E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck cancer |
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 assess the efficacy of Sym004 in patients with recurrent and/or metastatic SCCHN who have disease progression during or within 12 weeks after treatment with an anti-EGFR mAb-containing regimen |
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E.2.2 | Secondary objectives of the trial |
• To assess the safety profile of Sym004 • To assess the biological activity in tumor and skin biopsies • To determine overall survival (OS) • To evaluate potential biomarkers • To determine the pharmacokinetic profile of Sym004
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed diagnosis initially or at relapse of SCCHN of the oral cavity, oropharynx, hypopharynx or larynx 2. Recurrent and/or metastatic SCCHN not amenable to curative treatment with surgery and/or (chemo)radiation 3. Previous treatment with a marketed anti-EGFR mAb in the palliative setting either as monotherapy or in combination with chemotherapy or radiotherapy and showing: a. Documented clinical benefit or response for at least 8 weeks (PR, CR or SD verified by CT scan or MRI according to RECIST) on the anti-EGFR mAb-based therapy and b. Documented disease progression (PD verified by CT scan or MRI according to RECIST) during or within 12 weeks following the last administration of anti-EGFR mAb 4. Accessible tumor for biopsy and patient acceptance of repeat tumor biopsies 5. At least one measurable lesion according to RECIST (1.1) at screening* 6. ECOG performance status 0-1 7. Normal organ or bone marrow function as defined below: a. ANC > 1.5 x109/L (1,500/mm3) b. Hemoglobin ≥ 9 g/dl c. Platelet count ≥ 75 x109/L (75,000/mm3) d. Bilirubin < 1.5 x upper normal limit e. Alkaline Phospatase ≤ 2.5 x upper normal limit (unless known bone metastases) f. AST(SGOT)/ALT(SGPT) ≤ 2.5 x upper normal limit (unless known liver metastases) g. Serum creatinine ≤1.5 x upper normal limit or creatinine clearance > 50 ml/min calculated according to Cockroft-Gault h. S-Na, S-K, S-Mg and S-Ca CTCAE < grade 3 for both low and high values 8. Age ≥18 years 9. Following receipt of verbal and written information about the trial, the patient must provide signed informed consent before any trial related activity is carried out * Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion. |
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E.4 | Principal exclusion criteria |
1. More than 2 lines of prior chemotherapy in the palliative setting 2. Expected survival <12 weeks 3. Patients with known brain metastases 4. Chemotherapy or radiation therapy within 21 days prior to Visit 2 at the exception of palliative radiotherapy for bleeding or pain, which is allowed anytime, if not given on target lesions 5. Anti-EGFR mAbs within 14 days prior to Visit 2 6. Patients with known previous grade > 3 infusion related reactions with chimeric monoclonal antibodies 7. History of other malignancy within 5 years prior to Visit 2, with the exception of basal cell carcinoma of the skin and carcinoma in situ of the cervix or urinary bladder 8. Severe infection requiring iv treatment 9. Any other concurrent uncontrolled disease or medical conditions that are deemed to interfere with the conduct of the trial as judged by the investigator 10. Major surgery within 4 weeks prior to Visit 2 and patients must have recovered from effects of major surgery 11. Known HIV positive 12. Known active hepatitis B or C 13. Patients with known allergy to the components in the study drug 14. Clinically significant and uncontrolled cardiac disease including unstable angina, acute myocardial infarction within six months prior to Visit 2, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities and controlled and well treated chronic atrial fibrillation 15. Current participation in any other interventional clinical trial 16. Patients known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 17. Male patients not willing to use adequate contraception or female of childbearing potential not willing to use an effective form of contraception such as hormonal birth control, intrauterine device or double barrier method during treatment with Sym004 and at least 3 months thereafter 18. Breast feeding women or women with a positive pregnancy test at Visit 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of Progression Free Survival (PFS) at 24 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Adverse events • Objective tumor response (according to RECIST (1.1)) • Time to progression (TTP) • Overall survival (OS) • Skin rash (CTCAE grading (v. 4.02), duration) • Biomarkers (e.g. Circulating Tumor Cells, HPV, mutation of EGFR-vIII, KRAS, HRAS, NRAS, BRAF, PIK3CA, PTEN, Her2, Her3, c-Met) • Pharmacokinetic profile (AUC, CL, Cmax, Cmin, T1/2) • Host immune response: Antidrug antibody (ADA)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinical assessment takes place on an ongoing basis during the study |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.2 | Open | No |
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 | 1 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | No |
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
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The last visit of the last subject undergoing the trial |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |