Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Erlotinib Hydrochloride

Dacomitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

descriptive: non-adenocarcinoma histology

PF-00299804 orally at 45 mg daily, on continuous schedule

PF-00299804

Pfizer CT.gov Call Center

To assess the antitumor efficacy measured by the objective response rate of oral PF-00299804 taken daily, as single agent in patients with advanced NSCLC who failed at least one chemotherapy + erlotinib.

PF-00299804 As A Single Agent, In Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Chemotherapy And Erlotinib

A PHASE 2, OPEN-LABEL, TWO ARM TRIAL TO EVALUATE THE EFFICACY OF PF-00299804 IN PATIENTS WITH ADVANCED NSCLC AFTER FAILURE OF AT LEAST ONE PRIOR CHEMOTHERAPY REGIMEN AND FAILURE OF PRIOR TREATMENT WITH ERLOTINIB

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

BOR:best response recorded from treatment start until disease progression as per Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response: disappearance of all lesions. Partial Response (PR):greater than or equal to (\>=)30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD):\>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease:neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.

BOR: best response recorded from treatment start until disease progression as per RECIST. Complete Response: disappearance of all lesions. PR: \>=30% decrease in SLDs of TLs taking as reference baseline SLD. PD: \>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.

Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

Probability of being event free (event defined as PD or death due to any cause) at 6 months after the first dose of study treatment. PFS was defined as the time from the first dosing date to the date of first documentation of progression or death due to any cause, whichever occurs first. PFS was calculated as (first event date (if not reached, censored at the last known event-free date) minus first dosing date plus 1). Documentation of progression was determined from objective disease assessment based on RECIST v1.0 criteria. PD was defined as at least a 20% increase in the sum of the longest diameters of the target lesions taking as a reference the smallest sum of the longest diameters recorded since treated started or the appearance of 1 or more new lesions.

Probability of being alive at 6 and 12 months after the first dose of study medication.

The pharmacokinetic (PK) samples collected between 22-26 hours post dose on Day 1 of Cycle 1 were within the pre-specified time window for the 24-hour post dose sample and were used for calculation of AUC (0-24) on Day 1 of Cycle 1.

Human epidermal growth factor receptor 2 (HER2) is a transmembrane protein that plays a pivotal role in growth factor signal transduction and epidermal growth factor receptor (EGFR) is a cell surface protein that binds to epidermal growth factor. Levels of the HER-2 and EGFR extracellular domains in serum were assessed by enzyme-linked immunosorbent assay (ELISA).

HER-family is a family of transmembrane protein that plays a pivotal role in growth factor signal transduction and Kirsten Rat Sarcoma (KRAS) gene is an oncogene that encodes a small guanosine triphosphatase (GTPase) transductor protein called KRAS. The mutation status of HER and KRAS genes in tumor DNA present in plasma was determined using a polymerase chain reaction (PCR)-based assay. The gene that is most common in a particular natural population is known as the wild type. Any form of the gene other than the wild type is known as a mutant form. Number of participants with HER-Family and KRAS gene mutation were classified as: wild type, mutant and unknown.

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status (GHS), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.

QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnoea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.

Self-administered questionnaire to measure health-related quality of life (QoL) of adult participants suffering from skin disease; 10 questions concerning participants' perception of impact of their disease over last week encompassing aspects such as symptoms or feelings, daily activities, leisure, work or school, personal relationships and treatment. Questions scored on a 4-point Likert scale: 0 (not relevant), 1 (a little), 2 (a lot), and 3 (very much). Scores of individual questions (0-3) were added to yield a total score (0-30); higher score = greater impairment of participant's QoL.

PFS is defined as time in weeks from randomization to the first documentation of objective tumor progression or death due to any cause. PFS was calculated as = (first event date minus randomization date plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death").

Pfizer

The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Participants with adenocarcinoma histology received PF-00299804 tablet 45 milligram (mg) orally once daily in cycles of 21 days until unacceptable toxicity, tumor progression, death, withdrawal from the study or investigator's discretion.

PF-00299804 (Adenocarcinoma Histology)

Participants with non-adenocarcinoma histology received PF-00299804 tablet 45 mg orally once daily in cycles of 21 days until unacceptable toxicity, tumor progression, death, withdrawal from the study or investigator's discretion.

PF-00299804 (Non-adenocarcinoma Histology)

Total

Age, Continuous

Sex: Female, Male

Results for PK parameters to be assessed using nonlinear mixed effects modelling (NONMEM) are not provided because of change in planned analysis.

Pfizer ClinicalTrials.gov Call Center

Complete response

Partial response

Stable or No response

Objective progression

Indeterminate

Response-evaluable population included all enrolled participants who received at least 1 dose of study treatment, with adequate baseline tumor assessment and at least 1 on-study tumor assessment after the first dosing.

Best Overall Response (BOR) in Participants With Adenocarcinoma Histology

Stable or no response

Best Overall Response (BOR) in Participants With Non-Adenocarcinoma Histology

DR was calculated for the subgroup of participants from the response-evaluable population, with a confirmed objective tumor response (CR or PR).

Duration of Response (DR)

As-enrolled population included all participants who were enrolled in the study.

Percent Probability of Progression-free Survival (PFS) at Month 6

Month 6

Month 12

Percent Probability of Overall Survival at Months 6 and 12

PK concentration population included all enrolled participants who received at least 1 dose of study treatment and had at least 1 measured plasma concentration. Here, 'N' (overall number of participants analyzed) signifies those participants who were evaluable for the measure.

Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)]

PK concentration population included all enrolled participants who received at least 1 dose of study treatment and had at least 1 measured plasma concentration. Here, 'N' signifies those participants who were evaluable for the measure.

Maximum Observed Plasma Concentration (Cmax)

Time to Reach Maximum Observed Plasma Concentration (Tmax)

EGFR: C1D1

EGFR: C2D1

EGFR: C3D1

EGFR: C4D1

EGFR: C5D1

EGFR: C6D1

EGFR: C7D1

EGFR: C8D1

EGFR: C9D1

EGFR: C10D1

HER2: C1D1

HER2: C2D1

HER2: C3D1

HER2: C4D1

HER2: C5D1

HER2: C6D1

HER2: C7D1

HER2: C8D1

HER2: C9D1

HER2: C10D1

The pharmacodynamic population was defined as members of the ITT (as enrolled) population who had baseline samples submitted per Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approval and participant consent. Here, 'number analyzed' signifies participants evaluable at each time point for each arm respectively.

Human Epidermal Growth Factor-2 (HER-2) and Epidermal Growth Factor Receptor (EGFR) Levels in Serum

KRAS mutation: Wild-type

KRAS mutation: Mutant

KRAS mutation: Unknown

HER-2 mutation: Wild-type

HER-2 mutation: Mutant

HER-2 mutation: Unknown

Number of Participants With Human Epidermal Growth Factor Family (HER-Family) and Kirsten Rat Sarcoma (KRAS) Gene Mutation Status From Free Tumor Deoxy- Ribonucleic Acid (DNA) in Blood at Screening

C1D1: GHS

C1D1: Physical functioning

C1D1: Role functioning

C1D1: Emotional Functioning

C1D1: Cognitive Functioning

C1D1: Social Functioning

C1D1: Fatigue

C1D1: Nausea, vomiting

C1D1: Pain

C1D1: Dyspnoea

C1D1: Insomnia

C1D1: Appetite loss

C1D1: Constipation

C1D1: Diarrhea

C1D1: Financial difficulties

C2D1: GHS

C2D1: Physical functioning

C2D1: Role functioning

C2D1: Emotional Functioning

C2D1: Cognitive Functioning

C2D1: Social Functioning

C2D1: Fatigue

C2D1: Nausea, vomiting

C2D1: Pain

C2D1: Dyspnoea

C2D1: Insomnia

C2D1: Appetite loss

C2D1: Constipation

C2D1: Diarrhea

C2D1: Financial difficulties

C3D1: GHS

C3D1: Physical functioning

C3D1: Role functioning

C3D1: Emotional Functioning

C3D1: Cognitive Functioning

C3D1: Social Functioning

C3D1: Fatigue

C3D1: Nausea, vomiting

C3D1: Pain

C3D1: Dyspnoea

C3D1: Insomnia

C3D1: Appetite loss

C3D1: Constipation

C3D1: Diarrhea

C3D1: Financial difficulties

C4D1: GHS

C4D1: Physical functioning

C4D1: Role functioning

C4D1: Emotional Functioning

C4D1: Cognitive Functioning

C4D1: Social Functioning

C4D1: Fatigue

C4D1: Nausea, vomiting

C4D1: Pain

C4D1: Dyspnoea

C4D1: Insomnia

C4D1: Appetite loss

C4D1: Constipation

C4D1: Diarrhea

C4D1: Financial difficulties

C5D1: GHS

C5D1: Physical functioning

C5D1: Role functioning

C5D1: Emotional Functioning

C5D1: Cognitive Functioning

C5D1: Social Functioning

C5D1: Fatigue

C5D1: Nausea, vomiting

C5D1: Pain

C5D1: Dyspnoea

C5D1: Insomnia

C5D1: Appetite loss

C5D1: Constipation

C5D1: Diarrhea

C5D1: Financial difficulties

C6D1: GHS

C6D1: Physical functioning

C6D1: Role functioning

C6D1: Emotional Functioning

C6D1: Cognitive Functioning

C6D1: Social Functioning

C6D1: Fatigue

C6D1: Nausea, vomiting

C6D1: Pain

C6D1: Dyspnoea

C6D1: Insomnia

C6D1: Appetite loss

C6D1: Constipation

C6D1: Diarrhea

C6D1: Financial difficulties

C7D1: GHS

C7D1: Physical functioning

C7D1: Role functioning

C7D1: Emotional Functioning

C7D1: Cognitive Functioning

C7D1: Social Functioning

C7D1: Fatigue

C7D1: Nausea, vomiting

C7D1: Pain

As-enrolled population included all participants who were enrolled in the study. Here, 'N' signifies those participants who were evaluable for the measure and 'number analyzed' signifies participants evaluable at each time point for each arm respectively.

European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score

Spots Global Cancer Trial Database for PF-00299804 As A Single Agent, In Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Chemotherapy And Erlotinib

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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