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A Preoperative Window of Opportunity Study to Assess the Modulation of Biomarkers in the Primary Tumor Site of Patients With Resectable Oral Cavity Cancer (OCC) Randomized to Receive Preoperative Treatment With PF-00299804

Phase 1/Phase 2
18 Years
Open (Enrolling)
Oral Cavity Cancer

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Trial Information

A Preoperative Window of Opportunity Study to Assess the Modulation of Biomarkers in the Primary Tumor Site of Patients With Resectable Oral Cavity Cancer (OCC) Randomized to Receive Preoperative Treatment With PF-00299804

This is a single-center, randomized, double-blinded, biomarker driven, preoperative window
of opportunity study with a pharmacodynamic primary endpoint. Patients with resectable,
histologically confirmed OCC for whom surgical treatment is planned as definitive
management, will be randomized 2:1 to receive PF-00299804 pre-operatively at a dose of 45 mg
once daily orally for 7-11 days or to Matching Placebo for 7-11 days depending on surgery
schedule. The target is a total of 8 days of treatment but with a minimum of 7 and a maximum
of 11 dosing days. All patients will receive surgery as per standard of care without delay.
Biomarkers from the surgical specimen and baseline tumor biopsy or consent to provide a
tumor block from existing primary diagnostic tumor biopsy completed within 90 days will be
evaluated for primary and secondary pharmacodynamic endpoints.

Inclusion Criteria:

1. Signed written and voluntary informed consent provided.

2. Patient must be willing and able to comply with scheduled visits, treatment plan,
laboratory tests and other study procedures.

3. Age > 18 years, male or female.

4. Patient must be diagnosed with histologically confirmed oral cavity squamous cell
carcinoma (OCC) (lip, floor of mouth, anterior 2/3 tongue, buccal mucosa, upper and
lower gingiva, hard palate and retromolar trigone) considered resectable (T1-4a,
N0-2, M0; (without distant metastases)) for whom surgical resection of the tumor is
planned. Patients with distant metastatic disease or a diagnosis of SCCHN may not be

5. Patient must be able to provide a fresh tumor biopsy prior to randomization for
histopathological and biomarker evaluation. No anti-neoplastic treatment is allowed
between the time from obtaining baseline tumor specimen and randomization. Patients
who decline an in-house fresh pre-treatment tumor biopsy must give consent to provide
a tumor block from an existing diagnostic primary tumor biopsy completed within 90
days of enrolment.

6. Prior treatment with biological agents targeted to the epidermal growth factor
receptor is not allowed.

7. No prior chemotherapy or radiotherapy (to the primary site or nodes).

8. Patient must not have received any prior anti-neoplastic treatment within the past 2

9. Any treatment-related acute toxicity, including laboratory abnormalities, must have
recovered to CTCAE Grade 1 (NCI CTCAE v.4.0) or baseline, except toxicity not
considered a safety risk.

10. ECOG performance status of 0-2.

11. Patient must have adequate organ function as determined by the following criteria:

- Serum creatinine ≤ 1.5 ULN or a calculated creatinine clearance of ≥ 50 mL/min

- Absolute neutrophil count ≥ 1.5 x 109/L

- Leukocytes > 3.0 x 109/L

- Hemoglobin > 80 g/L

- Platelets > 100 x 109/L

- Total bilirubin < ULN

- AST (SGOT) and ALT (SGPT) < 2.5 x ULN

- 12-Lead 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.

- A normal LVEF of >50% as measured by ECHO or MUGA within 4 weeks prior to start
of study treatment will be required for all patients.

Exclusion Criteria:

1. Patients who require segmental mandibulectomy for surgical resection of the oral
cavity tumor will not be enrolled.

2. Primary site of head and neck carcinoma in nasopharynx, skin, or unknown.

3. Prior or concurrent radiation therapy to tumor at site of planned resection.

4. Any clinically significant gastrointestinal abnormalities, which may impair intake,
transit or absorption of PF-00299804.

5. 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.

6. Patients currently taking drugs that are generally accepted to have a risk of causing
Torsades de Pointes

7. 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.

8. Other serious uncontrolled medical disorder or active infection that would impair the
ability to receive study treatment as determined by the investigator.

9. Dementia or significantly altered mental status that would limit the ability to
obtain informed consent and compliance with the requirements of this protocol.

Reproductive Status:

10. Female patients who are breastfeeding or pregnant are excluded. All female patients
with reproductive potential must have a negative pregnancy test within 72 hours prior
to starting treatment.

11. 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. 11. Current enrollment in another therapeutic clinical trial.

12. Inability or lack of willingness to comply with scheduled visits, treatment plans,
protocol assessments or laboratory tests.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

To assess the degree of modulation of the proliferation index, ki-67, in the primary tumor of OCC specimens following a short, preoperative course of PF-00299804

Outcome Time Frame:

8-11 months

Safety Issue:


Principal Investigator

Lillian Siu, MD, FRCPC

Investigator Role:

Principal Investigator

Investigator Affiliation:

Princess Margaret Hospital, Canada


Canada: Ethics Review Committee

Study ID:




Start Date:

May 2010

Completion Date:

September 2013

Related Keywords:

  • Oral Cavity Cancer
  • Oral cavity cancer
  • No prior treatment
  • Mouth Neoplasms