation therapy for localized disease does not count as a first-line regimen.)
5. The subject is suited for systemic therapy in the opinion of the Investigator.
6. At least one radiographically documented lesion assessable according to RECIST 1.0. Lesions in previously irradiated areas should be measurable (i.e. the lesion must be adequately measurable in at least one dimension; longest diameter to be recorded as ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan). If the sole site of measurable disease is in a prior radiation field, there must be unequivocal evidence of progression at ≥ 8 weeks since the completion of radiation or a positive biopsy.
7. ECOG performance status of 0 or 1.
8. If female, either post-menopausal, surgically sterile, or having a negative urine or serum pregnancy test (β-HCG) at screening and practicing medically accepted contraception. If male, practicing contraception if risk of conception exists. For relevant subjects, the duration of contraception should be 1 week prior to the start of therapy for females through receipt of trial therapy and at the start of trial therapy through 4 weeks after receipt of trial therapy for males.
9. Recovered from previous toxicities of prior cytotoxic regimen to CTCAE Grade 1 (with the exception of alopecia).
10. Hemoglobin ≥ 9 g/dL (without transfusion support, no transfusion within 7 days of screening).
11. Neutrophils ≥ 1.5 x 109/L.
12. Platelets ≥ 100 x 109/L.
13. PT/PTT ≤ 1.5 times the upper limit of normal for the site, unless there is therapeutic anti-coagulation (see bellow; INR values should be converted to PT for screening).
14. Serum creatinine ≤ 1.5 times the upper limit of normal for the site.
15. ALT and AST ≤ 3 times the upper limit of normal for the site.
16. Be willing and able to comply with the protocol procedures for the duration of the trial. |
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E.4 | Principal exclusion criteria |
1. History of prior exposure to cetuximab or panitumumab or any other approved or investigational anti-EGFR agents.
2. Undifferentiated nasopharyngeal carcinoma.
3. Chemotherapy, radiotherapy or any investigational agents within 4 weeks of first dose of trial medication.
4. Major surgical or planned procedure within 30 days prior to first dose of trial medication (isolated biopsies are not counted as major surgical procedures).
5. Other active malignancy besides non-metastatic basal cell or squamous cell carcinoma of the skin or second primary squamous cell carcinoma of the head and neck.
6. Impaired cardiac function (e.g. left ventricular ejection fraction < 45% defined by echocardiograph or other study), history of uncontrolled serious arrhythmia, unstable angina pectoris, congestive heart failure NYHA III and IV), myocardial infarction within the last 12 months prior to trial entry, signs of pericardial effusion.
7. Hypertension uncontrolled by standard pharmacologic therapies.
8. History of diagnosed interstitial lung disease.
9. Patient requires systemic anti-coagulation (e.g. warfarin > 10mg/day
10.Pregnancy or breast feeding.
11. Legal incapacity or limited legal capacity.
12. Significant medical or psychiatric disease which makes the trial inappropriate for the subject in the Investigator’s opinion.
13. Any brain metastasis and/or leptomeningeal disease (known or suspected).
14. Significant pre-existing immune deficiency such as infection by HIV (documented or known).
15. Clinically significant ongoing infection.
16. Known hypersensitivity to the trial treatments.
17. Participation in another clinical trial within the past 30 days.
18. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
19. Other significant disease that in the Investigator’s opinion would exclude the subject from the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) time |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker, Immunogenecity |
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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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end of the trial is defined as 1 year after the last subject has had his/her End-of-Study Visit. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |