A Randomized Trial Of PF-00299804 Taken Orally Versus Erlotinib Taken Orally For Treatment Of Advanced Non-Small Cell Lung Cancer That Has Progressed After One Or Two Prior Chemotherapy Regimen

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Randomized Phase 2 Trial Of Pf-00299804 Versus Erlotinib For The Treatment Of Advanced Non-small Cell Lung Cancer After Failure Of At Least One Prior Chemotherapy Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00769067
• Other study ID #: A7471028
• Secondary ID: 2008-005235-14
• Status: Completed
• Phase: Phase 2
• First received: October 7, 2008
• Last updated: September 22, 2015
• Start date: November 2008
• Est. completion date: August 2014

Study information

• Verified date: September 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will compare PF-00299804 given orally on continuous schedule to the approved drug, erlotinib, in patients whose non-small cell lung cancer has progressed after chemotherapy; patients will be randomized to receive one of these drugs, and followed for efficacy and tolerance of each.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: August 2014
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• advanced measurable Non-Small Cell Lung Cancer (NSCLC);

• progressed after 1-2 prior chemotherapy;

• Eastern Cooperative Oncology Group (ECOG) 0-2;

• tissue available for future KRAS/ EGFR testing

Exclusion Criteria:

• prior Epidermal Growth Factor Receptor (EGFR) targeted therapy;

• active or untreated Central Nervous System (CNS) metastases;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Erlotinib
Continuous oral dosing at 150 mg daily.
• PF-00299804
Continuous oral dosing at 45mg daily

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	St. Vincent's Hospital	Fitzroy	Victoria
Australia	The Andrew Love Cancer Centre,	Geelong	Victoria
Australia	Border Medical Oncology	Wodonga	Victoria
Brazil	FUNDACAO PIO XII Hospital de Cancer de Barretos	Barretos	SP
Brazil	Hospital Sao Lucas da PUCRS	Porto Alegre	RS
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre (ISCMPA) - Hospital Santa Rita	Porto Alegre	RS
Brazil	Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira - ICESP	Sao Paulo	SP
Canada	Royal Victoria Hospital	Barrie	Ontario
Canada	RSM Durham Regional Cancer Centre - Lakeridge Health Oshawa	Oshawa	Ontario
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	BC Cancer Agency - Vancouver Centre	Vancouver	British Columbia
Hong Kong	Department of Clinical Oncology	Shatin	New Territories
Hong Kong	Department of Clinical Oncology, Tuen Mun Hospital	Tuen Mun	New Territories
Korea, Republic of	SamsungMedicalCenter,SungkyunkwanUnivSchoolofMedicine,Div. of Hematology-Oncology, Dep. of Medicine	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University College of Medicine, Yonsei Cancer Center	Seoul
Poland	Medex spolka cywilna	Chrzanow
Poland	"Vesalius" Sp. z o.o.	Krakow
Poland	¿KardioDent¿	Krakow
Poland	Zaklad Rentgena i USG Wyrobek spolka jawna	Krakow
Poland	Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie	Warsaw
Poland	Niepubliczny Zaklad Opieki Zdrowotnej AVI Centrum Medyczne	Warszawa
Puerto Rico	Ponce School of Medicine / CAIMED Center	Ponce
Singapore	National Cancer Centre	Singapore
Spain	Hospital Universitari Germans Trias I Pujol	Badalona	Barcelona
Spain	Hospital de Cruces	Barakaldo	Vizcaya
Spain	Hospital Teresa Herrera	La Coruña
Spain	Hospital Son Llatzer	Palma de Mallorca	Islas Baleares
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital, Chest Department	Taipei
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester
United Kingdom	Churchill Hospital	Oxford
United States	Winship Cancer Institute at Emory University	Atlanta	Georgia
United States	Winship Cancer Institute at Grady Health Systems	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Augusta Oncology Associates, P.C.	Augusta	Georgia
United States	Augusta Oncology Associates, PC	Augusta	Georgia
United States	Center for Blood and Cancer Disorders	Bethesda	Maryland
United States	Bridgeport Hospital	Bridgeport	Connecticut
United States	Oncology/Hematology Associates	Clarksburg	West Virginia
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Georgia Cancer Specialists	Decatur	Georgia
United States	The Longstreet Cancer Center	Gainesville	Georgia
United States	Central Georgia Cancer Care, P.C.	Macon	Georgia
United States	Northwest Georgia Oncology Center	Marietta	Georgia
United States	The West Clinic	Memphis	Tennessee
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Agajanian Institute of Oncology and Hematology	Montebello	California
United States	Northwest Alabama Cancer Center	Muscle Shoals	Alabama
United States	Wittingham Cancer Center @ Norwalk Hospital	Norwalk	Connecticut
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Kootenai Cancer Center at Post Falls	Post Falls	Idaho
United States	Associates in Oncology/Hematology, PC	Rockville	Maryland
United States	Central Georgia Cancer Care, P.C.	Warner Robins	Georgia
United States	Medical Oncology & Hematology, P.C.	Waterbury	Connecticut
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Hong Kong,  Korea, Republic of,  Poland,  Puerto Rico,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation	Tumor tissue were analyzed at a sponsor-designated laboratory to investigate KRAS and EGFR status (wild type or mutated). Participants who did not provide samples for central laboratory analysis confirmation were classified as "unknown". Additionally blood specimens were analyzed at a sponsor-designated laboratory for T790M mutation in EGFR.	Baseline	No
Other	Soluble Protein Biomarkers Level	Blood specimens were analyzed at a sponsor-designated laboratory for analysis of shed proteins/receptors related to Human Epidermal Growth Factor Receptor (HER) signaling (EGFR, HER-2, Epithelial-cadherin [E-cadherin]). The data collection after C12D1 was not performed, as there were too few participants across both treatment arms after C12D1.	Cycle (C) 1 Day (D) 1 (baseline), D1 of each subsequent cycle up to end of treatment (up to 121 weeks)	No
Other	Trough Plasma Concentration (Ctrough) of Dacomitinib (PF-00299804)	Only participants from "Dacomitinib" treatment arm were planned to be analyzed for this outcome.	C1D10-14, C2D1, C3D1, C4D1	No
Primary	Progression-Free Survival (PFS)	PFS: Time in weeks from randomization to date of objective disease progression or death due to any cause, whichever occurred first. PFS was calculated as (first event date or last known event-free date [if the event date unavailable] minus the date of randomization plus 1) divided by 7. Objective progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LDs) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.	Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks	No
Secondary	Categorical Summary of Overall Scale Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	EORTC QLQ-C30: included global health status/quality of life (QoL), functional (Fn) scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Scores were averaged, transformed to 0-100 scale; higher score for Global Qol/Fn scales=better level of QoL/functioning or higher score for symptom scales/items=greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline: for Global QoL/Fn scales >=10; for symptom scale/item <=-10), Worsened (if average scales change from baseline: for Global QoL/Fn scales <=-10; for symptom scale/item >=10), and Stable (if average scales change from baseline >-10 but <10 for Global QoL/Fn scales and symptom scale/item) and participants in each category are reported.	Baseline up to Cycle 44 (Week 188)	No
Secondary	Categorical Summary of Overall Scale Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13)	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 dyspnea 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). Scores averaged, transformed to 0-100 scale; higher symptom score = greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline <=-10), Worsened (if average scales change from baseline >=10), and Stable (if average scales change from baseline >-10 but <10) and participants in each category are reported.	Baseline up to Cycle 44 (Week 188)	No
Secondary	Dermatology Life Quality Index (DLQI)	DLQI: 10-item questionnaire to measure how much the participant's skin problem has impacted their life over the previous week on following 6 domains: symptoms/feelings (2 questions), daily activities (2 questions), leisure (2 questions), work/school (1 question), personal relationships (2 questions), and treatment (1 question). All questions were answered on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much/prevented work or studying). The DLQI total evaluable score was calculated by summing the score of each question and ranged from 0 to 30, where higher scores indicated more quality of life impairment.	Cycle (C) 1 Day (D) 1 (baseline), C1D10-14, D1 of subsequent cycles up to C44	No
Secondary	Percentage of Participants With Objective Response	Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0. CR: disappearance of all target and non-target lesions. PR: at least 30 % decrease in sum of the LDs of target lesion, taking as reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.	Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks	No
Secondary	Best Overall Response (BOR)	Number of participants with BOR according to RECIST version 1.0: CR= disappearance of all target and non-target lesions. PR= at least 30% decrease in sum of LDs of target lesion, taking as reference baseline sum LD. Stable/no response= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LDs since treatment started. Objective progression= at least a 20% increase in sum of LDs of target lesions, taking as reference the smallest sum of LDs recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.	Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks	No
Secondary	Duration of Response (DR)	Time in weeks from first documentation of objective tumor response to objective tumor progression or symptomatic deterioration or death due to any cause, whichever occurred first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or symptomatic deterioration or death due to any cause or last known progression-free date [if none of the event dates available] minus the date of the first CR or PR [which ever occurred first] that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.	Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks	No
Secondary	Overall Survival (OS)	Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date or last known alive date (if death date unavailable) minus the date of randomization plus 1) divided by 7.	Baseline until end of treatment (15 August 2014); followed up every 8 weeks after discontinuation from study treatment.	No