Non-Small Cell Lung Cancer MedDRA version: 14.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Product Name: Dacomitinib
Product Code: PF-00299804
Pharmaceutical Form: Tablet
INN or Proposed INN: Dacomitinib
Current Sponsor code: P
Sponsors
SFJ LungCancer, Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of a voluntarily given, personally signed and dated, written informed consent document; 2. Age ?20 years in Japan and Korea, and ?18 years in other countries, male or female; 3. The presence of EGFR activating mutation (exon 19 deletion or the L858R mutation in exon 21) confirmed by the local laboratory based on the Qiagen - Therascreen® EGFR Mutation Detection Kit RGQ (Scorpions ARMS) in ex-China, or similar test methods approved by the sponsor. It is acceptable for subjects with the presence of the exon 20 T790M mutation together with either EGFR activating mutation (exon 19 deletion or the L858R mutation in exon 21) to be included in this study; 4. Evidence of stage IIIB/IV (based on Union for International Cancer Control (UICC) staging system version 77) NSCLC of adenocarcinoma histology or its pathologically accepted variants (assessed by a local laboratory in ex-China, by a central laboratory in China). For this purpose the World Health Organization/International Association of Study of Lung Cancer Histologic Classification of Lung Cancer Criteria will be used and the diagnosis of NSCLC NOS (not otherwise specified), squamous or mixed adeno-squamous lung carcinomas will not be allowed; 5. Tissue must be available for central laboratory confirmation of adenocarcinoma histology and activating mutation (unstained 4-6 slides from formalin fixed paraffin embedded block or a formalin fixed paraffin embedded block is required); 6. Have an ECOG PS of 0 or 1; 7. No prior treatment with systemic therapy for NSCLC; 8. Radiologically measurable disease by RECIST v1.1 criteria: a. At least one target lesion that has not previously been radiated, and is measurable according to RECIST v1.1; b. Acceptable radiologic procedures for disease assessment include contrast enhanced conventional or spiral computed tomography (CT), or magnetic resonance imaging (MRI); contrast enhanced scans are required in the absence of contrast-allergy and subject intolerance of MRI. The following are not allowed as sole documentation of target lesions: CT component of positron emission tomography (PET)/CT, ultrasound alone, nuclear scans (including bone or PET scans), chest X-ray or bone radiographs, and tumor markers; 9. Adequate organ function, including: a. Estimated creatinine clearance ?30 mL/min (as determined by Cockcroft-Gault formula or the study site?s standard formula); b. Urinary protein <3+ by urine dipstick. If urine protein by dipstick is ?3+, then a urine protein/creatinine ratio (UPC) should be obtained. The subject may enter only if UPC is <2.0; c. Absolute neutrophil count (ANC) ?1500 cells/mm3; d. Platelets ?100,000 cells/mm3; e. Hemoglobin ?10.0 g/dL; f. Bilirubin ? 1.5 x ULN; g. AST (also known as SGOT) and ALT (also known as SGPT) ?2.5 x ULN (?5.0 x ULN if hepatic metastases). 10. Female subjects must be postmenopausal (defined as 12 months of amenorrhea following last menses), or they or their partners must be surgically sterile, or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the investigator
Exclusion criteria
Exclusion criteria: 1. Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer. Variations of adenocarcinoma are allowed, however no squamous element can be present; 2. Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation; 3. Any history of brain metastases or leptomeningeal metastases, even if treated with radiation or surgery in the past and now stable; 4. Any previous anti-cancer systemic treatment of early, locally advanced, or metastatic NSCLC including but not limited to chemotherapy, targeted therapies, small molecules, EGFR-TKIs and other tyrosine-kinase-inhibitors, monoclonal antibodies, anti-cancer vaccines, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, i.e., non target lesions); 5. Any surgery (not including minor procedures such as lymph node biopsy), palliative radiotherapy or pleurodesis within 2 weeks of baseline assessments; 6. Any clinically significant gastrointestinal abnormalities that may impair intake, transit or absorption of the study drug, such as the inability to take oral medication; 7. Current enrollment in another therapeutic clinical study, or use of a product with known effects on metabolism of the study drugs within 4 weeks of baseline assessments; 8. Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this study; or known drug abuse/alcohol abuse; 9. History of, or currently suspected, diffuse non-infectious pneumonitis or interstitial lung disease including: a. Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease; b. Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at baseline; c. Insufficient lung function as determined by either clinical examination or an arterial oxygen tension of <70 Torr. 10. Any history of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption 11. Uncontrolled or significant cardiovascular disease, including: a. Myocardial infarction within the last 12 months; b. Uncontrolled angina within the last 6 months; c. Congestive heart failure within the last 6 months; d. Diagnosed or suspected congenital long QT syndrome; e. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); f. Prolonged QTc interval on ECG; QTc must be less than CTCAE v4.0 Grade 2 (?480 msec) using Fridericia?s or Bazett?s correction formula with a manual reading by the investigator if required. The ECG may be repeated for evaluation of eligibility after management of correctable causes for observed QTc prolongation; g. Any history of second or third degree heart block; h. Heart rate <50 beats per minute on ECG in the presence of clinical symptoms (e.g., hypotension, evidence of hypoperfusion); i. Uncont
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that dacomitinib treatment is superior to gefitinib treatment with respect to Progression-Free Survival (PFS) as determined by blinded independent radiologic central (IRC) review, in the study population.;Primary end point(s): Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by blinded IRC review.;Timepoint(s) of evaluation of this end point: Evaluated at the end of Cycle 1 and Cycle 2, then every other cycle (within 7 days of the start of subsequent cycle including Day 1 of subsequent cycle),; Secondary Objective: ? To compare secondary measures of efficacy: Overall Survival (OS), PFS, Objective Response Rate (ORR) and Duration of Response (DR) ? To evaluate the safety and tolerability between the two treatment arms; ? To compare the Patient Reported Outcomes (PRO) of health-related quality of life (HRQOL), and disease/treatment-related symptoms between the two arms; ? To compare the PRO of health status between the two arms; ? To explore the relative effect of treatment between the two treatment arms on tumors harboring exon 19 deletion and the L858R mutation in exon 21; ? To characterize the multiple-dose PK of dacomitinib and its major circulating metabolite PF-05199265 in Chinese subjects currently residing in mainland China, who were born in China, and whose parents are both Chinese descent (Arm A only); ? To determine dacomitinib and its major circulating metabolite PF-05199265 trough concentrations (Ctrough) for the evaluation of steady-state PK (Arm A only, at selected sites). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Overall Survival (OS) and OS at 30 months (OS30m); ? PFS as determined by investigator assessment (INV); ? Best Overall Response (BOR) as determined by both IRC and INV assessments; ? Duration of Response (DR) as determined by both IRC and INV assessments; ? Overall safety profile: adverse events (AEs) and laboratory abnormalities by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0, and left ventricular ejection fraction (LVEF); ? Patient Reported Outcomes (PRO) of health related quality of life (HRQOL), and disease/treatment-related symptoms between the two arms as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30), its Lung Cancer module (QLQ-LC13); ? Patient Reported Outcomes (PRO) of health status between the two arms as measured by the EuroQol 5 Dimension (EQ-5D); ? Multiple dose PK parameter estimates of dacomitinib and its major circulating metabolite PF-05199265 in Chinese subjects currently residing in mainland China, who were born in China, and whose parents are both Chinese descent (Arm A only); ? Trough concentrations (Ctrough) of dacomitinib and its major circulating metabolite PF-05199265, as determined from trough plasma samples (Arm A only, at selected sites). ;Timepoint(s) of evaluation of this end point: Evaluated throughout the treatment phase | — |
Countries
China, Hong Kong, Italy, Japan, Korea, Democratic People's Republic of, Poland, Spain, Taiwan
Contacts
Public ContactWRS Oncology Europe
Pfizer Italia S.r.l.
Outcome results
None listed