PF-00299804 in Patients With Head and Neck Squamous Cell Carcinoma

Phase II Trial of PF-00299804 in Patients With Metastatic/Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) After Failure of Platinum-containing Therapy

Epidermal growth factor receptor (EGFR) is often over-expressed, and have been related to poor prognosis in patients with HNSCC. EGFR targeting strategies showed clinical anti-tumor efficacy in patients with HNSCC. PF-00299804 is a second-generation quinazoline-based irreversible pan-HER inhibitor. In preclinical studies, PF-00299804 has much lower IC50 values than gefitinib in cell lines engineered to express EGFRvIII mutations (1.2 nM versus 2,700 nM) and produces tumor growth inhibition in gefitinib-resistant xenografts. A phase II trial of PF-00299804 in patients with recurrent or metastatic HNSCC is currently ongoing and preliminary report in ASCO 2010 showed its anti-tumor activity against HNSCC. The investigators suggest a phase II trial of pan-HER inhibitor PF-00299804 in patients with recurrent or metastatic HNSCC previously treated with platinum-based chemotherapy.

Study Overview

• Status: Completed
• Conditions: Head Neck Cancer Squamous Cell Recurrent; Head Neck Cancer Squamous Cell Metastatic
• Intervention / Treatment: Drug: PF-00299804

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of
    • Dongsan Medical Center
  • Daegu, Korea, Republic of
    • Chilgok Kyungpook National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed squamous cell carcinoma of head and neck
• Age ≥ 18
• ECOG PS 0-2
• Documented progressive disease after platinum-based systemic chemotherapy (either cisplatin or carboplatin) with or without cetuximab
• At least one bidimensionally measurable disease
• Adequate organ function for treatment
• Availability of tumor tissue for molecular analysis (archival or rebiopsy tissue)

Exclusion Criteria:

• Nasopharyngeal carcinoma
• Eligibility for local therapy (surgery or radiotherapy)
• Previous treatment with small molecule EGFR tyrosine kinase inhibitors
• More than one systemic chemotherapy
• Any major operation or irradiation within 4 weeks of baseline disease assessment
• Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
• CNS metastasis with continuous corticosteroid use within 4 weeks of baseline disease assessment
• Patients with known interstitial lung disease
• Patients with uncontrolled or significant cardiovascular disease (AMI within 12 months, Unstable angina within 6 months, NYHA Class III, IV Congestive heart failure or left ventricular ejection fraction below local institutional lower limit of normal or below 45%, Congenital long QT syndrome, Any significant ventricular arrhythmia, Any uncontrolled second or third degree heart block, Uncontrolled hypertension)
• Concomitant malignancy (except adequately treated basal cell cancer of skin or cervical cancer in situ)
• Pregnant or breast-feeding women
• Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-00299804	Drug: PF-00299804; 45 mg P.O. Daily (28-day treatment as one treatment cycle)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Tumor assessment by RECIST criteria version 1.1 will be followed every 8 weeks treatment until disease progression	every 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best objective response	Tumor assessment by RECIST criteria version 1.1 will be followed every 8 weeks treatment until disease progression	every 8 weeks
Progression-free survival	from C1D1 until confirmed disease progression or death	every 8 weeks
Overall survival	from C1D1 to death	every 12 weeks
Toxicity profile	from C1D1 to 1 months after the last dose adminitration	every 4 weeks

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Byoung Chul Cho, M.D.,Ph.D., Yonsei University

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: October 4, 2011
• First Submitted That Met QC Criteria: October 6, 2011
• First Posted (Estimate): October 10, 2011

Study Record Updates

• Last Update Posted (Estimate): September 30, 2014
• Last Update Submitted That Met QC Criteria: September 28, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: PF-00299804, head and neck cancer, squamous cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Squamous Cell
• Other Study ID Numbers: 4-2011-0434