Study to Assess Biomarkers in Patients With Resectable Oral Cavity Cancer Randomized to Receive Preoperative Treatment

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01116843
First received: May 3, 2010
Last updated: October 25, 2012
Last verified: October 2012
  Purpose

The objective of this study is to assess the biological effects in the primary tumor following a short, pre-operative course of treatment with PF-00298804 in patients with Oral Cavity Cancer.


Condition Intervention Phase
Oral Cavity Cancer
Drug: PF-00299804/Placebo
Phase 1
Phase 2

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 [ Time Frame: 8-11 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate changes in tissue and blood-based biomarkers before, during and after treatment with PF-00299804 and attempt to correlate with gene expression changes, EGFR variant III mutation status, EGFR amplification and histopathological changes [ Time Frame: 8-11 months ] [ Designated as safety issue: No ]
  • To assess the relationship between pharmacokinetic parameters and molecular changes detected in OCC tumor specimens [ Time Frame: 8-11 months ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability of pre-operative PF-00299804 [ Time Frame: 8-11 months ] [ Designated as safety issue: Yes ]
  • To quantitatively assess the effect of PF-00299804 on tumorigenic cells expressing CD44+/Lin- markers in paired OCC tumor specimens [ Time Frame: 8-11 months ] [ Designated as safety issue: No ]
  • To evaluate gene expression changes in tumor tissue before and after treatment with PF00299804 [ Time Frame: 8-11 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: May 2010
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Patient will receive PF-00299804 pre-operatively at a dose of 45 mg once daily orally for 7-11 days depending on surgery schedule.
Drug: PF-00299804/Placebo
pre-operatively for 7 to 11 days depending on surgery schedule.
Other Names:
  • PF-00299804
  • A7471001
Placebo Comparator: Placebo arm
Patient will receive matching Placebo for 7-11 days depending on surgery schedule.
Drug: PF-00299804/Placebo
pre-operatively for 7 to 11 days depending on surgery schedule.
Other Names:
  • PF-00299804
  • A7471001

Detailed Description:

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.

  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, 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 enrolled.
  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 years.
  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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01116843

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, FRCPC Princess Margaret Hospital, Canada
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01116843     History of Changes
Other Study ID Numbers: WS590266
Study First Received: May 3, 2010
Last Updated: October 25, 2012
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Oral cavity cancer
No prior treatment

Additional relevant MeSH terms:
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Mouth Diseases
Stomatognathic Diseases

ClinicalTrials.gov processed this record on April 20, 2014