Pharmacokinetic Assessment of PF-00299804 in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Following Administration Through a Gastrojejunostomy Feeding Tube
1. Signed written and voluntary informed consent provided.
2. Patient must be willing and able to comply with scheduled visits, treatment plan,
pharmacokinetic assessments, laboratory tests and other study procedures.
3. Age ≥ 18 years, male or female.
4. Patient must be diagnosed with histologically or cytologically confirmed SCCHN. Other
primary sites of head and neck carcinoma including nasopharynx, skin, maxillary sinus
or unknown primary, are allowed.
5. Patient must have a functioning gastrojejunostomy tube.
6. Patient may be receiving concurrent chemoradiation or radiation alone or may have
recently completed surgery for locally advanced disease.
7. Prior treatment with biological agents targeted to the epidermal growth factor
receptor is not allowed.
8. Any treatment-related acute toxicity, including laboratory abnormalities, must have
recovered to CTCAE Grade 2 (NCI CTCAE v.4.0) or baseline, except toxicity not
considered a safety risk. Chronic dysphagia or xerostomia or other local effect
resulting from prior surgery or radiation will not be considered an exclusion
criterion if remaining stable for ≥ 3 months prior to study enrollment.
9. ECOG performance status of 0-2.
10. Patient must have adequate organ function as determined by the following criteria
- Renal function:
- Serum creatinine ≤ 1.5 ULN (upper limit of normal range) or a calculated
creatinine clearance of ≥ 50 mL/min using the following formula: Creatinine
clearance = [(140-age) x wt (kg) x Constant] / creatinine (µmol/L)
[Constant = 1.23 for men and 1.04 for women]
- Bone marrow function: (without hematopoietic growth factors or transfusion)
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Leukocytes ≥ 3.0 x 109/L
- Hemoglobin ≥ 80 g/L (or > 8 g/dL)
- Platelets ≥ 100 x 109/L
- Liver function:
- Total bilirubin ≤ ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN
- Cardiac function:
- 12-Lead electrocardiogram (ECG) with normal tracing, or clinically
non-significant changes that do not require medical intervention.
- QTc interval ≤ 470 msec, and without history of Torsades de Pointes or
other symptomatic QTc abnormality.
1. Patient cannot be concurrently enrolled on another clinical trial while enrolled on
2. Prior investigational drug therapy within 30 days or 5 half lives preceding the first
dose of study medication (whichever is longer).
3. Requirement for treatment with drugs that are highly dependent on CYP2D6 for
metabolism since PF-00299804 is a potent CYP2D6 inhibitor in in vitro assays. These
include: S-metoprolol, propafenone, timolol, amitriptyline, clomipramine,
desipramine, imipramine, paroxetine, haloperidol, risperidone, thioridazine, codeine,
dextromethorphan, flecainide, mexiletine, tamoxifen, venlafaxine. Lidocaine may be
used with clinical monitoring (including telemetry). Other opiates such as morphine,
oxycodone, dihydrocodeine, hydrocodone, and tramadol can be used as substitutes to
replace codeine. Use of these opiates should be monitored for altered analgesia
during treatment with PF-00299804 as they may be partly metabolized by CYP2D6. [This
restriction may be modified if the results from drug-drug interaction (DDI) study
A7471014 (CYP2D6 inhibition) indicate no clinically significant effect of PF-00299804
on the metabolism of CYP2D6 metabolized medications].
4. Patients currently taking drugs that are generally accepted to have a risk of causing
Torsades de Pointes including:
- quinidine, procainamide, disopyramide;
- amiodarone, sotalol, ibutilide, dofetilide;
- erythromycin, clarithromycin;
- chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide;
- cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
5. Any acute or chronic medical or psychiatric condition or laboratory abnormality that
could increase the risk associated with trial participation or trial drug
administration or could interfere with the interpretation of trial results and, in
the judgment of the investigator, would make the patient inappropriate for entry in
the trial. This includes:
- History of interstitial lung disease;
- Uncontrolled hypertension, unstable angina, myocardial infarction or symptomatic
congestive heart failure within the past 12 months or serious uncontrolled
cardiac arrhythmia, diagnosed or suspected congenital long QT syndrome;
- Patients with any history of cardiovascular disease (uncontrolled hypertension,
ischemic heart disease, congestive heart failure, stroke, deep vein thrombosis,
or at stable minimally symptomatic status, for 6 months prior to enrollment
during which they have not required antiarrhythmics or clinically significant
change in medical management;
- Active bacterial, fungal or viral infection including hepatitis B (HBV),
hepatitis C (HCV), and human immunodeficiency virus (HIV). Serological testing
will not be required at baseline for patients who have no symptoms suggestive of
- History of significant bleeding disorder, or concurrent medications that are
felt in the opinion of the investigator to potentially lead to unacceptable
coagulation function during perioperative interval, including:
- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease);
- Diagnosed acquired bleeding disorder within one year (e.g., acquired
anti-factor VIII antibodies).
6. Other serious uncontrolled medical disorder or active infection that would impair the
ability to receive study treatment as determined by the investigator.
7. Dementia or significantly altered mental status that would limit the ability to
obtain informed consent and compliance with the requirements of this protocol.
8. Female patients who are breastfeeding or pregnant are excluded. All female patients
with reproductive potential must have a negative pregnancy test (serum/urine) within
72 hours prior to starting treatment. Female patients of reproductive potential
include any female who has experienced menarche and who has not undergone successful
surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral
oophorectomy) or is not postmenopausal (defined as amenorrhea >12 consecutive months;
or women on hormone replacement therapy (HRT) with documented serum follicle
stimulating hormone (FSH) level >35 mL.U/mL).
9. Female patients of reproductive potential or their partners must agree to use
effective contraception while receiving trial treatment and for at least 3 months
thereafter. The definition of effective contraception will be based on the judgment
of the principal investigator or designated associate.
10. Inability or lack of willingness to comply with scheduled visits, treatment plans,
protocol assessments or laboratory tests.