Open-Label Trial Of Oral PF-00299804 By Continuous Dosing In Patients With Recurrent Or Metastatic Head And Neck Squamous Cell Cancer

Study Overview
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Brief Summary
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This study will investigate the safety and efficacy of oral PF-00299804 in patients who have not yet undergone any other drug treatment for recurrent and/ or metastatic head and neck squamous cell cancer.

Official Title
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CLINICAL PHASE 2 MULTICENTER TRIAL OF PF-00299804 IN PATIENTS WITH RECURRENT OR METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: PF-00299804


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent or metastatic Squamous Cell Cancer of the Head and Neck; Measurable disease; Eastern Cooperative Oncology Group (ECOG) 0-1 in Stage 1 = first 23 patients; Eastern Cooperative Oncology Group (ECOG) 0-2 in Stage 2 = 33 patients; Exclusion Criteria: prior therapy for recurrence; platelets < 75,000; prior Epidermal Growth Factor Receptor (EGFR) therapy; interstitial lung disease; primary of nasopharynx

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: PF-00299804<br>* 45 mg by continuous oral dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR) | Percentage of participants with best OR of confirmed CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) relative to total number of evaluable participants for response. CR defined as disappearance of all target/non-target lesions. PR defined as at least a 30 percent (%) decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses (CR and PR) were those that persisted on a follow-up imaging assessment greater than or equal to (≥)4 weeks after the initial objective documentation of response. | Baseline up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DR) | Time in weeks from the first documentation of objective tumor response (CR or PR) to progression or death due to progressive disease (PD). DR was calculated as (the date of the first documentation of PD or death due to PD minus the date of the first CR or PR that was subsequently confirmed plus 1). DR was calculated for the subgroup of participants with a confirmed objective tumor response (CR or PR). | Baseline up to 18 months | 
| Duration of Stable Disease (SD) | Time in weeks from start of treatment to date of objective disease progression (based on RECIST criteria). SD defined as neither sufficient shrinkage for PR nor sufficient increase for PD, taking as a reference the smallest sum of the longest dimensions since treatment start. Participants last known to be alive, not to have started new anticancer treatment, to be progression free, and who had a baseline and at least 1 on-study disease assessment were censored at date of last objective disease assessment that verified lack of PD. Participants who died not due to PD censored on death date. | Baseline up to 18 months | 
| Progression-Free Survival (PFS) | Time in weeks from date of enrollment to first documentation of PD, death due to any cause, symptomatic deterioration, or start of secondary anticancer therapy, whichever occurred first. PFS calculated as (first event date minus enrollment date plus 1). Documentation of progression determined from objective disease assessment based on RECIST criteria. PD defined as at least a 20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since treatment started or the appearance of 1 or more new lesions. | Baseline up to 18 months | 
| Progression-Free Survival (PFS) at 6 Months and at 1 Year | Probability of being event-free (event defined as PD, death due to any cause, symptomatic deterioration, or start of secondary anticancer therapy) at 26 weeks and 52 weeks after the first dose of study treatment. | Baseline up to 52 weeks | 
| Overall Survival (OS) | Time in weeks from the start date of enrollment to date of death due to any cause. OS was calculated as (the death date minus the enrollment date plus 1). Participants without death dates, last known to be alive were censored at last contact. | Baseline up to 18 months | 
| Overall Survival at 6 Months and 1 Year | Probability of survival 26 weeks and 52 weeks after the first dose of study treatment. | Baseline up to Week 52 | 
| Trough Plasma Concentrations (Ctrough) of Dacomitinib After Repeat Dosing | Trough concentrations of dacomitinib in plasma measured as nanograms per milliliter (ng/mL). | Predose on Day 1 of Cycles 2, 3, and 4 and predose on Day 8 of Cycle 1 | 
| Ctrough of Dacomitinib After Repeat Dosing In Participants Requiring Administration of Dacomitinib With a Feeding Tube |  | Predose on Day 1 of Cycles 2, 3, and 4 and predose on Day 8 of Cycle 1 | 
| Maximum Observed Plasma Concentration (Cmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube |  | Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) In Participants Requiring Administration of Dacomitinib With a Feeding Tube | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube |  | Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose | 
| Correlation Between Biomarkers Status and Best Overall Response | The best overall response was best response recorded from the start of the treatment until disease progression/recurrence. In this outcome measure, biomarkers status and best overall response was reported in terms of correlation coefficient. | Baseline up to 18 months | 
| H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | H-score is a measure of the immunohistochemistry staining positivity. The range for H-score is between 0 and 300. A higher score refers to stronger staining of a particular marker. | Baseline up to 18 Months | 
| H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | H-score is a measure of the immunohistochemistry staining positivity. The range for H-score is between 0 and 300. A higher score refers to stronger staining of a particular marker. | Baseline up to 18 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent or metastatic squamous cell cancer of the Head and Neck; no prior systemic therapy for recurrence