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PF-00299804 in Stage IIIB or Stage IV Non-Small Cell Lung Cancer Not Responding to Standard Therapy for Advanced or Metastatic Cancer

Phase 3
Completed
Conditions
Lung Cancer
Interventions
Drug: Placebo
Registration Number
NCT01000025
Lead Sponsor
NCIC Clinical Trials Group
Brief Summary

RATIONALE: PF-00299804 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether PF-00299804 is more effective than a placebo in treating patients with advanced non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying PF-00299804 to see how well it works compared with a placebo in treating patients with stage IIIB or stage IV non-small cell lung cancer that has not responded to standard therapy for advanced or metastatic cancer.

Detailed Description

OBJECTIVES:

Primary

* To compare overall survival in patients with incurable stage III or IV non-small cell lung cancer receiving PF-00299804 versus placebo after failure of standard therapy for advanced metastatic disease.

Secondary

* To compare overall survival in KRAS-WT patients between the two arms.

* To compare overall survival in EGFR-mutant patients between the two arms.

* To compare progression-free survival between arms.

* To compare objective response rates between arms.

* To estimate time to response and response duration in these patients.

* To evaluate the nature, severity, and frequency of toxicities between arms.

* To compare quality of life between arms.

* To determine the incremental cost-effectiveness and cost-utility ratios for PF-00299804.

* To correlate the expression of tumor and blood markers (at diagnosis) with outcomes and response.

OUTLINE: This is a multicenter study. Patients are stratified according to center, performance status (0 or 1 vs 2 or 3), tobacco use (never vs past or present), best response to prior EGFR tyrosine kinase inhibitor (progressive disease vs other), weight loss (\< 5% vs ≥ 5% or unknown), and ethnicity (East Asian vs other). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Blood, serum, plasma, and tissue samples are collected and examined for biomarkers and gene mutations, and may be banked for future studies.

Patients complete quality-of-life questionnaires EORTC QLQ-C30 and other questionnaires at baseline and then periodically during and after completion of study treatment.

Cost effectiveness and cost utility of PF-00299804 is assessed via the Health Utilities Index (EQ-5D) and the Resource Utilization Assessment periodically.

After completion of study treatment, patients are followed at 4 weeks and then every 12 weeks thereafter.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
720
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PF-00299804PF-00299804Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
PlaceboPlaceboPatients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Overall Survival42 Months

Median and 95% confidence intervals

Secondary Outcome Measures
NameTimeMethod
Overall Survival in EGFR-mutant Patients42 Months

Overall survival by EGFR-mutantion subgroups

Overall Survival in KRAS-WT Patients42 Months

Median and 95% confidence intervals of Overall survival in KRAS-WT patients

Objective Response Rate42 months

Response were evaluated in this study using the revised international criteria (1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumours) committee. BEST RESPONSE from the start of study treatment until the end of treatment were reported.Objective response rate is the sum of CR + PR divided by the total number of patients in each group.

Number of Participants With Toxicity as Measured by NCI CTCAE Version 4.042 Months

Number of participants with Toxicities by treatment received according to NCI CTCAE version 4.0

Progression-free Survival42 Months

progression were evaluated using the revised international criteria (1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumours) committee

Trial Locations

Locations (88)

Chonnan National University Hwasun Hospital

🇰🇷

Jeongnam, Korea, Republic of

CER - Instituto Medico

🇦🇷

Buenos Aires, B1878dvb Bs. As., Argentina

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

COIBA Centro de Oncologia e Investigacion

🇦🇷

Berazategui, Provincia De Buenos Aires, Argentina

Frankston Hospital - Peninsula Oncology Centre

🇦🇺

Frankston, Victoria, Australia

Monash Medical Centre

🇦🇺

Clayton, Victoria, Australia

Austin Hospital

🇦🇺

Heidelberg, Victoria, Australia

BCCA - Fraser Valley Cancer Centre

🇨🇦

Surrey, British Columbia, Canada

QEII Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

Dr. H. Bliss Murphy Cancer Centre

🇨🇦

St. John's, Newfoundland and Labrador, Canada

Hospital Central De La Fuerza Aerea Del Peru

🇵🇪

Lima, Peru

Perpetual Succour Hospital

🇵🇭

Cebu City, Philippines

Damic-Fundacion Rusculleda

🇦🇷

Cordoba, Argentina

Chi-Mei Foundation Hospital

🇨🇳

Tainan, Taiwan

Phillippine General Hospital

🇵🇭

Manila, Philippines

Tri-Service General Hospital

🇨🇳

Taipei, Taiwan

Makati Medical Center

🇵🇭

Makati City, Philippines

China Medical University Hospital

🇨🇳

Taichung, Taiwan

Ramathibodi Hospital

🇹🇭

Bangkok, Thailand

Siriraj Hospital, Oncology Unit

🇹🇭

Bangkok, Thailand

Maharaj Nakorn Chiangmai Hospital

🇹🇭

Chiangmai, Thailand

Chulalongkorn University

🇹🇭

Bangkok, Thailand

Royal Prince Alfred Hospital

🇦🇺

Camperdown, New South Wales, Australia

Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

Allan Blair Cancer Centre

🇨🇦

Regina, Saskatchewan, Canada

Ospedale San Raffaele

🇮🇹

Milan, Italy

U.O.C. di Oncologia U.L.S.S. 13

🇮🇹

Mirano, Italy

Policlinico Umberto I, Universita Sapienza

🇮🇹

Rome, Italy

Sir Charles Gairdner Hospital

🇦🇺

Perth, Western Australia, Australia

CHUM - Hopital Notre-Dame

🇨🇦

Montreal, Quebec, Canada

Saskatoon Cancer Centre

🇨🇦

Saskatoon, Saskatchewan, Canada

Western Hospital

🇦🇺

Footscray, Victoria, Australia

Intstituto Scientifico Romangnolo

🇮🇹

Meldola, Italy

Shapiro, Stafford and Yee

🇺🇸

Arcadia, California, United States

Clintell, Inc.

🇺🇸

Skokie, Illinois, United States

Centro Medico San Roque

🇦🇷

San Miguel de Tucuman, Argentina

Concord Repatriation General Hospital

🇦🇺

Concord, New South Wales, Australia

St. George Hospital, Cancer Care Centre

🇦🇺

Kogarah, New South Wales, Australia

Prince of Wales Hospital

🇦🇺

Randwick, New South Wales, Australia

Royal North Shore Hospital

🇦🇺

St. Leonards, New South Wales, Australia

Calvary Mater Newcastle Hospital

🇦🇺

Waratah, New South Wales, Australia

Nambour General Hospital

🇦🇺

Nambour, Queensland, Australia

Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

The Prince Charles Hospital

🇦🇺

Chermside, Queensland, Australia

Geelong Hospital

🇦🇺

Geelong, Victoria, Australia

Centro de Oncologia e Radioterapia (COR) Mae de Deus

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

ESHO - Empresa de Servicos Hospitalares Ltda.

🇧🇷

Brasilia, Sao Paulo, Brazil

Fundacao Pio XII - Hospital de Cancer de Barretos

🇧🇷

Barretos, SP, Brazil

Oxion Hospital Dia Oncologia LTDA - Oxion

🇧🇷

Belo Horizonte, Brazil

Centro de Pesquisa Clinica do Hospital

🇧🇷

Porto Alegre, SP, Brazil

Nucleo de Oncologia da Bahia

🇧🇷

Salvador, Brazil

BCCA - Abbotsford Centre

🇨🇦

Abbotsford, British Columbia, Canada

GRAM - Grupo de Assistencia Medica

🇧🇷

Sao Paulo, Brazil

Atlantic Health Sciences Corporation

🇨🇦

Saint John, New Brunswick, Canada

Cancer Centre of Southeastern Ontario at Kingston

🇨🇦

Kingston, Ontario, Canada

London Regional Cancer Program

🇨🇦

London, Ontario, Canada

Lakeridge Health Oshawa

🇨🇦

Oshawa, Ontario, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

🇨🇦

Hamilton, Ontario, Canada

Ottawa Health Research Institute - General Division

🇨🇦

Ottawa, Ontario, Canada

Algoma District Cancer Program

🇨🇦

Sault Ste. Marie, Ontario, Canada

Health Sciences North

🇨🇦

Sudbury, Ontario, Canada

Niagara Health System

🇨🇦

St. Catharines, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

🇨🇦

Windsor, Ontario, Canada

McGill University - Dept. Oncology

🇨🇦

Montreal, Quebec, Canada

A.O. Busto Arsizio - P.O. Saronno

🇮🇹

Saronno, VA, Italy

Centro di Riferimento Oncologico - CRO

🇮🇹

Aviano, PN, Italy

U.O. di Oncologia Medica Azienda Ospedaliera G Rummo

🇮🇹

Benevento, Italy

Ospedale Santa Croce

🇮🇹

Fano, Italy

U.O. di Oncologia Ospedale Villa Scassi

🇮🇹

Genova, Italy

U.O.C. Terapie Integrate in Oncologia,

🇮🇹

Messina, Italy

U.O.C. Oncologia Medica,

🇮🇹

Messina, Italy

Dott. Fortunato Ciardiello,Cattedra Oncologia Medica

🇮🇹

Napoli, Italy

La Maddalena, Dipartimento Oncologico

🇮🇹

Palermo, Italy

Unita Sperimentazioni Cliniche Istituto per lo

🇮🇹

Napoli, Italy

UOC Oncologia Medica II Instituto Oncologio Veneto

🇮🇹

Padova, Italy

Azienda USL di Piacenza, Ospedale Gugliemimo Salieto

🇮🇹

Piacenza, Italy

Azienda Ospedaliera S. Camillo-Forlanin

🇮🇹

Rome, Italy

Ospedale Casa Sollievo della Sofferenza

🇮🇹

San Giovanni Rotondo, Italy

Ospedale E. Morelli-Sondalo

🇮🇹

Sondalo, Italy

Ajou University Hospital

🇰🇷

GyeongGi-Do, Korea, Republic of

Yonsei University College of Medicine

🇰🇷

Seoul, Korea, Republic of

Seoul Veterans Hospital

🇰🇷

Seoul, Korea, Republic of

Auckland City Hospital

🇳🇿

Auckland, New Zealand

Hospital Nacional Luis N. Saenz

🇵🇪

Lima, Peru

Instituto de Oncologia y Radioterapia de

🇵🇪

Lima, Peru

The Catholic University of Korea,

🇰🇷

Seoul, Korea, Republic of

BCCA - Vancouver Cancer Centre

🇨🇦

Vancouver, British Columbia, Canada

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