PF-00299804 in Stage IIIB or Stage IV Non-Small Cell Lung Cancer Not Responding to Standard Therapy for Advanced or Metastatic Cancer
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: PF-00299804 Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. |
Drug: PF-00299804
PF-804 45 mg PO, daily
|
Placebo Comparator: Placebo Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. |
Drug: Placebo
Placebo 45 mg PO, daily
|
Outcome Measures
Primary Outcome Measures
- Overall Survival [42 Months]
Median and 95% confidence intervals
Secondary Outcome Measures
- Overall Survival in KRAS-WT Patients [42 Months]
Median and 95% confidence intervals of Overall survival in KRAS-WT patients
- Overall Survival in EGFR-mutant Patients [42 Months]
Overall survival by EGFR-mutantion subgroups
- Progression-free Survival [42 Months]
progression were evaluated using the revised international criteria (1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumours) committee
- Objective Response Rate [42 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 4.0 [42 Months]
Number of participants with Toxicities by treatment received according to NCI CTCAE version 4.0
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Shapiro, Stafford and Yee | Arcadia | California | United States | 91007 |
2 | Clintell, Inc. | Skokie | Illinois | United States | 60077 |
3 | CER - Instituto Medico | Buenos Aires | B1878dvb Bs. As. | Argentina | |
4 | COIBA Centro de Oncologia e Investigacion | Berazategui | Provincia De Buenos Aires | Argentina | 01884 |
5 | Damic-Fundacion Rusculleda | Cordoba | Argentina | ||
6 | Centro Medico San Roque | San Miguel de Tucuman | Argentina | T4000IAK | |
7 | Royal Prince Alfred Hospital | Camperdown | New South Wales | Australia | 2050 |
8 | Concord Repatriation General Hospital | Concord | New South Wales | Australia | 2139 |
9 | St. George Hospital, Cancer Care Centre | Kogarah | New South Wales | Australia | 2217 |
10 | Prince of Wales Hospital | Randwick | New South Wales | Australia | 2031 |
11 | Royal North Shore Hospital | St. Leonards | New South Wales | Australia | 2065 |
12 | Calvary Mater Newcastle Hospital | Waratah | New South Wales | Australia | 2298 |
13 | Westmead Hospital | Westmead | New South Wales | Australia | 2145 |
14 | The Prince Charles Hospital | Chermside | Queensland | Australia | 4032 |
15 | Nambour General Hospital | Nambour | Queensland | Australia | 4560 |
16 | Royal Adelaide Hospital | Adelaide | South Australia | Australia | 5000 |
17 | Monash Medical Centre | Clayton | Victoria | Australia | 3168 |
18 | Western Hospital | Footscray | Victoria | Australia | 3011 |
19 | Frankston Hospital - Peninsula Oncology Centre | Frankston | Victoria | Australia | 3199 |
20 | Geelong Hospital | Geelong | Victoria | Australia | 3220 |
21 | Austin Hospital | Heidelberg | Victoria | Australia | 3084 |
22 | Sir Charles Gairdner Hospital | Perth | Western Australia | Australia | 6009 |
23 | Centro de Oncologia e Radioterapia (COR) Mae de Deus | Porto Alegre | Rio Grande Do Sul | Brazil | 90840-440 |
24 | ESHO - Empresa de Servicos Hospitalares Ltda. | Brasilia | Sao Paulo | Brazil | 01321-001 |
25 | Fundacao Pio XII - Hospital de Cancer de Barretos | Barretos | SP | Brazil | 14784-400 |
26 | Centro de Pesquisa Clinica do Hospital | Porto Alegre | SP | Brazil | 17210-120 |
27 | Oxion Hospital Dia Oncologia LTDA - Oxion | Belo Horizonte | Brazil | 30150-270 | |
28 | Centro | Brazil | 98700-000 | ||
29 | Nucleo de Oncologia da Bahia | Salvador | Brazil | 40170-110 | |
30 | GRAM - Grupo de Assistencia Medica | Sao Paulo | Brazil | 01224-010 | |
31 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G 1Z2 |
32 | BCCA - Abbotsford Centre | Abbotsford | British Columbia | Canada | V2S 0C2 |
33 | BCCA - Fraser Valley Cancer Centre | Surrey | British Columbia | Canada | V3V 1Z2 |
34 | BCCA - Vancouver Cancer Centre | Vancouver | British Columbia | Canada | V5Z 4E6 |
35 | Atlantic Health Sciences Corporation | Saint John | New Brunswick | Canada | E2L 4L2 |
36 | Dr. H. Bliss Murphy Cancer Centre | St. John's | Newfoundland and Labrador | Canada | A1B 3V6 |
37 | QEII Health Sciences Centre | Halifax | Nova Scotia | Canada | B3H 1V7 |
38 | Juravinski Cancer Centre at Hamilton Health Sciences | Hamilton | Ontario | Canada | L8V 5C2 |
39 | Cancer Centre of Southeastern Ontario at Kingston | Kingston | Ontario | Canada | K7L 5P9 |
40 | London Regional Cancer Program | London | Ontario | Canada | N6A 4L6 |
41 | Lakeridge Health Oshawa | Oshawa | Ontario | Canada | L1G 2B9 |
42 | Ottawa Health Research Institute - General Division | Ottawa | Ontario | Canada | K1H 8L6 |
43 | Algoma District Cancer Program | Sault Ste. Marie | Ontario | Canada | P6B 0A8 |
44 | Niagara Health System | St. Catharines | Ontario | Canada | L2S 0A9 |
45 | Health Sciences North | Sudbury | Ontario | Canada | P3E 5J1 |
46 | Univ. Health Network-Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
47 | Windsor Regional Cancer Centre | Windsor | Ontario | Canada | N8W 2X3 |
48 | CHUM - Hopital Notre-Dame | Montreal | Quebec | Canada | H2L 4M1 |
49 | McGill University - Dept. Oncology | Montreal | Quebec | Canada | H2W 1S6 |
50 | Allan Blair Cancer Centre | Regina | Saskatchewan | Canada | S4T 7T1 |
51 | Saskatoon Cancer Centre | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
52 | Centro di Riferimento Oncologico - CRO | Aviano | PN | Italy | 33081 |
53 | A.O. Busto Arsizio - P.O. Saronno | Saronno | VA | Italy | 21047 |
54 | U.O. di Oncologia Medica Azienda Ospedaliera G Rummo | Benevento | Italy | 82100 | |
55 | Ospedale Santa Croce | Fano | Italy | 61032 | |
56 | U.O. di Oncologia Ospedale Villa Scassi | Genova | Italy | 16149 | |
57 | Intstituto Scientifico Romangnolo | Meldola | Italy | 47014 | |
58 | U.O.C. Terapie Integrate in Oncologia, | Messina | Italy | 98125 | |
59 | U.O.C. Oncologia Medica, | Messina | Italy | 98158 | |
60 | Ospedale San Raffaele | Milan | Italy | 20132 | |
61 | U.O.C. di Oncologia U.L.S.S. 13 | Mirano | Italy | 30035 | |
62 | Dott. Fortunato Ciardiello,Cattedra Oncologia Medica | Napoli | Italy | 80131 | |
63 | Unita Sperimentazioni Cliniche Istituto per lo | Napoli | Italy | 80131 | |
64 | UOC Oncologia Medica II Instituto Oncologio Veneto | Padova | Italy | 35128 | |
65 | La Maddalena, Dipartimento Oncologico | Palermo | Italy | ||
66 | Azienda USL di Piacenza, Ospedale Gugliemimo Salieto | Piacenza | Italy | 29100 | |
67 | Azienda Ospedaliera S. Camillo-Forlanin | Rome | Italy | 00152 | |
68 | Policlinico Umberto I, Universita Sapienza | Rome | Italy | 00161 | |
69 | Ospedale Casa Sollievo della Sofferenza | San Giovanni Rotondo | Italy | 71013 | |
70 | Ospedale E. Morelli-Sondalo | Sondalo | Italy | 23039 | |
71 | Ajou University Hospital | GyeongGi-Do | Korea, Republic of | 443-721 | |
72 | Chonnan National University Hwasun Hospital | Jeongnam | Korea, Republic of | 519-763 | |
73 | Yonsei University College of Medicine | Seoul | Korea, Republic of | 120-752 | |
74 | Seoul Veterans Hospital | Seoul | Korea, Republic of | 134-791 | |
75 | The Catholic University of Korea, | Seoul | Korea, Republic of | 137-701 | |
76 | Auckland City Hospital | Auckland | New Zealand | 1023 | |
77 | Hospital Central De La Fuerza Aerea Del Peru | Lima | Peru | 18 | |
78 | Hospital Nacional Luis N. Saenz | Lima | Peru | ||
79 | Instituto de Oncologia y Radioterapia de | Lima | Peru | ||
80 | Perpetual Succour Hospital | Cebu City | Philippines | 6000 | |
81 | Makati Medical Center | Makati City | Philippines | 1229 | |
82 | Phillippine General Hospital | Manila | Philippines | 1000 | |
83 | China Medical University Hospital | Taichung | Taiwan | 404 | |
84 | Chi-Mei Foundation Hospital | Tainan | Taiwan | 736 | |
85 | Tri-Service General Hospital | Taipei | Taiwan | 114 | |
86 | Chulalongkorn University | Bangkok | Thailand | 10330 | |
87 | Ramathibodi Hospital | Bangkok | Thailand | 10400 | |
88 | Siriraj Hospital, Oncology Unit | Bangkok | Thailand | 10700 | |
89 | Maharaj Nakorn Chiangmai Hospital | Chiangmai | Thailand | 50200 |
Sponsors and Collaborators
- NCIC Clinical Trials Group
- Pfizer
Investigators
- Study Chair: 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 Documents (Full-Text)
None provided.More Information
Publications
None provided.- BR26
- CAN-NCIC-BR26
- PFIZER-CAN-NCIC-BR26
- CDR0000657246
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | PF-804 | Placebo |
---|---|---|
Arm/Group Description | Study treatment arm | Control arm |
Period Title: Overall Study | ||
STARTED | 480 | 240 |
COMPLETED | 12 | 2 |
NOT COMPLETED | 468 | 238 |
Baseline Characteristics
Arm/Group Title | PF-00299804 | Placebo | Total |
---|---|---|---|
Arm/Group Description | Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PF-00299804: PF-804 45 mg PO, daily | Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Placebo: Placebo 45 mg PO, daily | Total of all reporting groups |
Overall Participants | 480 | 240 | 720 |
Age (years) [Median (Full Range) ] | |||
Median (Full Range) [years] |
63.5
|
65.5
|
64
|
Sex: Female, Male (Count of Participants) | |||
Female |
236
49.2%
|
120
50%
|
356
49.4%
|
Male |
244
50.8%
|
120
50%
|
364
50.6%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
2
0.4%
|
0
0%
|
2
0.3%
|
Asian |
172
35.8%
|
87
36.3%
|
259
36%
|
Native Hawaiian or Other Pacific Islander |
1
0.2%
|
0
0%
|
1
0.1%
|
Black or African American |
4
0.8%
|
1
0.4%
|
5
0.7%
|
White |
288
60%
|
144
60%
|
432
60%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
13
2.7%
|
8
3.3%
|
21
2.9%
|
Region of Enrollment (participants) [Number] | |||
United States |
1
0.2%
|
1
0.4%
|
2
0.3%
|
Philippines |
20
4.2%
|
11
4.6%
|
31
4.3%
|
Taiwan |
11
2.3%
|
6
2.5%
|
17
2.4%
|
Canada |
207
43.1%
|
101
42.1%
|
308
42.8%
|
Thailand |
28
5.8%
|
14
5.8%
|
42
5.8%
|
Brazil |
25
5.2%
|
14
5.8%
|
39
5.4%
|
Peru |
0
0%
|
1
0.4%
|
1
0.1%
|
Australia |
50
10.4%
|
27
11.3%
|
77
10.7%
|
New Zealand |
7
1.5%
|
4
1.7%
|
11
1.5%
|
Italy |
77
16%
|
34
14.2%
|
111
15.4%
|
Korea, Republic of |
47
9.8%
|
24
10%
|
71
9.9%
|
Argentina |
7
1.5%
|
3
1.3%
|
10
1.4%
|
Outcome Measures
Title | Overall Survival |
---|---|
Description | Median and 95% confidence intervals |
Time Frame | 42 Months |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | PF-00299804 | Placebo |
---|---|---|
Arm/Group Description | Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PF-00299804: PF-804 45 mg PO, daily | Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Placebo: Placebo 45 mg PO, daily |
Measure Participants | 480 | 240 |
Median (95% Confidence Interval) [Months] |
6.83
|
6.31
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | PF-00299804, Placebo |
---|---|---|
Comments | The trial was designed to detect a 25% deduction in risk of death with PF-804 with 90% power using a 1-sided 2.5% level significance test. The sample size was estimated as 720 patients. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.506 |
Comments | Stratified by stratification factors at randomization except study center, but included K-Ras mutation status.1-sied p-value. | |
Method | Log Rank | |
Comments | Stratified by stratification factors at randomization except study center, but included K-Ras mutation status. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.00 | |
Confidence Interval |
(2-Sided) 95% 0.83 to 1.21 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Overall Survival in KRAS-WT Patients |
---|---|
Description | Median and 95% confidence intervals of Overall survival in KRAS-WT patients |
Time Frame | 42 Months |
Outcome Measure Data
Analysis Population Description |
---|
Patients with K-Ras mutation wild type |
Arm/Group Title | PF-00299804 | Placebo |
---|---|---|
Arm/Group Description | Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PF-00299804: PF-804 45 mg PO, daily | Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Placebo: Placebo 45 mg PO, daily |
Measure Participants | 220 | 120 |
Median (95% Confidence Interval) [Months] |
7.00
|
5.19
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | PF-00299804, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.043 |
Comments | 1-sided p-value | |
Method | Log Rank | |
Comments | Stratified by stratification factors at randomization except study center. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.79 | |
Confidence Interval |
(2-Sided) 95% 0.61 to 1.03 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Overall Survival in EGFR-mutant Patients |
---|---|
Description | Overall survival by EGFR-mutantion subgroups |
Time Frame | 42 Months |
Outcome Measure Data
Analysis Population Description |
---|
Patients with EGFR mutation |
Arm/Group Title | PF-00299804 | Placebo |
---|---|---|
Arm/Group Description | Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PF-00299804: PF-804 45 mg PO, daily | Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Placebo: Placebo 45 mg PO, daily |
Measure Participants | 114 | 68 |
Median (95% Confidence Interval) [Months] |
7.23
|
7.52
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | PF-00299804, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.46 |
Comments | 1-sided pvalue | |
Method | Log Rank | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.98 | |
Confidence Interval |
(2-Sided) 95% 0.67 to 1.44 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Progression-free Survival |
---|---|
Description | progression were evaluated using the revised international criteria (1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumours) committee |
Time Frame | 42 Months |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | PF-00299804 | Placebo |
---|---|---|
Arm/Group Description | Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PF-00299804: PF-804 45 mg PO, daily | Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Placebo: Placebo 45 mg PO, daily |
Measure Participants | 480 | 240 |
Median (95% Confidence Interval) [Months] |
2.66
|
1.58
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | PF-00299804, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | < 0.0001 |
Comments | ||
Method | Log Rank | |
Comments | Stratified by stratification factors at randomization except study center, but included K-Ras mutation status. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.66 | |
Confidence Interval |
(2-Sided) 95% 0.55 to 0.79 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Objective Response Rate |
---|---|
Description | 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. |
Time Frame | 42 months |
Outcome Measure Data
Analysis Population Description |
---|
ITT |
Arm/Group Title | PF-00299804 | Placebo |
---|---|---|
Arm/Group Description | Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PF-00299804: PF-804 45 mg PO, daily | Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Placebo: Placebo 45 mg PO, daily |
Measure Participants | 480 | 240 |
Mean (95% Confidence Interval) [percentage of participants] |
7.1
1.5%
|
1.3
0.5%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | PF-00299804, Placebo |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.001 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 6.11 | |
Confidence Interval |
(2-Sided) 95% 1.84 to 20.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Number of Participants With Toxicity as Measured by NCI CTCAE Version 4.0 |
---|---|
Description | Number of participants with Toxicities by treatment received according to NCI CTCAE version 4.0 |
Time Frame | 42 Months |
Outcome Measure Data
Analysis Population Description |
---|
As treated population |
Arm/Group Title | PF-00299804 | Placebo |
---|---|---|
Arm/Group Description | Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PF-00299804: PF-804 45 mg PO, daily | Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Placebo: Placebo 45 mg PO, daily |
Measure Participants | 477 | 239 |
Number [participants] |
467
97.3%
|
223
92.9%
|
Adverse Events
Time Frame | 42 Months | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | PF-00299804 | Placebo | ||
Arm/Group Description | Patients receive oral PF-00299804 once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. PF-00299804: PF-804 45 mg PO, daily | Patients receive oral placebo once daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Placebo: Placebo 45 mg PO, daily | ||
All Cause Mortality |
||||
PF-00299804 | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
PF-00299804 | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 191/477 (40%) | 87/239 (36.4%) | ||
Blood and lymphatic system disorders | ||||
Anemia | 1/477 (0.2%) | 0/239 (0%) | ||
Febrile neutropenia | 1/477 (0.2%) | 1/239 (0.4%) | ||
Cardiac disorders | ||||
Atrial fibrillation | 0/477 (0%) | 1/239 (0.4%) | ||
Cardiac arrest | 1/477 (0.2%) | 0/239 (0%) | ||
Myocardial infarction | 1/477 (0.2%) | 1/239 (0.4%) | ||
Pericardial effusion | 1/477 (0.2%) | 2/239 (0.8%) | ||
Pericardial tamponade | 0/477 (0%) | 1/239 (0.4%) | ||
Pericarditis | 1/477 (0.2%) | 0/239 (0%) | ||
Ear and labyrinth disorders | ||||
Hearing impaired | 1/477 (0.2%) | 0/239 (0%) | ||
Endocrine disorders | ||||
Adrenal insufficiency | 0/477 (0%) | 1/239 (0.4%) | ||
Eye disorders | ||||
Cataract | 1/477 (0.2%) | 0/239 (0%) | ||
Corneal ulcer | 1/477 (0.2%) | 0/239 (0%) | ||
Gastrointestinal disorders | ||||
Abdominal distension | 1/477 (0.2%) | 0/239 (0%) | ||
Abdominal pain | 4/477 (0.8%) | 3/239 (1.3%) | ||
Anal hemorrhage | 1/477 (0.2%) | 0/239 (0%) | ||
Ascites | 1/477 (0.2%) | 0/239 (0%) | ||
Colitis | 1/477 (0.2%) | 0/239 (0%) | ||
Colonic obstruction | 1/477 (0.2%) | 0/239 (0%) | ||
Constipation | 3/477 (0.6%) | 0/239 (0%) | ||
Diarrhea | 17/477 (3.6%) | 1/239 (0.4%) | ||
Dysphagia | 0/477 (0%) | 2/239 (0.8%) | ||
Esophageal stenosis | 0/477 (0%) | 1/239 (0.4%) | ||
Gastrointestinal pain | 1/477 (0.2%) | 0/239 (0%) | ||
Ileus | 0/477 (0%) | 1/239 (0.4%) | ||
Mucositis oral | 5/477 (1%) | 0/239 (0%) | ||
Nausea | 5/477 (1%) | 0/239 (0%) | ||
Obstruction gastric | 0/477 (0%) | 1/239 (0.4%) | ||
Pancreatitis | 1/477 (0.2%) | 0/239 (0%) | ||
Small intestinal obstruction | 1/477 (0.2%) | 0/239 (0%) | ||
Upper gastrointestinal hemorrhage | 0/477 (0%) | 1/239 (0.4%) | ||
Vomiting | 8/477 (1.7%) | 3/239 (1.3%) | ||
General disorders | ||||
Chills | 1/477 (0.2%) | 0/239 (0%) | ||
Death NOS | 2/477 (0.4%) | 0/239 (0%) | ||
Fatigue | 4/477 (0.8%) | 2/239 (0.8%) | ||
Fever | 7/477 (1.5%) | 1/239 (0.4%) | ||
Gait disturbance | 1/477 (0.2%) | 0/239 (0%) | ||
Infusion site extravasation | 1/477 (0.2%) | 0/239 (0%) | ||
Non-cardiac chest pain | 1/477 (0.2%) | 0/239 (0%) | ||
Pain | 2/477 (0.4%) | 1/239 (0.4%) | ||
Sudden death NOS | 1/477 (0.2%) | 2/239 (0.8%) | ||
Hepatobiliary disorders | ||||
Hepatic failure | 1/477 (0.2%) | 0/239 (0%) | ||
Infections and infestations | ||||
Bronchial infection | 1/477 (0.2%) | 1/239 (0.4%) | ||
Enterocolitis infectious | 1/477 (0.2%) | 0/239 (0%) | ||
Lung infection | 32/477 (6.7%) | 12/239 (5%) | ||
Lymph gland infection | 1/477 (0.2%) | 0/239 (0%) | ||
Mucosal infection | 1/477 (0.2%) | 0/239 (0%) | ||
Other infections and infestations | 1/477 (0.2%) | 0/239 (0%) | ||
Scrotal infection | 1/477 (0.2%) | 0/239 (0%) | ||
Sepsis | 2/477 (0.4%) | 3/239 (1.3%) | ||
Skin infection | 1/477 (0.2%) | 0/239 (0%) | ||
Urinary tract infection | 2/477 (0.4%) | 0/239 (0%) | ||
Injury, poisoning and procedural complications | ||||
Fall | 1/477 (0.2%) | 0/239 (0%) | ||
Fracture | 3/477 (0.6%) | 1/239 (0.4%) | ||
Hip fracture | 3/477 (0.6%) | 0/239 (0%) | ||
Investigations | ||||
Neutrophil count decreased | 0/477 (0%) | 1/239 (0.4%) | ||
Weight loss | 0/477 (0%) | 1/239 (0.4%) | ||
Metabolism and nutrition disorders | ||||
Anorexia | 3/477 (0.6%) | 1/239 (0.4%) | ||
Dehydration | 16/477 (3.4%) | 0/239 (0%) | ||
Hypercalcemia | 0/477 (0%) | 1/239 (0.4%) | ||
Hyperglycemia | 0/477 (0%) | 1/239 (0.4%) | ||
Hypokalemia | 1/477 (0.2%) | 0/239 (0%) | ||
Hyponatremia | 1/477 (0.2%) | 0/239 (0%) | ||
Musculoskeletal and connective tissue disorders | ||||
Back pain | 2/477 (0.4%) | 2/239 (0.8%) | ||
Bone pain | 1/477 (0.2%) | 0/239 (0%) | ||
Chest wall pain | 1/477 (0.2%) | 1/239 (0.4%) | ||
Generalized muscle weakness | 2/477 (0.4%) | 0/239 (0%) | ||
Pain in extremity | 2/477 (0.4%) | 0/239 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Other neoplasms benign, malignant and unspecified | 79/477 (16.6%) | 43/239 (18%) | ||
Tumor pain | 2/477 (0.4%) | 0/239 (0%) | ||
Nervous system disorders | ||||
Cognitive disturbance | 0/477 (0%) | 1/239 (0.4%) | ||
Depressed level of consciousness | 4/477 (0.8%) | 0/239 (0%) | ||
Dizziness | 2/477 (0.4%) | 1/239 (0.4%) | ||
Dysphasia | 1/477 (0.2%) | 0/239 (0%) | ||
Encephalopathy | 1/477 (0.2%) | 0/239 (0%) | ||
Intracranial hemorrhage | 0/477 (0%) | 1/239 (0.4%) | ||
Ischemia cerebrovascular | 1/477 (0.2%) | 0/239 (0%) | ||
Other nervous system disorders | 1/477 (0.2%) | 0/239 (0%) | ||
Paresthesia | 0/477 (0%) | 1/239 (0.4%) | ||
Seizure | 1/477 (0.2%) | 0/239 (0%) | ||
Sinus pain | 1/477 (0.2%) | 0/239 (0%) | ||
Stroke | 2/477 (0.4%) | 3/239 (1.3%) | ||
Syncope | 0/477 (0%) | 1/239 (0.4%) | ||
Transient ischemic attacks | 0/477 (0%) | 1/239 (0.4%) | ||
Psychiatric disorders | ||||
Confusion | 3/477 (0.6%) | 1/239 (0.4%) | ||
Personality change | 0/477 (0%) | 1/239 (0.4%) | ||
Renal and urinary disorders | ||||
Acute kidney injury | 6/477 (1.3%) | 0/239 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Aspiration | 0/477 (0%) | 1/239 (0.4%) | ||
Bronchopulmonary hemorrhage | 6/477 (1.3%) | 4/239 (1.7%) | ||
Cough | 0/477 (0%) | 1/239 (0.4%) | ||
Dyspnea | 26/477 (5.5%) | 14/239 (5.9%) | ||
Epistaxis | 2/477 (0.4%) | 0/239 (0%) | ||
Hoarseness | 1/477 (0.2%) | 0/239 (0%) | ||
Hypoxia | 4/477 (0.8%) | 0/239 (0%) | ||
Pleural effusion | 7/477 (1.5%) | 3/239 (1.3%) | ||
Pleuritic pain | 1/477 (0.2%) | 0/239 (0%) | ||
Pneumonitis | 2/477 (0.4%) | 0/239 (0%) | ||
Pneumothorax | 2/477 (0.4%) | 1/239 (0.4%) | ||
Productive cough | 1/477 (0.2%) | 0/239 (0%) | ||
Pulmonary edema | 1/477 (0.2%) | 0/239 (0%) | ||
Respiratory failure | 6/477 (1.3%) | 2/239 (0.8%) | ||
Skin and subcutaneous tissue disorders | ||||
Other skin and subcutaneous tissue disorders | 2/477 (0.4%) | 1/239 (0.4%) | ||
Rash acneiform | 2/477 (0.4%) | 0/239 (0%) | ||
Stevens-Johnson syndrome | 1/477 (0.2%) | 0/239 (0%) | ||
Vascular disorders | ||||
Hypotension | 0/477 (0%) | 1/239 (0.4%) | ||
Other vascular disorders | 0/477 (0%) | 1/239 (0.4%) | ||
Thromboembolic event | 12/477 (2.5%) | 3/239 (1.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
PF-00299804 | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 465/477 (97.5%) | 219/239 (91.6%) | ||
Eye disorders | ||||
Conjunctivitis | 47/477 (9.9%) | 0/239 (0%) | ||
Dry eye | 41/477 (8.6%) | 5/239 (2.1%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 61/477 (12.8%) | 18/239 (7.5%) | ||
Constipation | 120/477 (25.2%) | 74/239 (31%) | ||
Diarrhea | 380/477 (79.7%) | 47/239 (19.7%) | ||
Dry mouth | 50/477 (10.5%) | 11/239 (4.6%) | ||
Dyspepsia | 39/477 (8.2%) | 12/239 (5%) | ||
Gastroesophageal reflux disease | 30/477 (6.3%) | 9/239 (3.8%) | ||
Mucositis oral | 206/477 (43.2%) | 8/239 (3.3%) | ||
Nausea | 168/477 (35.2%) | 59/239 (24.7%) | ||
Vomiting | 134/477 (28.1%) | 37/239 (15.5%) | ||
General disorders | ||||
Edema limbs | 57/477 (11.9%) | 28/239 (11.7%) | ||
Fatigue | 254/477 (53.2%) | 115/239 (48.1%) | ||
Fever | 42/477 (8.8%) | 15/239 (6.3%) | ||
Non-cardiac chest pain | 33/477 (6.9%) | 21/239 (8.8%) | ||
Pain | 93/477 (19.5%) | 50/239 (20.9%) | ||
Infections and infestations | ||||
Lung infection | 25/477 (5.2%) | 6/239 (2.5%) | ||
Paronychia | 142/477 (29.8%) | 0/239 (0%) | ||
Investigations | ||||
Weight loss | 73/477 (15.3%) | 23/239 (9.6%) | ||
Metabolism and nutrition disorders | ||||
Anorexia | 222/477 (46.5%) | 93/239 (38.9%) | ||
Musculoskeletal and connective tissue disorders | ||||
Back pain | 83/477 (17.4%) | 47/239 (19.7%) | ||
Bone pain | 48/477 (10.1%) | 20/239 (8.4%) | ||
Chest wall pain | 41/477 (8.6%) | 27/239 (11.3%) | ||
Pain in extremity | 79/477 (16.6%) | 35/239 (14.6%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Tumor pain | 31/477 (6.5%) | 13/239 (5.4%) | ||
Nervous system disorders | ||||
Dizziness | 55/477 (11.5%) | 25/239 (10.5%) | ||
Dysgeusia | 34/477 (7.1%) | 4/239 (1.7%) | ||
Headache | 53/477 (11.1%) | 29/239 (12.1%) | ||
Peripheral sensory neuropathy | 84/477 (17.6%) | 32/239 (13.4%) | ||
Psychiatric disorders | ||||
Anxiety | 30/477 (6.3%) | 20/239 (8.4%) | ||
Insomnia | 84/477 (17.6%) | 45/239 (18.8%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Bronchopulmonary hemorrhage | 25/477 (5.2%) | 14/239 (5.9%) | ||
Cough | 233/477 (48.8%) | 108/239 (45.2%) | ||
Dyspnea | 276/477 (57.9%) | 132/239 (55.2%) | ||
Epistaxis | 72/477 (15.1%) | 4/239 (1.7%) | ||
Productive cough | 58/477 (12.2%) | 32/239 (13.4%) | ||
Sore throat | 26/477 (5.5%) | 3/239 (1.3%) | ||
Skin and subcutaneous tissue disorders | ||||
Alopecia | 25/477 (5.2%) | 11/239 (4.6%) | ||
Dry skin | 171/477 (35.8%) | 27/239 (11.3%) | ||
Other skin and subcutaneous tissue disorders | 30/477 (6.3%) | 5/239 (2.1%) | ||
Palmar-plantar erythrodysesthesia syndrome | 55/477 (11.5%) | 2/239 (0.8%) | ||
Pruritus | 87/477 (18.2%) | 28/239 (11.7%) | ||
Rash acneiform | 283/477 (59.3%) | 24/239 (10%) | ||
Rash maculo-papular | 78/477 (16.4%) | 16/239 (6.7%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Keyue Ding |
---|---|
Organization | NCIC Clinical Trails Group |
Phone | 1-613-533-6000 ext 77705 |
kding@ctg.queensu.ca |
- BR26
- CAN-NCIC-BR26
- PFIZER-CAN-NCIC-BR26
- CDR0000657246