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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Carcinoma, Non Small Cell Lung

Intervention / Treatment
-----------------
* Drug: PF-00299804
* Drug: PF-00299804


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Advanced Non-Small Cell Lung Cancer (NSCLC) Prior treatment with and failure of at least one regimen of chemotherapy and erlotinib. Prior treatment with no more than two chemotherapy regimens, including adjuvant or combined modality treatment. Measurable disease . Eastern Cooperative Oncology Group (ECOG) Performance status 0-2 Tissue available for KRAS/ EGFR testing Creatinine clearance > 40 cc/min or serum creat < 1.5 x ULN Exclusion Criteria: Chemotherapy Radiotherapy Biological or investigational agents within 4 weeks of baseline disease assessment. Patients who lack of tolerance of erlotinib therapy.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>descriptive: adenocarcinoma histology | Drug: PF-00299804<br>* PF-00299804 orally at 45 mg daily, on continuous schedule<br>|
| Experimental: 2<br>descriptive: non-adenocarcinoma histology | Drug: PF-00299804<br>* PF-00299804 orally at 45 mg daily, on continuous schedule<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) in Participants With Adenocarcinoma Histology | 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. | Baseline, end of every even-numbered cycle up to end of treatment (Day 936) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) in Participants With Non-Adenocarcinoma Histology | 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. | Baseline, end of every even-numbered cycle up to end of treatment (Day 936) | 
| Duration of Response (DR) | 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. | Baseline, end of every even-numbered cycle up to end of treatment (Day 936) | 
| Percent Probability of Progression-free Survival (PFS) at Month 6 | 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. | Up to 6 months after the start of study medication | 
| Percent Probability of Overall Survival at Months 6 and 12 | Probability of being alive at 6 and 12 months after the first dose of study medication. | Months 6, 12 | 
| Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] | 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. | 0.5-2, 3-5, 6-8, 22-26 hours post dose on Day 1 of Cycle 1 | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0.5-2, 3-5, 6-8, 22-26 hours post dose on Day 1 of Cycle 1 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0.5-2, 3-5, 6-8, 22-26 hours post dose on Day 1 of Cycle 1 | 
| Human Epidermal Growth Factor-2 (HER-2) and Epidermal Growth Factor Receptor (EGFR) Levels in Serum | 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). | Baseline [pre-dose on Cycle 1 Day 1 (C1D1)], then pre-dose on Day 1 of each cycle, end of treatment (Day 936) | 
| 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 | 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. | Screening | 
| European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score | 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. | Baseline (C1D1), C2D1 thereafter every subsequent cycle up to C43 | 
| European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Lung Cancer-13 (QLQ- LC13) Score | 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. | Baseline (C1D1), C2D1 thereafter every subsequent cycle up to C43 | 
| Dermatology Life Quality Index (DLQI) Score | 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. | Baseline (C1D1), C2D1 thereafter every subsequent cycle up to C43 | 
| Percentage of Participants With Progression-free Survival (PFS) | 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). | Month 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
non-small cell lung cancer, advanced, previously treated