Last reviewed · How we verify

NCT00553254

Trial Of PF-00299804 In Patients With Advanced Refractory Lung Cancer

Completed Phase 2 Results posted Last updated 19 October 2020
What this trial tests

Phase 2 trial testing PF-00299804 in Carcinoma, Non Small Cell Lung in 55 participants. Completed in 17 July 2014.

Timeline
5 February 2008
Primary endpoint
3 August 2010
17 July 2014

Quick facts

Lead sponsorPfizer
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Maskingnone
Primary purposetreatment
Enrollment55
Start date5 February 2008
Primary completion3 August 2010
Estimated completion17 July 2014
Sites3 locations across South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non Small Cell Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Recommended Phase 2 Dose (RP2D) - Phase 1 Primary · Baseline up to Day 21

The highest dose at which less than (\<) 33 percent (%) of participants experienced dose-limiting toxicities (DLT) was to be designated as the maximum tolerated dose (MTD) as well as the RP2D. DLT was defined as any of the following events: Grade 3/4 (severe or life-threatening/ disabling adverse event \[AE\]) nausea, vomiting, or diarrhea (despite the use of adequate/maximal medical intervention and/or prophylaxis); Grade greater than or equal to (\>=) 3 (severe or life-threatening/disabling AE or death related to AE) non-hematological toxicity; delayed (which delayed scheduled treatment for

GroupValue95% CI
PF-00299804 - Phase 1 All Participants45
Progression-Free Survival (PFS) at Month 4 (PFS4m) - Phase 2 Primary · Month 4

PFS4m was defined as percent chance of being event free (event defined as progressive disease \[PD\] or death due to any cause, whichever occurred first) at 4 months. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LD) 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.

GroupValue95% CI
PF-00299804 45 mg - Phase 247.231.6 – 61.3
Progression-Free Survival (PFS) at Month 6 (PFS6m) - Phase 2 Secondary · Month 6

PFS6m was defined as percent chance of being event free (event defined as PD or death due to any cause, whichever occurred first) at 6 months. Progression was defined using RECIST, as at least 20% increase in the sum of longest dimensions (LD) 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.

GroupValue95% CI
PF-00299804 45 mg - Phase 224.812.9 – 38.7
Overall Survival (OS) at Month 6 (OS6m) - Phase 2 Secondary · Month 6

OS6m was defined as percent chance of being alive at Month 6.

GroupValue95% CI
PF-00299804 45 mg - Phase 280.765.1 – 89.9
Percentage of Participants With Objective Response - Phase 1 Secondary · Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after end of treatment (EOT) (EOT: up to Day 506)

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. CR: disappearance of all target and non-target lesions. PR: at least 30 % decrease in sum of the longest dimensions (LDs) of target lesion, taking as reference the baseline sum LD, associated to non-progressive disease response for non-target lesions. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.

GroupValue95% CI
PF-00299804 30 mg - Phase 10.00.0 – 45.9
PF-00299804 45 mg - Phase 133.34.3 – 77.7
Soluble Protein Biomarkers Level Secondary · Cycle 1 Day 1 (C1D1, Baseline), Day 1 of each odd-numbered cycle up to Cycle 17 for both Phase 1 and Phase 2

Blood specimens were analyzed at a sponsor-designated laboratory for analysis of shed proteins/receptors related to Human Epidermal Growth Factor Receptor (HER) signaling (epidermal growth factor receptor \[EGFR\], HER2). These measurements were determined by enzyme-linked immunosorbent assay (ELISA). The data for all Phase 1 participants was combined for this outcome.

EGFR: C1D1
GroupValue95% CI
PF-00299804 - Phase 1 All Participants58.57± 7.498
PF-00299804 45 mg - Phase 257.41± 13.146
EGFR: C3D1
GroupValue95% CI
PF-00299804 - Phase 1 All Participants47.46± 7.845
PF-00299804 45 mg - Phase 250.81± 11.465
EGFR: C5D1
GroupValue95% CI
PF-00299804 - Phase 1 All Participants46.76± 5.395
PF-00299804 45 mg - Phase 258.87± 13.627
EGFR: C7D1
GroupValue95% CI
PF-00299804 - Phase 1 All Participants48.58± NA
PF-00299804 45 mg - Phase 255.83± 19.34
EGFR: C9D1
GroupValue95% CI
PF-00299804 - Phase 1 All Participants42.83± NA
PF-00299804 45 mg - Phase 250.32± 26.214
EGFR: C11D1
GroupValue95% CI
PF-00299804 - Phase 1 All Participants40.98± NA
PF-00299804 45 mg - Phase 263.69± 28.908
EGFR: C13D1
GroupValue95% CI
PF-00299804 - Phase 1 All Participants67.34± NA
PF-00299804 45 mg - Phase 273.26± 29.487
EGFR: C15D1
GroupValue95% CI
PF-00299804 - Phase 1 All Participants52± NA
PF-00299804 45 mg - Phase 249.45± 14.358
Number of Participants With Epidermal Growth Factor Receptor (EGFR), Kirsten Rat Sarcoma (KRAS), and Human Epidermal Growth Factor Receptor-2 (HER2) Mutation Status Secondary · Screening

Tumor tissue was analyzed at a sponsor-designated laboratory to investigate EGFR, KRAS and HER2 status (wild type or mutated). Participants who did not provide samples for central laboratory analysis confirmation were classified as "unknown". The data for all Phase 1 participants was combined for this outcome.

EGFR Status: Wild Type
GroupValue95% CI
PF-00299804 - Phase 1 All Participants3
PF-00299804 45 mg - Phase 23
EGFR Status: Mutant
GroupValue95% CI
PF-00299804 - Phase 1 All Participants2
PF-00299804 45 mg - Phase 212
EGFR Status: Unknown
GroupValue95% CI
PF-00299804 - Phase 1 All Participants7
PF-00299804 45 mg - Phase 228
KRAS Status: Wild Type
GroupValue95% CI
PF-00299804 - Phase 1 All Participants9
PF-00299804 45 mg - Phase 229
KRAS Status: Mutant
GroupValue95% CI
PF-00299804 - Phase 1 All Participants0
PF-00299804 45 mg - Phase 20
KRAS Status: Unknown
GroupValue95% CI
PF-00299804 - Phase 1 All Participants3
PF-00299804 45 mg - Phase 214
HER2 Status: Wild Type
GroupValue95% CI
PF-00299804 - Phase 1 All Participants0
PF-00299804 45 mg - Phase 29
HER2 Status: Mutant
GroupValue95% CI
PF-00299804 - Phase 1 All Participants0
PF-00299804 45 mg - Phase 21
Maximum Observed Plasma Concentration (Cmax) of PF-00299804 30 mg and PF-00299804 45 mg Secondary · 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9 for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2

Data in "PF-00299804 45 mg" treatment arm at Cycle 0 Day -9 (C0D-9) represents participants from Phase 1 only and at C1D14 represents participants from both Phase 1 and Phase 2.

C0D-9
GroupValue95% CI
PF-00299804 30 mg - Phase 113.34± 4.8205
PF-00299804 45 mg21.30± 12.356
C1D14
GroupValue95% CI
PF-00299804 30 mg - Phase 156.96± 20.572
PF-00299804 45 mg82.71± 38.788
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-00299804 30 mg and PF-00299804 45 mg Secondary · 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on Cycle 0 Day -9 (C0D-9) for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2

Data in "PF-00299804 45 mg" treatment arm at C0D-9 represents participants from Phase 1 only and at C1D14 represents participants from both Phase 1 and Phase 2.

C0D-9
GroupValue95% CI
PF-00299804 30 mg - Phase 18.004.17 – 24.0
PF-00299804 45 mg4.961.98 – 8.00
C1D14
GroupValue95% CI
PF-00299804 30 mg - Phase 15.030.000 – 24.0
PF-00299804 45 mg6.100.000 – 24.0
Plasma Decay Half-Life (t1/2) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1 Secondary · 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on Cycle 0 Day -9 (C0D-9)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

GroupValue95% CI
PF-00299804 30 mg - Phase 163.60± 30.271
PF-00299804 45 mg - Phase 154.02± 13.461
Area Under the Curve From Time Zero to 24 Hour Post-Dose (AUC0-24) of PF-00299804 30 mg and PF-00299804 45 mg Secondary · 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on Cycle 0 Day -9 (C0D-9) for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2

AUC0-24: Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post dose. Data in "PF- 00299804 45 mg" treatment arm at C0D-9 represents participants from Phase 1 only and at C1D14 represents participants from both Phase 1 and Phase 2.

C0D-9
GroupValue95% CI
PF-00299804 30 mg - Phase 1221.6± 87.063
PF-00299804 45 mg354.8± 153.31
C1D14
GroupValue95% CI
PF-00299804 30 mg - Phase 11075± 515.66
PF-00299804 45 mg1621± 664.87
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-00299804 30 mg and PF-00299804 45 mg- Phase 1 Secondary · 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9

AUClast: Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration.

GroupValue95% CI
PF-00299804 30 mg - Phase 1893.4± 516.50
PF-00299804 45 mg - Phase 11248± 522.11

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were recorded from the time that the participant provided informed consent through and including 28 calendar days after the last administration of the investigational product.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PF-00299804 30 mg - Phase 1
Serious: 1/6 (17%)
Deaths:
PF-00299804 45 mg - Phase 1
Serious: 0/6 (0%)
Deaths:
PF-00299804 45 mg - Phase 2
Serious: 9/43 (21%)
Deaths:

Serious adverse events (7 terms)

ReactionSystemPF-00299804 30 mg - Phase 1PF-00299804 45 mg - Phase 1PF-00299804 45 mg - Phase 2
Disease progressionGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
PneumoniaInfections and infestations
HydrocephalusNervous system disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Other adverse events (56 terms — click to expand)

ReactionSystemPF-00299804 30 mg - Phase 1PF-00299804 45 mg - Phase 1PF-00299804 45 mg - Phase 2
DiarrhoeaGastrointestinal disorders
Dermatitis acneiformSkin and subcutaneous tissue disorders
ParonychiaInfections and infestations
StomatitisGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
NauseaGastrointestinal disorders
Mucosal inflammationGeneral disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DyspepsiaGastrointestinal disorders
Productive coughRespiratory, thoracic and mediastinal disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Rash erythematousSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
Flank painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Nasal inflammationRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
AstheniaGeneral disorders
Chest painGeneral disorders
PyrexiaGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Nasal disorderRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Chest discomfortGeneral disorders
FolliculitisInfections and infestations
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
Skin exfoliationSkin and subcutaneous tissue disorders
Hearing impairedEar and labyrinth disorders

Most-reported serious reactions: Disease progression, Febrile neutropenia, Diarrhoea, Pneumonia, Hydrocephalus, Pleural effusion, Hypotension.

Data from ClinicalTrials.gov NCT00553254 adverse events section.

Sponsor's own description

To assess the safety and efficacy of PF-00299804 in patients with advanced lung cancer.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Phase I dose-escalation study of the pan-HER inhibitor, PF299804, in patients with advanced malignant solid tumors.
    Jänne PA, Boss DS, Camidge DR, Britten CD, et al · · 2011 · cited 146× · PMID 21220471 · DOI 10.1158/1078-0432.ccr-10-1220

Verify or expand the search:

Other trials of PF-00299804

Trials testing the same drug.

Other recruiting trials for Carcinoma, Non Small Cell Lung

Currently open trials in the same condition.

Other Pfizer trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00553254.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing