E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Head and neck cancer of squamous cell origin |
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E.1.1.1 | Medical condition in easily understood language |
Head and neck cancer of squamous cell origin |
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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 | 10071537 |
E.1.2 | Term | Head and neck cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071536 |
E.1.2 | Term | Head and neck cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This is a phase II, open-label, randomized study of MEHD7945A versus cetuximab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck who have progressed during or following platinum-based chemotherapy. The main objective is to evaluate the efficacy of MEHD7945A (administered every 2 weeks) versus cetuximab (administered weekly) in all and in biomarker positive patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), as measured by progression-free survival (PFS). |
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E.2.2 | Secondary objectives of the trial |
• To assess the clinical activity of MEHD7945A versus cetuximab, as measured by objective response rate, disease control rate, duration of objective response, time to disease progression, and overall survival in all patients and in biomarker positive patients
• To evaluate the safety and tolerability of MEHD7945A versus cetuximab
• To characterize the pharmacokinetics of MEHD7945A
• To evaluate the incidence and impact of anti-MEHD7945A antibodies
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Histologically confirmed Stage III or IV R/M SCCHN (according to the American Joint Committee on Cancer) that has progressed on or after platinum based chemotherapy and is not suitable for local therapy
•Progressive disease on or after a first-line platinum-based chemotherapy regimen for R/M SCCHN (maximum of six cycles)
•Availability and willingness to provide archival tumor tissue for biomarker testing
•Age ≥18 years
•Male and female
•No healthy volunteers
•Life expectancy ≥12 weeks
•ECOG 0-2
•Disease that is measurable per RECIST v1.1
•Adequate hematologic and end-organ function
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E.4 | Principal exclusion criteria |
•Nasopharyngeal cancer
•Prior treatment with an investigational or approved agent for the purpose of inhibiting HER family members with the exception of treatment with an EGFR inhibitor as part of definitive therapy for locally advanced disease and if completed/terminated within more than one year before study enrollment
•Last anti tumor therapy within 4 weeks prior to Day 1 of the study treatment
•Major surgical procedure within 4 weeks prior to Day 1 of the study treatment
•Current severe, uncontrolled systemic disease
•History of cardiac heart failure of any New York Heart Association criteria or serious cardiac arrhythmia requiring treatment
•History of myocardial infarction within 6 months prior to Day 1 of the study treatment, or history of unstable angina
•Clinically significant history of liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; or current alcohol abuse
•Clinically significant gastrointestinal bleeding within 6 months prior to Day 1 of the study treatment
•History of ILD
•History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy
•Primary central nervous system (CNS) malignancy or untreated/active CNS metastases
•Women during pregnancy or lactation |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is PFS. PFS is defined as the time from randomization to documented disease progression assessed by the investigator or death on study, whichever occurs first. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Data for each patient without documented disease progression or death on study will be censored at the time of his or her last tumor assessment. If no tumor assessments were performed after the baseline visit, the data will be censored at the time of randomization plus 1 day. Death on study is defined as death
from any cause within 30 days of the last dose of study treatment. |
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E.5.2 | Secondary end point(s) |
•Objective response, disease control, duration of objective response, time to disease progression, and overall survival
•Incidence, nature, and severity of adverse events, graded according to the NCI CTCAE v4.0
•Clinically significant changes in vital signs, physical findings, and clinical laboratory results during and following administration of study treatment
•MEHD7945A minimum and maximum serum concentration prior to infusion on Day 1 of Cycles 1 through 4 and at study completion (only Cmin at study completion)
•Serum anti-therapy antibodies (ATAs) to MEHD7945A prior to infusion on Day 1 of Cycles 1 and 4 and at study completion
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Objective response is defined as a complete or partial response according to RECIST v1.1; objective responses must be confirmed ≥4 weeks after the initial response.
- for other timepoints: as stated above in E.5.2 |
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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 | Yes |
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 | 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 | Yes |
E.8.1.6 | Cross over | Yes |
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.8.2.4 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 | Yes |
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 |
Australia |
Belgium |
Bulgaria |
France |
Germany |
Hungary |
Italy |
Romania |
Spain |
United Kingdom |
United States |
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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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Study closure is expected to occur either 12 months after the last patient is enrolled in the study or when all patients in the study have died, whichever
occurs first. |
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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 | 3 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |