E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
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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 whether panitumumab plus chemotherapy improves overall survival (OS) compared to chemotherapy alone as first line treatment for metastatic and/or recurrent squamous cell carcinoma of the head and neck (SCCHN). |
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E.2.2 | Secondary objectives of the trial |
To evaluate progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), time to progression (TTP), and safety. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically or cytologically confirmed SCCHN or its variants (eg, basaloid squamous cell carcinoma and adenosquamous cell carcinoma) of the oral cavity, oropharynx, hypopharynx, or larynx • Diagnosis of metastatic disease and/or recurrent disease following locoregional therapy and determined to be incurable by surgery or radiotherapy • Subjects who have received radiation as primary therapy are eligible if locoregional recurrence is in the field of radiation and has occurred (greater than or equal to) 6 months after the completion of radiation therapy. Subjects whose locoregional recurrence is solely outside the field of radiation are eligible if the recurrence has occurred (greater than or equal to) 3 months after the completion of radiation therapy. • Measurable or non-measurable disease. Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to randomization. • ECOG performance status of 0 or 1 • Man or woman (greater than or equal to) 18 years of age • Hematological function, as follows ((less than or equal to) 10 days prior to randomization): • Absolute neutrophil count (ANC) (greater than or equal to) 1.5 x 109/L • Platelet count (greater than or equal to) 100 x 109/L • Hemoglobin (greater than or equal to) 9 g/dL • Renal function, as follows ((less than or equal to) 10 days prior to randomization): • Creatinine clearance (CrCl) (greater than or equal to) 50 mL/min calculated by the Cockcroft-Gault method as follows: • Male creatinine clearance = (140 - age) x (weight in Kg) / (serum Cr x 72) • Female creatinine clearance = (140 - age) x (weight in Kg) x 0.85 / (serum Cr x 72) • Hepatic function, as follows ((less than or equal to) 10 days prior to randomization): • Aspartate aminotransferase (AST) (less than or equal to) 3 x upper limit of normal (ULN) ((less than or equal to) 5 X ULN if liver metastases) • Alanine aminotransferase (ALT) (less than or equal to) 3 x ULN ((less than or equal to) 5 X ULN if liver metastases) • Total bilirubin (less than or equal to) 1.5 X ULN • Electrolytes, as follows ((less than or equal to) 10 days prior to randomization): • Magnesium (greater than or equal to) lower limit of normal (LLN) • Negative pregnancy test (less than or equal to) 72 hours prior to randomization (females of child bearing potential only) • Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1). |
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E.4 | Principal exclusion criteria |
• Documented or symptomatic central nervous system metastases • History of another primary cancer, except: • Curatively treated in situ cervical cancer, or • Curatively resected non-melanoma skin cancer, or • Other primary solid tumor curatively treated with no known active disease present and no treatment administered for (greater than or equal to) 2 years prior to randomization • Subjects whose only site of metastatic disease is a single spiculated lung nodule are assumed to have a second lung primary and are excluded unless there is unequivocal pathological confirmation of metastasis of the SCCHN primary • Nasopharyngeal carcinoma • Prior systemic treatment for metastatic and/or recurrent SCCHN • Subjects with recurrent disease may have received re-irradiation; however subjects who received chemotherapy concomitantly with re-irradiation are excluded. • Prior systemic chemotherapy for SCCHN as part of the initial multimodality treatment for locally advanced disease if completed (less than) 6 months prior to randomization • Prior cisplatin-containing induction chemotherapy followed by cisplatin-containing chemoradiotherapy • Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, etuximab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib) • Subjects requiring immunosuppressive agents (eg, methotrexate and cyclosporine), however corticosteroids are allowed • Known allergy or hypersensitivity to any component of the study drugs • Major surgery requiring general anesthesia and a significant incision (ie, larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy) (less than or equal to) 28 days or minor surgery (excluding central venous catheter placement, percutaneous feeding tube, and biopsy) (less than or equal to) 14 days prior to randomization. Subjects must have recovered from surgery related toxicities. • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) (less than or equal to) 1 year prior to randomization • History of interstitial lung disease eg, pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan • Symptomatic peripheral neuropathy grade (greater than or equal to) 2 based on the CTCAE v3.0 • Grade (greater than or equal to) 3 hearing loss based on the CTCAE v3.0 Auditory/Ear (Hearing [without monitoring program]) • Subjects not recovered from all previous acute radiotherapy-related toxicities. • Active infection requiring systemic treatment or any uncontrolled infection (less than or equal to) 14 days prior to randomization • Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, chronic hepatitis B infection (testing is not required in the absence of clinical suspicion) • Any co-morbid condition that would increase risk of toxicity (eg, suspected or confirmed dihydropyrimidine deficiency) • Other investigational procedures are excluded • Subject currently is enrolled in or (less than or equal to) 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s) • Subject who is pregnant or breast feeding • Man or woman of child-bearing potential not consenting to use adequate contraceptive precautions ie, double barrier contraceptive methods (eg, diaphragm plus condom) during the course of the study and for 6 months after the last investigational product(s) administration for women, and 1 month for men • Subject unwilling or unable to comply with study requirements • Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures • Previously randomized into this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival: time from randomization date to date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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
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End of study will be defined as the date when the last subject completes the final long-term follow-up visit which has been estimated no more than 36 months after the last subject is randomized. |
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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 | |
E.8.9.1 | In the Member State concerned months | 56 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 56 |