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

NCT01000025 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: BR26CAN-NCIC-BR26PFIZER-CAN-NCIC-BR26CDR0000657246
• Study Type: interventional
• Target: 720
• Locations: 12 countries
• Sites: 89

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.

Conditions

Lung Cancer

Keywords

stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Median and 95% confidence intervals

  42 Months

Secondary Outcomes (5)

• Overall Survival in KRAS-WT Patients

  42 Months

• Overall Survival in EGFR-mutant Patients

  42 Months

• Progression-free Survival

  42 Months

• Objective Response Rate

  42 months

• Number of Participants With Toxicity as Measured by NCI CTCAE Version 4.0

  42 Months

Study Arms (2)

PF-00299804

ACTIVE COMPARATOR

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

Drug: PF-00299804

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

PF-00299804 DRUG

PF-804 45 mg PO, daily

PF-00299804

Placebo DRUG

Placebo 45 mg PO, daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Eligibility Criteria * Histologically confirmed diagnosis of non-small cell carcinoma of the lung. Patients must have an adequate histopathology or cytology specimen must consent to release of all specimens for this protocol, and the centre/pathologist must have agreed to submission of the specimens. * Patients must have evidence of disease, but measurable disease is not mandatory. To be considered evaluable for complete or partial response assessment, patients must have at least one measurable lesion as follows: X-ray ≥ 20 mm Spiral CT scan or physical exam ≥ 10 mm (lymph nodes must be ≥ 15 mm in the short axis); Measurable lesions must be outside a previous radiotherapy field if they are the sole site of disease, unless disease progression has been documented. * Male or female, 18 years of age or older. * ECOG performance status of 0, 1, 2 or 3. Patients with performance status of 3 are eligible providing that the investigator attests that the patient has a reasonable life expectancy (≥ 6 weeks). * Adequate renal and hepatic functions as defined by the following required laboratory values obtained within 14 days prior to randomization. If anemic, patients should be asymptomatic and should not be decompensated. Creatinine \<1.5 upper limit of normal Total bilirubin \< 1.5 upper limit of normal ALT (SGPT) \< 2.5 times the upper limit of normal. Note: If clearly attributable to liver metastasis, ALT (SGPT) values \< 5 times the upper limit of normal are permitted. \- Previous Therapy Failure of a treatment regimen is defined as the inability to continue a regimen for any reason including, but not limited to, progressive disease, toxicity, or patient request. Up to a maximum of three lines of chemotherapy for advanced/metastatic disease (defined below) and at least one of erlotinib or gefitinib for advanced/ metastatic disease (defined below) should have failed. Exchange of one chemotherapy agent for another within a combination chemotherapy regimen is not considered a new regimen in the following circumstances * carboplatin is substituted for cisplatin due to nephrotoxicity * one agent in the combination regimen is changed due to hypersensitivity occurring in the first cycle. Chemotherapy for Advanced/Metastatic Disease: Patients must have recovered from any reversible toxic effects and at least 21 days must have elapsed from the last dose and prior to randomization (14 days from the last dose for chemotherapy regimens administered on a weekly schedule). Further palliative cytotoxic chemotherapy must not be planned. Patients \< 70 years: • Must have received 1 and up to a maximum of 3prior chemotherapy regimens (at least one of the three must have been a combination regimen and at least one must have contained platinum). Patients ≥ 70 years (generally accepted as being at the time of the administration of the first regimen of chemotherapy for advanced disease): • Must have received 1 and up to a maximum of 3 prior chemotherapy regimens for their disease. These may have been single agent chemotherapy regimens and a platinum agent is not required in keeping with current standards of practice. Adjuvant Chemotherapy: Patients may ALSO have had prior adjuvant therapy for completely resected disease, providing completed at least 12 months prior to randomization. Adjuvant regimens \< 12 months prior to randomization and combined chemotherapy/radiation regimens for irresectable locally advanced stage III disease (irrespective of timing), are considered to be for advanced/metastatic disease and constitute one of the 3 permissible regimens. Patients must have recovered from any reversible treatment related toxicities prior to randomization. EGFR Inhibitor Therapy: Patients may only be enrolled after failure of prior gefitinib or erlotinib for advanced or metastatic disease. Patients who have received adjuvant gefitinib or erlotinib for completely resected NSCLC and who have recurred \< 12 months after discontinuing erlotinib or gefitinib are eligible. Patients who received gefitinib or erlotinib for neoadjuvant therapy only are not eligible. EGFR inhibitor therapy must have been discontinued at least 21 days prior to randomization. Patients who discontinued prior gefitinib or erlotinib therapy for severe or life threatening organ toxicity are not eligible. Patients may also have received other EGFR active agents (such as reversible oral agents or monoclonal antibodies or vaccines) in addition to erlotinib or gefitinib but may not have received ANY prior irreversible EGFR inhibitor such as BIBW2992, HKI-272 (neratinib). Maintenance Therapy: The same chemotherapy or agent/s continued for longer than 4-6 cycles for the purposes of 'maintenance' is considered one regimen; if another chemotherapy agent is given with 'maintenance' intent, it is considered a second regimen providing that 'failure' is documented. Patients who received erlotinib or gefitinib with 'maintenance' intent after completion of 1st line chemotherapy are eligible providing that 'failure' is documented. Radiation: Patients may have had prior radiation therapy provided that a minimum of 14 days has elapsed between the end of radiotherapy and randomization onto the study. (Exceptions may be made however, for low dose, non-myelosuppressive radiotherapy. Patients must have recovered from any acute toxic effects from radiation prior to randomization. Previous Surgery: Previous surgery is permitted provided that wound healing has occurred and at least 14 days have elapsed (major surgery). * Patient able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires. The baseline assessment must already have been completed. Inability (illiteracy, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible. * Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. * Patients must be accessible for treatment and follow-up. All randomized patients must be followed and treated at participating centres. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up. * In accordance with NCIC CTG policy, protocol treatment is to begin within 2 working days of patient randomization. Ineligibility Criteria Patients who fulfill any of the following criteria are not eligible for admission to the study: * Patients receiving concurrent treatment with other experimental drugs or anti-cancer therapy. * Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, should have a LVEF \> 50%. * Patients with untreated brain or meningeal metastases are not eligible (CT scans are not required to rule this out unless there is a clinical suspicion of CNS disease). Patients with treated CNS disease who have radiologic or clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to randomization). * Patients with active or uncontrolled infections, or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol, including * Severe dry eye syndrome * Keratoconjunctivitis sicca * Sjogren's syndrome * Severe exposure keratopathy * Disorders that might increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis) * Uncontrolled inflammatory gastrointestinal diseases (Crohn's, ulcerative colitis etc.) * Prior pneumonitis/ILD secondary to EGFR inhibitors * Mean QTc with Bazetts correction \> 470msec in screening ECG or history of familial long QT syndrome. * Drugs that are highly dependent on CYP2D6 for metabolism are prohibited, since PF-804 is a potent CYP2D6 inhibitor in in vitro assays. These inhibitors or inducers are prohibited from 7 days prior to the first dose until the end of treatment with PF-804. These include: S-metoprolol, propafenone, timolol, amitriptyline, clomipramine, desipramine, imipramine, paroxetine, haloperidol, risperidone, thioridazine, codeine, flecainide, mexilletine, tamoxifen, venlafaxine. Lidocaine may be used with clinical monitoring (including telemetry). Opiates such as morphine, oxycodone, dihydrocodeine, hydrocodone, and tramadol can be used as substitutes to replace codeine. Use of these opiates should be monitored for altered analgesia during treatment with PF-804 as they may be partly metabolized by CYP2D6. If PF-804 is administered with drugs which are P-glycoprotein (P-gp) substrates and have a narrow therapeutic index, monitoring for exaggerated effect and/or toxicities is recommended. * Pregnancy or inadequate contraception. Women must be post-menopausal, surgically sterile, or use two reliable forms of contraception. Women of child-bearing potential must have a pregnancy test taken and proven negative within 7 days prior to randomization. Men must be surgically sterile or use a barrier method of contraception.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• Pfizer: collaborator

Study Sites (89)

Shapiro, Stafford and Yee

Arcadia, California, 91007, United States

Location

Clintell, Inc.

Skokie, Illinois, 60077, United States

Location

CER - Instituto Medico

Buenos Aires, B1878dvb Bs. As., Argentina

Location

COIBA Centro de Oncologia e Investigacion

Berazategui, Buenos Aires, 01884, Argentina

Location

Damic-Fundacion Rusculleda

Córdoba, Argentina

Location

Centro Medico San Roque

San Miguel de Tucumán, T4000IAK, Argentina

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

St. George Hospital, Cancer Care Centre

Kogarah, New South Wales, 2217, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Calvary Mater Newcastle Hospital

Waratah, New South Wales, 2298, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Nambour General Hospital

Nambour, Queensland, 4560, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Western Hospital

Footscray, Victoria, 3011, Australia

Location

Frankston Hospital - Peninsula Oncology Centre

Frankston, Victoria, 3199, Australia

Location

Geelong Hospital

Geelong, Victoria, 3220, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Sir Charles Gairdner Hospital

Perth, Western Australia, 6009, Australia

Location

Centro de Oncologia e Radioterapia (COR) Mae de Deus

Porto Alegre, Rio Grande do Sul, 90840-440, Brazil

Location

Fundacao Pio XII - Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

ESHO - Empresa de Servicos Hospitalares Ltda.

Brasilia, São Paulo, 01321-001, Brazil

Location

Centro de Pesquisa Clinica do Hospital

Porto Alegre, São Paulo, 17210-120, Brazil

Location

Oxion Hospital Dia Oncologia LTDA - Oxion

Belo Horizonte, 30150-270, Brazil

Location

Unknown Facility

Centro, 98700-000, Brazil

Location

Nucleo de Oncologia da Bahia

Salvador, 40170-110, Brazil

Location

GRAM - Grupo de Assistencia Medica

São Paulo, 01224-010, Brazil

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Abbotsford Centre

Abbotsford, British Columbia, V2S 0C2, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Atlantic Health Sciences Corporation

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2S 0A9, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Centro di Riferimento Oncologico - CRO

Aviano, PN, 33081, Italy

Location

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

Saronno, VA, 21047, Italy

Location

U.O. di Oncologia Medica Azienda Ospedaliera G Rummo

Benevento, 82100, Italy

Location

Ospedale Santa Croce

Fano, 61032, Italy

Location

U.O. di Oncologia Ospedale Villa Scassi

Genova, 16149, Italy

Location

Intstituto Scientifico Romangnolo

Meldola, 47014, Italy

Location

U.O.C. Terapie Integrate in Oncologia,

Messina, 98125, Italy

Location

U.O.C. Oncologia Medica,

Messina, 98158, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

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

Mirano, 30035, Italy

Location

Dott. Fortunato Ciardiello,Cattedra Oncologia Medica

Napoli, 80131, Italy

Location

Unita Sperimentazioni Cliniche Istituto per lo

Napoli, 80131, Italy

Location

UOC Oncologia Medica II Instituto Oncologio Veneto

Padua, 35128, Italy

Location

La Maddalena, Dipartimento Oncologico

Palermo, Italy

Location

Azienda USL di Piacenza, Ospedale Gugliemimo Salieto

Piacenza, 29100, Italy

Location

Azienda Ospedaliera S. Camillo-Forlanin

Rome, 00152, Italy

Location

Policlinico Umberto I, Universita Sapienza

Rome, 00161, Italy

Location

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, 71013, Italy

Location

Ospedale E. Morelli-Sondalo

Sondalo, 23039, Italy

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Hospital Central De La Fuerza Aerea Del Peru

Lima, 18, Peru

Location

Hospital Nacional Luis N. Saenz

Lima, Peru

Location

Instituto de Oncologia y Radioterapia de

Lima, Peru

Location

Perpetual Succour Hospital

Cebu City, 6000, Philippines

Location

Makati Medical Center

Makati City, 1229, Philippines

Location

Phillippine General Hospital

Manila, 1000, Philippines

Location

Ajou University Hospital

Gyeonggi-do, 443-721, South Korea

Location

Chonnan National University Hwasun Hospital

Jeongnam, 519-763, South Korea

Location

Yonsei University College of Medicine

Seoul, 120-752, South Korea

Location

Seoul Veterans Hospital

Seoul, 134-791, South Korea

Location

The Catholic University of Korea,

Seoul, 137-701, South Korea

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

Chi-Mei Foundation Hospital

Tainan, 736, Taiwan

Location

Tri-Service General Hospital

Taipei, 114, Taiwan

Location

Chulalongkorn University

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Siriraj Hospital, Oncology Unit

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiangmai Hospital

Chiang Mai, 50200, Thailand

Location

Related Publications (2)

• Ellis PM, Shepherd FA, Millward M, Perrone F, Seymour L, Liu G, Sun S, Cho BC, Morabito A, Leighl NB, Stockler MR, Lee CW, Wierzbicki R, Cohen V, Blais N, Sangha RS, Favaretto AG, Kang JH, Tsao MS, Wilson CF, Goldberg Z, Ding K, Goss GD, Bradbury PA; NCIC CTG; Australasian Lung Cancer Trials Group; NCI Naples Clinical Trials Unit. Dacomitinib compared with placebo in pretreated patients with advanced or metastatic non-small-cell lung cancer (NCIC CTG BR.26): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1379-88. doi: 10.1016/S1470-2045(14)70472-3. Epub 2014 Oct 15.

  PMID: 25439692 RESULT

• Martin P, Shiau CJ, Pasic M, Tsao M, Kamel-Reid S, Lin S, Tudor R, Cheng S, Higgins B, Burkes R, Ng M, Arif S, Ellis PM, Hubay S, Kuruvilla S, Laurie SA, Li J, Hwang D, Lau A, Shepherd FA, Le LW, Leighl NB. Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients. Br J Cancer. 2016 Mar 15;114(6):616-22. doi: 10.1038/bjc.2016.22. Epub 2016 Feb 18.

  PMID: 26889973 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

dacomitinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Limitations and Caveats

Despite the eligibility requirement for tumor samples, samples were not available or inadequate for translational studies in 30 - 40% of patients. This does limits the power of the secondary analyses examining biomarker driven outcomes.

Results Point of Contact

• Title: Dr. Keyue Ding
• Organization: NCIC Clinical Trails Group

kding@ctg.queensu.ca

1-613-533-6000

Study Officials

• Peter Ellis, MD

  Margaret and Charles Juravinski Cancer Centre

  STUDY CHAIR

• Penny Bradbury, MD

  NCIC Clinical Trials Group

  STUDY CHAIR

• Michael Millward, MD

  Sir Charles Gairdner Hospital - Nedlands

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2009
• First Posted: October 22, 2009
• Study Start: December 23, 2009
• Primary Completion: January 15, 2014
• Study Completion: November 27, 2015
• Last Updated: August 22, 2023
• Results First Posted: October 27, 2014

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (21); AU (16); IT (19); PH (3); NZ (1); TW (3); US (2); KR (5); PE (3); AR (4); BR (8); TH (4)