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A Study of PF-00299804 When Given Through a Feeding Tube in Locally Advanced Head and Neck Squamous Cell Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01484847
First received: September 30, 2011
Last updated: May 28, 2013
Last verified: May 2013
  Purpose

This is a study to assess how much of the investigational drug, PF-00298804, is in the blood stream over a period of time (called pharmacokinetic tests or PK) in patients with locally advanced head and neck squamous cell carcinoma who have a (gastrojejunostomy) feeding tube.


Condition Intervention
Head and Neck Squamous Cell Carcinoma
Drug: PF-00299804

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Pharmacokinetic Assessment of PF-00299804 in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Following Administration Through a Gastrojejunostomy Feeding Tube

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Composite (or Profile) of Pharmacokinetics Time Frame: predose, 0,1,2,3,4,6,8,12,24,48,72, 96 hours post-dose [ Time Frame: 3-6 months ] [ Designated as safety issue: No ]
    Cmax, Area Under Curve, Tmax


Secondary Outcome Measures:
  • Comparison of pharmacokinetic parameters of study subjects with existing phase I pharmacokinetic data following administration of PF-00299804. [ Time Frame: 3-6 months ] [ Designated as safety issue: No ]
    Tmax=4-24 hrs, Cmax = 28.1 ng/ml, AUCtau=47 hr*ng/ml, t1/2=85.1

  • Overall safety profile as per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. [ Time Frame: 3-6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: December 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Head and neck cancer
Locally advanced head and neck squamous cell carcinoma
Drug: PF-00299804
Tablet, single dose of 45 mg via gastrojejunostomy tube on an empty stomach

Detailed Description:

This is a single arm pharmacokinetic assessment study conducted at Princess Margaret Hospital in which eligible patients will be enrolled successively to receive a single dose of PF-00299804 in an open-labelled, unblinded manner. All patients will receive 45 mg of PF-00299804 via Gastrostomy (GT) once only on an empty stomach (i.e. 2 hours before or after oral food intake or GT feeds (food intake of less than 500 calories permitted)) as an inpatient. All patients will be admitted for an overnight inpatient stay (approximately 24 hours) to facilitate pharmacokinetic assessment. There will be no dose reductions or modifications. Blood sampling for pharmacokinetics will occur on day 1 immediately prior to the dose of PF-00299804 (t=0), then at t=30 minutes, t=1 hour, t=2 hours, t=3 hours, t=4 hours, t=6 hours, t=12 hours, t=24 hours, t=48 hours, t=72 hours, t=96 hours, t=144 hours, t=168 hours, t=192 hours, and t=216 hours.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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 for:

    • 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.

Exclusion Criteria:

  1. Patient cannot be concurrently enrolled on another clinical trial while enrolled on this study.
  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 infection.
    • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01484847

Locations
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Pfizer
Investigators
Principal Investigator: Lillian Siu, MD University Health Network/Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01484847     History of Changes
Other Study ID Numbers: WS1544542/Pan-HER-GT-001
Study First Received: September 30, 2011
Last Updated: May 28, 2013
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by University Health Network, Toronto:
advanced
PF-00299804
head and neck
pharmacokinetic
squamous cell carcinoma
gastrojejunostomy
feeding tube

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell

ClinicalTrials.gov processed this record on November 23, 2014