| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Cancer of the Head and Neck
|
|
| 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 |
|
| 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 estimate the effect of panitumumab on progression free survival (PFS) when added to combination chemotherapy in first-line treatment of metastatic or recurrent squamous cell carcinoma of head and neck (SCCHN). |
|
| E.2.2 | Secondary objectives of the trial |
1) To estimate the effect of panitumumab on the following endpoints when added to
combination chemotherapy in first-line treatment of metastatic or recurrent SCCHN:
• Overall response rate (ORR)
• Rate of disease control
• Duration of response
• Time to response
• Overall survival (OS)
2) To describe the safety of panitumumab when added to combination chemotherapy
3) To describe PFS, ORR, rate of disease control, duration of response, time to
response, and OS for second-line panitumumab monotherapy (ie, after failure of
combination chemotherapy) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion Criteria
The following inclusion criteria must be met at the time of subject randomization.
Disease Related
• Histologically or cytologically confirmed SCCHN or its variants (eg, basaloid
squamous cell carcinoma and adenosquamous cell carcinoma).
• Primary tumor of the oropharynx, oral cavity, hypopharynx, or larynx, or
SCCHN of unknown primary.
• Diagnosis of metastatic disease and/or recurrent disease determined to be
incurable by surgery or radiotherapy.
• No prior systemic treatment for metastatic and/or recurrent SCCHN
• Subjects who have received radiation as primary therapy are eligible if radiation
therapy treatment was completed > 4 weeks prior to randomization
• Subjects who have previously received chemotherapy as part of the initial
multimodality treatment for locally advanced disease are eligible if the
chemotherapy was completed > 24 weeks prior to randomization
• At least 1 unidimensionally measurable lesion of ≥ 20 mm using conventional
techniques or ≥10 mm with spiral CT scan. Target lesions must not be chosen
from a previously irradiated field unless there had been documented tumor
progression in that lesion prior to randomization
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1
at screening
Demographic
• Men or women age ≥ 18 years
Laboratory
• Adequate hematologic data as follows (≤ 7 days before randomization):
- ANC ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Hemoglobin ≥ 9.0 g/dL
• Adequate renal function (≤ 7 days before randomization):
- Adequate renal function with creatinine clearance ≥ 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)
• Electrolyte function, as follows (≤ 7 days before randomization). If < lower limit of
normal (LLN), subject may receive appropriate treatment and may be
rescreened.
- Magnesium ≥ LLN
- Calcium ≥ LLN (If serum albumin is low, corrected calcium or ionized
calcium should be ≥ LLN)
- Potassium ≥ LLN
• Adequate hepatic function as determined by (≤ 7 days before randomization):
- Aspartate aminotransferase (AST) ≤ 1.5 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) ≤ 1.5 x ULN
- Alkaline phosphatase (ALK-P) ≤ 2.5 x ULN
- Total bilirubin ≤ ULN, unless attributed to Gilbert’s syndrome
• Negative urine or serum pregnancy test ≤ 72 hours prior to randomization
(females of childbearing potential only)
Ethical
• Before any non-standard of care study-specific procedure, subjects or their
legally acceptable representative must be able to comprehend and have signed
and dated the applicable independent ethics committee (IEC) or institutional
review board (IRB) approved written Informed Consent Form (ICF). |
|
| E.4 | Principal exclusion criteria |
Exclusion Criteria
Subjects who meet any of the following criteria at the time of randomization must be
excluded from participation in this study.
Disease Related
• Documented or symptomatic central nervous system (CNS) metastases
• Nasopharyngeal carcinoma
• History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or
evidence of interstitial lung disease on baseline chest computerized tomography
(CT) scan
• 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 ≥ 3 years prior to
randomization
• Clinically significant cardiovascular disease (including myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled
cardiac arrhythmia) ≤ 1 year of 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
• Pulmonary embolism, deep vein thrombosis, or other significant thromboembolic
event ≤ 8 weeks prior to randomization
• Symptomatic peripheral neuropathy of Grade ≥ 2 based on the CTCAE v3.0
(Symptomatic weakness and/ or sensory alteration or paresthesia (tingling) that
is interfering with function but not interfering with Activities of Daily Living
[ADL])
• Subjects not recovered from all previous acute radiotherapy-related toxicities to ≤
grade 1
• History of severe skin disorder that in the opinion of the investigator may interfere
with study conduct
• Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C
virus, acute or chronic hepatitis B infection
• Any co-morbid disease that would increase risk of toxicity
• History of any medical, or psychiatric condition, or laboratory abnormality that in
the opinion of the investigator may increase the risks associated with the study
participation, or may interfere with the interpretation of the results
• Active infection requiring systemic treatment or any uncontrolled infection ≤ 14
days prior to randomization
• Hearing loss of Grade ≥ 3 based on the CTCAE v3.0 Auditory/Ear (Hearing loss
requiring hearing aid or intervention (ie, interfering with ADL [without monitoring
program])
Medications and Treatments
• Known allergy or hypersensitivity to panitumumab, or other study medications.
• Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment with small
molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib) unless received as
part of prior multimodality treatment (eg, as a radiation sensitizer) and
completed > 24 weeks prior to randomization.
• Subject is currently enrolled in or ≤ 30 days since ending other investigational
device, investigational procedure, or drug study(s), or subject is receiving other
investigational agent(s)
• Subjects requiring use of immunosuppressive agents (eg, methotrexate and
cyclosporine), however, corticosteroids are allowed
General
• Man or woman of child-bearing potential (women who are post-menopausal < 52
weeks, not surgically sterilized, or not abstinent) who do not consent to use
adequate contraceptive precautions (per institutional standard of care) during the
course of the study, and for 24 weeks after the last dose of therapy
administration for women and 4 weeks for men.
• Female subject who is pregnant or breast-feeding
• Subject unwilling or unable to comply with study requirements
• Major surgery requiring general anesthesia/ spinal anesthesia and a significant
incision (ie, larger than what is required for placement of central venous access,
percutaneous feeding tube, or biopsy) ≤ 28 days or minor surgery (excluding
central venous placement, percutaneous feeding tube, and biopsy) ≤ 14 days
prior to randomization. Subjects must have recovered from surgery-related
toxicities.
• Any kind of disorder that compromises the ability of the subject to give written
informed consent and/or to comply with study
• Previously randomized into this study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is PFS during the first-line treatment phase. Duration of PFS is
defined as the time from the date of randomization to the first date of observed disease progression, as defined by modified RECIST, or death due to any cause, (whichever comes first). Subjects who are alive and have not progressed will be censored at the date of last evaluable disease assessment during the first-line treatment phase. |
|
| 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 | 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 | 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 | 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 | 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| 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 | 6 |
| 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 |
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