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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00768664
• Collaborator: (none)
• Enrollment: 69
• Locations: 10
• Arm: 1
• Actual Duration (Months): 41.4
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Neoplasms	Drug: PF-00299804	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Non-Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CLINICAL PHASE 2 MULTICENTER TRIAL OF PF-00299804 IN PATIENTS WITH RECURRENT OR METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
• Actual Study Start Date: Nov 4, 2008
• Actual Primary Completion Date: May 5, 2010
• Actual Study Completion Date: Apr 18, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: PF-00299804; 45 mg by continuous oral dosing

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR) [Baseline up to 18 months]

   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.

Secondary Outcome Measures

1. Duration of Response (DR) [Baseline up to 18 months]

   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).

2. Duration of Stable Disease (SD) [Baseline up to 18 months]

   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.

3. Progression-Free Survival (PFS) [Baseline up to 18 months]

   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.

4. Progression-Free Survival (PFS) at 6 Months and at 1 Year [Baseline up to 52 weeks]

   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.

5. Overall Survival (OS) [Baseline up to 18 months]

   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.

6. Overall Survival at 6 Months and 1 Year [Baseline up to Week 52]

   Probability of survival 26 weeks and 52 weeks after the first dose of study treatment.

7. Trough Plasma Concentrations (Ctrough) of Dacomitinib After Repeat Dosing [Predose on Day 1 of Cycles 2, 3, and 4 and predose on Day 8 of Cycle 1]

   Trough concentrations of dacomitinib in plasma measured as nanograms per milliliter (ng/mL).

8. 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]

9. 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]

10. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 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 plasma concentration time-curve from zero to the last measured concentration (AUClast).

11. 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]

12. Plasma Decay Half-Life (t1/2) [Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

13. Correlation Between Biomarkers Status and Best Overall Response [Baseline up to 18 months]

    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.

14. H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers [Baseline up to 18 Months]

    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.

15. H-Score at Ratio to Baseline for Paired Biopsy Biomarkers [Baseline up to 18 Months]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BC Cancer Agency, Vancouver Centre	Vancouver	British Columbia	Canada	V5Z 4E6
2	Fairmont Medical Building	Vancouver	British Columbia	Canada	V5Z1H7
3	Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
4	London Health Sciences Centre	London	Ontario	Canada	N6A 4L6
5	London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
6	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
7	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1Y 4K7
8	Sunnybrook Health Sciences Centre: Odette Cancer Center	Toronto	Ontario	Canada	M4N 3M5
9	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
10	Hopital Notre-dame du CHUM - Oncology Center	Montreal	Quebec	Canada	H2L 4M1

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00768664
• Other Study ID Numbers: A7471027
• First Posted: Oct 8, 2008
• Last Update Posted: Feb 9, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: recurrent or metastatic squamous cell cancer of the Head and Neck; no prior systemic therapy for recurrence
• Additional relevant MeSH terms: Head and Neck Neoplasms

Study Results

Participant Flow

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Period Title: Overall Study
STARTED	69
COMPLETED	0
NOT COMPLETED	69

Baseline Characteristics

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Overall Participants	69
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.9 (9.0)
Sex: Female, Male (Count of Participants)
Female	8 11.6%
Male	61 88.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR)
Description	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.
Time Frame	Baseline up to 18 months

Outcome Measure Data

Analysis Population Description

Response-Evaluable Population: All participants with measurable disease (per RECIST), treated, with baseline and ≥1 on-study assessment. Participants who discontinued early before on-study tumor assessment due to PD were evaluable, but not if discontinued early due to reasons such as participant request, lack of compliance, or early toxicity.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	63
Number (95% Confidence Interval) [Percentage of participants]	12.5 18.1%

2. Secondary Outcome

Title	Duration of Response (DR)
Description	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).
Time Frame	Baseline up to 18 months

Outcome Measure Data

Analysis Population Description

Response Evaluable population; n equals (=) number of participants with an objective response of CR or PR.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	8
Median (95% Confidence Interval) [weeks]	17.9

3. Secondary Outcome

Title	Duration of Stable Disease (SD)
Description	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.
Time Frame	Baseline up to 18 months

Outcome Measure Data

Analysis Population Description

Response Evaluable population; n=number of participants with a best overall response of SD.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	36
Median (95% Confidence Interval) [weeks]	14.6

4. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	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.
Time Frame	Baseline up to 18 months

Outcome Measure Data

Analysis Population Description

ITT Population: all enrolled participants.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	69
Median (95% Confidence Interval) [weeks]	12.1

5. Secondary Outcome

Title	Progression-Free Survival (PFS) at 6 Months and at 1 Year
Description	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.
Time Frame	Baseline up to 52 weeks

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	69
Probability of being event free at Week 26	21.4
Probability of being event free at Week 52	2.1

6. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	Baseline up to 18 months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	69
Median (95% Confidence Interval) [weeks]	34.6

7. Secondary Outcome

Title	Overall Survival at 6 Months and 1 Year
Description	Probability of survival 26 weeks and 52 weeks after the first dose of study treatment.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	69
Survival Probability at Week 26	66.5
Survival Probability at Week 52	39.6

8. Secondary Outcome

Title	Trough Plasma Concentrations (Ctrough) of Dacomitinib After Repeat Dosing
Description	Trough concentrations of dacomitinib in plasma measured as nanograms per milliliter (ng/mL).
Time Frame	Predose on Day 1 of Cycles 2, 3, and 4 and predose on Day 8 of Cycle 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population: all enrolled participants who received at least 1 dose of study medication from whom at least 1 PK sample was obtained. Here, "Overall number of participants analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies participants evaluable for specific rows.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	63
Cycle 1 Day 8	64.30
Cycle 2 Day 1	76.85
Cycle 3 Day 1	74.50
Cycle 4 Day 1	69.60

9. Secondary Outcome

Title	Ctrough of Dacomitinib After Repeat Dosing In Participants Requiring Administration of Dacomitinib With a Feeding Tube
Time Frame	Predose on Day 1 of Cycles 2, 3, and 4 and predose on Day 8 of Cycle 1

Outcome Measure Data

Analysis Population Description

PK population: all enrolled participants who received at least 1 dose of study medication from whom at least 1 PK sample was obtained. Here, "Overall number of participants analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies participants evaluable for specific rows.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	7
Cycle 1 Day 8	81.30
Cycle 2 Day 1	92.05
Cycle 3 Day 1	129.2
Cycle 4 Day 1	156

10. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube
Time Frame	Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

PK Population; n=number of participants requiring administration of dacomitinib with a feeding tube.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	1
Median (Full Range) [ng/mL]	23.80

11. Secondary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) In Participants Requiring Administration of Dacomitinib With a Feeding Tube
Description	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time Frame	Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

PK Population; n=number of participants requiring administration of dacomitinib with a feeding tube.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	1
Median (Full Range) [ng*hour (hr)/mL]	285.0

12. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube
Time Frame	Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

PK Population; n=number of participants requiring administration of dacomitinib with a feeding tube.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	1
Median (Full Range) [hours]	4.00

13. Secondary Outcome

Title	Plasma Decay Half-Life (t1/2)
Description	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame	Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

PK Population; n=number of participants requiring administration of dacomitinib with a feeding tube.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	1
Median (Full Range) [hours]	NA

14. Secondary Outcome

Title	Correlation Between Biomarkers Status and Best Overall Response
Description	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.
Time Frame	Baseline up to 18 months

Outcome Measure Data

Analysis Population Description

Biomarker analysis set: all enrolled participants who had baseline samples submitted as per Institutional Review Board/Independent Ethics Committee approval and participant consent. Here, "number analyzed" signifies participants evaluable at specific rows.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	48
HPV Overall Status	0.799
EGFR VIII Status with DNA Method	1.000
PTEN:	0.840
Mutation	1.000

15. Secondary Outcome

Title	H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers
Description	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.
Time Frame	Baseline up to 18 Months

Outcome Measure Data

Analysis Population Description

Biomarker analysis set: all enrolled participants who had baseline samples submitted as per Institutional Review Board/Independent Ethics Committee approval and participant consent. Here, "Overall number of participants analyzed" signifies participants evaluable for this outcome measures and "number analyzed" signifies participants evaluable at specific rows.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	13
Cytoplasm: AKT: at baseline	99.1 (77.90)
Cytoplasm: AKT: at Cycle 1 Day 8	123.8 (77.83)
Cytoplasm: CC3: at baseline	22.1 (28.86)
Cytoplasm: CC3: at Cycle 1 Day 8	17.9 (27.41)
Cytoplasm: EGFR: at baseline	190.4 (113.11)
Cytoplasm: EGFR: at Cycle 1 Day 8	184.4 (113.01)
Cytoplasm: ERK: at baseline	148.1 (74.26)
Cytoplasm: ERK: at Cycle 1 Day 8	126.5 (63.80)
Cytoplasm: HER2: at baseline	36.8 (52.60)
Cytoplasm: HER2: at Cycle 1 Day 8	43.0 (49.51)
Cytoplasm: HER3: at baseline	60.6 (62.49)
Cytoplasm: HER3: at Cycle 1 Day 8	50.2 (42.41)
Cytoplasm: pEGFR: at baseline	101.2 (72.01)
Cytoplasm: pEGFR: at Cycle 1 Day 8	115.6 (56.35)
Cytoplasm: pEGFR: ratio to baseline	1.0 (0.47)
Cytoplasm: MET: at baseline	70.0 (37.31)
Cytoplasm: MET: at Cycle 1 Day 8	81.6 (54.84)
Cytoplasm: pAKT: at baseline	41.9 (51.71)
Cytoplasm: pAKT: at Cycle 1 Day 8	31.4 (54.78)
Cytoplasm: pERK: at baseline	103.3 (46.36)
Cytoplasm: pERK: at Cycle 1 Day 8	88.3 (41.51)
Cytoplasm: pHER2: at baseline	81.6 (31.79)
Cytoplasm: pHER2: at Cycle 1 Day 8	78.5 (39.37)
Cytoplasm: pMET: at baseline	0.0 (0.00)
Cytoplasm: pMET: at Cycle 1 Day 8	0.0 (0.00)
Membrane: EGFR: at baseline	258.3 (60.41)
Membrane: EGFR: at Cycle 1 Day 8	209.4 (99.88)
Membrane: HER2: at baseline	8.2 (24.01)
Membrane: HER2: at Cycle 1 Day 8	4.3 (8.58)
Membrane: HER3: at baseline	12.2 (27.29)
Membrane: HER3: at Cycle 1 Day 8	9.6 (16.09)
Membrane: MET: at baseline	66.3 (71.26)
Membrane: MET: at Cycle 1 Day 8	53.9 (57.83)
Membrane: pEGFR: at baseline	5.8 (14.27)
Membrane: pEGFR: at Cycle 1 Day 8	4.5 (7.27)
Membrane pHER2: at baseline	1.6 (2.57)
Membrane pHER2: at Cycle 1 Day 8	5.8 (9.28)
Membrane: pMET: at baseline	0.0 (0.00)
Membrane: pMET: at Cycle 1 Day 8	0.0 (0.00)
Nucleus: AKT: at baseline	87.5 (67.31)
Nucleus: AKT: at Cycle 1 Day 8	111.8 (72.93)
Nucleus: ERK: at baseline	152.3 (95.93)
Nucleus: ERK: at Cycle 1 Day 8	117.5 (73.69)
Nucleus: pAKT: at baseline	40.6 (53.37)
Nucleus: pAKT: at Cycle 1 Day 8	19.1 (38.07)
Nucleus: pERK: at baseline	152.7 (88.08)
Nucleus: pERK: at Cycle 1 Day 8	144.8 (76.57)

16. Secondary Outcome

Title	H-Score at Ratio to Baseline for Paired Biopsy Biomarkers
Description	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.
Time Frame	Baseline up to 18 Months

Outcome Measure Data

Analysis Population Description

Biomarker analysis set: all enrolled participants who had baseline samples submitted as per Institutional Review Board/Independent Ethics Committee approval and participant consent. Here, "Overall number of participants analyzed" signifies participants evaluable for this outcome measures and "number analyzed" signifies participants evaluable at specific rows.

Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
Measure Participants	13
Cytoplasm: AKT	2.0 (3.03)
Cytoplasm: CC3	1.0 (0.63)
Cytoplasm: EGFR	1.0 (0.17)
Cytoplasm: ERK	0.9 (0.29)
Cytoplasm: HER2	0.7 (0.50)
Cytoplasm: HER3	0.7 (0.60)
Cytoplasm: pEGFR	1.0 (0.47)
Cytoplasm: MET	1.2 (0.44)
Cytoplasm: pAKT	0.3 (0.28)
Cytoplasm: pERK	0.9 (0.35)
Cytoplasm: pHER2	0.8 (0.42)
Membrane: EGFR	0.8 (0.33)
Membrane: HER2	0.3 (NA)
Membrane: HER3	0.6 (0.50)
Membrane: MET	0.8 (0.41)
Membrane: pEGFR	2.5 (4.33)
Membrane pHER2	4.3 (4.50)
Nucleus: AKT	2.8 (4.73)
Nucleus: ERK	1.1 (1.38)
Nucleus: pAKT	0.3 (0.59)
Nucleus: pERK	0.9 (0.33)

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Dacomitinib 45 mg
Arm/Group Description	Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed.
All Cause Mortality
	Dacomitinib 45 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dacomitinib 45 mg
	Affected / at Risk (%)	# Events
Total	20/69 (29%)
Blood and lymphatic system disorders
Anaemia	1/69 (1.4%)
Cardiac disorders
Angina pectoris	1/69 (1.4%)
Atrial fibrillation	1/69 (1.4%)
Cardio-respiratory arrest	1/69 (1.4%)
Gastrointestinal disorders
Diarrhoea	4/69 (5.8%)
Dysphagia	1/69 (1.4%)
Nausea	1/69 (1.4%)
Vomiting	2/69 (2.9%)
General disorders
Chest pain	1/69 (1.4%)
Disease progression	4/69 (5.8%)
Infections and infestations
Brain abscess	1/69 (1.4%)
Cellulitis	1/69 (1.4%)
Pneumonia	1/69 (1.4%)
Sepsis	1/69 (1.4%)
Septic shock	1/69 (1.4%)
Injury, poisoning and procedural complications
Pelvic fracture	1/69 (1.4%)
Investigations
Blood creatinine increased	1/69 (1.4%)
Metabolism and nutrition disorders
Decreased appetite	1/69 (1.4%)
Dehydration	2/69 (2.9%)
Hypercalcaemia	1/69 (1.4%)
Hyperglycaemia	1/69 (1.4%)
Hyponatraemia	1/69 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin	1/69 (1.4%)
Nervous system disorders
Cerebral infarction	1/69 (1.4%)
Motor dysfunction	1/69 (1.4%)
Renal and urinary disorders
Urinary retention	1/69 (1.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/69 (1.4%)
Haemoptysis	1/69 (1.4%)
Laryngeal oedema	1/69 (1.4%)
Pneumonia aspiration	2/69 (2.9%)
Pneumothorax	1/69 (1.4%)
Pulmonary embolism	1/69 (1.4%)
Respiratory disorder	1/69 (1.4%)
Vascular disorders
Haemorrhage	1/69 (1.4%)
Other (Not Including Serious) Adverse Events
	Dacomitinib 45 mg
	Affected / at Risk (%)	# Events
Total	68/69 (98.6%)
Blood and lymphatic system disorders
Anaemia	1/69 (1.4%)
Cardiac disorders
Atrial flutter	1/69 (1.4%)
Left ventricular dysfunction	1/69 (1.4%)
Pericardial effusion	1/69 (1.4%)
Ear and labyrinth disorders
Deafness	3/69 (4.3%)
Hearing impaired	1/69 (1.4%)
Endocrine disorders
Hypothyroidism	3/69 (4.3%)
Eye disorders
Blepharitis	3/69 (4.3%)
Conjunctival irritation	1/69 (1.4%)
Conjunctivitis	6/69 (8.7%)
Dry eye	2/69 (2.9%)
Entropion	1/69 (1.4%)
Eye discharge	1/69 (1.4%)
Eye irritation	1/69 (1.4%)
Eye oedema	1/69 (1.4%)
Eye pain	1/69 (1.4%)
Eye pruritus	2/69 (2.9%)
Eyelids pruritus	1/69 (1.4%)
Lacrimation increased	1/69 (1.4%)
Ocular hyperaemia	1/69 (1.4%)
Vision blurred	3/69 (4.3%)
Visual impairment	1/69 (1.4%)
Gastrointestinal disorders
Abdominal discomfort	1/69 (1.4%)
Abdominal pain	5/69 (7.2%)
Abdominal pain upper	1/69 (1.4%)
Anorectal disorder	1/69 (1.4%)
Aptyalism	1/69 (1.4%)
Cheilitis	6/69 (8.7%)
Constipation	7/69 (10.1%)
Diarrhoea	58/69 (84.1%)
Dry mouth	5/69 (7.2%)
Dyspepsia	7/69 (10.1%)
Dysphagia	8/69 (11.6%)
Eructation	1/69 (1.4%)
Flatulence	1/69 (1.4%)
Gingival pain	1/69 (1.4%)
Glossodynia	3/69 (4.3%)
Lip dry	2/69 (2.9%)
Lip haemorrhage	1/69 (1.4%)
Lip pain	1/69 (1.4%)
Mouth haemorrhage	1/69 (1.4%)
Mouth ulceration	1/69 (1.4%)
Nausea	15/69 (21.7%)
Odynophagia	1/69 (1.4%)
Oral pain	3/69 (4.3%)
Proctalgia	1/69 (1.4%)
Proctitis	1/69 (1.4%)
Rectal haemorrhage	1/69 (1.4%)
Saliva altered	1/69 (1.4%)
Salivary hypersecretion	1/69 (1.4%)
Stomatitis	23/69 (33.3%)
Vomiting	10/69 (14.5%)
General disorders
Adverse drug reaction	1/69 (1.4%)
Asthenia	2/69 (2.9%)
Chest pain	5/69 (7.2%)
Chills	4/69 (5.8%)
Face oedema	3/69 (4.3%)
Fatigue	35/69 (50.7%)
Influenza like illness	1/69 (1.4%)
Irritability	1/69 (1.4%)
Local swelling	1/69 (1.4%)
Mucosal inflammation	11/69 (15.9%)
Oedema peripheral	6/69 (8.7%)
Performance status decreased	1/69 (1.4%)
Pyrexia	5/69 (7.2%)
Infections and infestations
Candidiasis	3/69 (4.3%)
Cystitis	1/69 (1.4%)
Fungal infection	1/69 (1.4%)
Groin infection	1/69 (1.4%)
Localised infection	1/69 (1.4%)
Nasopharyngitis	2/69 (2.9%)
Oral candidiasis	2/69 (2.9%)
Otitis media	1/69 (1.4%)
Paronychia	12/69 (17.4%)
Pneumonia	3/69 (4.3%)
Rhinitis	6/69 (8.7%)
Skin infection	1/69 (1.4%)
Tinea pedis	2/69 (2.9%)
Urinary tract infection	1/69 (1.4%)
Injury, poisoning and procedural complications
Excoriation	2/69 (2.9%)
Eye penetration	1/69 (1.4%)
Fall	1/69 (1.4%)
Post procedural haemorrhage	1/69 (1.4%)
Procedural site reaction	1/69 (1.4%)
Radiation skin injury	1/69 (1.4%)
Investigations
Alanine aminotransferase increased	2/69 (2.9%)
Aspartate aminotransferase increased	2/69 (2.9%)
Blood creatinine increased	2/69 (2.9%)
Haemoglobin decreased	1/69 (1.4%)
Weight decreased	12/69 (17.4%)
Metabolism and nutrition disorders
Decreased appetite	18/69 (26.1%)
Dehydration	6/69 (8.7%)
Hypercalcaemia	2/69 (2.9%)
Hyperkalaemia	1/69 (1.4%)
Hypokalaemia	3/69 (4.3%)
Hypomagnesaemia	3/69 (4.3%)
Hyponatraemia	2/69 (2.9%)
Hypophosphataemia	2/69 (2.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/69 (1.4%)
Back pain	6/69 (8.7%)
Bone pain	1/69 (1.4%)
Fistula	3/69 (4.3%)
Flank pain	1/69 (1.4%)
Hypercreatinaemia	1/69 (1.4%)
Muscular weakness	1/69 (1.4%)
Musculoskeletal chest pain	1/69 (1.4%)
Musculoskeletal pain	2/69 (2.9%)
Myalgia	1/69 (1.4%)
Neck pain	1/69 (1.4%)
Pain in jaw	1/69 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm	1/69 (1.4%)
Keratoacanthoma	1/69 (1.4%)
Tumour haemorrhage	1/69 (1.4%)
Tumour pain	4/69 (5.8%)
Nervous system disorders
Cognitive disorder	1/69 (1.4%)
Dizziness	5/69 (7.2%)
Dysgeusia	2/69 (2.9%)
Headache	5/69 (7.2%)
Hypoaesthesia	3/69 (4.3%)
Motor dysfunction	4/69 (5.8%)
Paraesthesia	1/69 (1.4%)
Peripheral sensory neuropathy	1/69 (1.4%)
Sinus headache	1/69 (1.4%)
Somnolence	2/69 (2.9%)
VIIth nerve paralysis	1/69 (1.4%)
Psychiatric disorders
Anxiety	2/69 (2.9%)
Confusional state	1/69 (1.4%)
Depressed mood	1/69 (1.4%)
Insomnia	7/69 (10.1%)
Libido decreased	1/69 (1.4%)
Mood altered	1/69 (1.4%)
Renal and urinary disorders
Proteinuria	1/69 (1.4%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/69 (1.4%)
Cough	13/69 (18.8%)
Dysphonia	6/69 (8.7%)
Dyspnoea	8/69 (11.6%)
Epistaxis	10/69 (14.5%)
Haemoptysis	4/69 (5.8%)
Hiccups	2/69 (2.9%)
Hypoxia	1/69 (1.4%)
Laryngeal oedema	1/69 (1.4%)
Lung infiltration	1/69 (1.4%)
Nasal congestion	1/69 (1.4%)
Nasal dryness	1/69 (1.4%)
Obstructive airways disorder	2/69 (2.9%)
Oropharyngeal pain	2/69 (2.9%)
Pharyngeal inflammation	1/69 (1.4%)
Pneumothorax	1/69 (1.4%)
Pulmonary haemorrhage	1/69 (1.4%)
Respiratory disorder	1/69 (1.4%)
Rhinalgia	1/69 (1.4%)
Rhinorrhoea	1/69 (1.4%)
Sinus congestion	1/69 (1.4%)
Skin and subcutaneous tissue disorders
Acne	9/69 (13%)
Alopecia	5/69 (7.2%)
Decubitus ulcer	2/69 (2.9%)
Dermatitis acneiform	52/69 (75.4%)
Dry skin	34/69 (49.3%)
Erythema	2/69 (2.9%)
Erythema multiforme	3/69 (4.3%)
Exfoliative rash	17/69 (24.6%)
Granuloma skin	1/69 (1.4%)
Hair colour changes	1/69 (1.4%)
Hair growth abnormal	1/69 (1.4%)
Ingrowing nail	1/69 (1.4%)
Nail bed inflammation	1/69 (1.4%)
Nail disorder	6/69 (8.7%)
Onychomadesis	1/69 (1.4%)
Pain of skin	4/69 (5.8%)
Palmar-plantar erythrodysaesthesia syndrome	24/69 (34.8%)
Photosensitivity reaction	1/69 (1.4%)
Pruritus	20/69 (29%)
Rash	11/69 (15.9%)
Rash erythematous	5/69 (7.2%)
Scab	1/69 (1.4%)
Skin chapped	1/69 (1.4%)
Skin disorder	2/69 (2.9%)
Skin exfoliation	4/69 (5.8%)
Skin fissures	5/69 (7.2%)
Skin hyperpigmentation	2/69 (2.9%)
Skin lesion	2/69 (2.9%)
Telangiectasia	1/69 (1.4%)
Vascular disorders
Flushing	1/69 (1.4%)
Haemorrhage	1/69 (1.4%)
Hypertension	3/69 (4.3%)
Hypotension	1/69 (1.4%)
Intra-abdominal haematoma	1/69 (1.4%)
Lymphoedema	1/69 (1.4%)
Thrombosis	1/69 (1.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.