A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01121575
First received: May 10, 2010
Last updated: March 6, 2014
Last verified: March 2014

May 10, 2010
March 6, 2014
August 2010
February 2014   (final data collection date for primary outcome measure)
Overall safety profile of combined PF 02341066 plus PF 00299804 including adverse events (AE), as defined and graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], and first cycle Dose Limiting Toxicity. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
Overall safety profile of combined PF 02341066 plus PF 00299804 including adverse events (AE), as defined and graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], Version 4.02, and first cycle DLTs. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01121575 on ClinicalTrials.gov Archive Site
  • Plasma concentrations and pharmacokinetic (PK) parameters of PF 02341066 and PF 00299804 including AUCtau, Cmax, Ctrough, Tmax, and CLss/F. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Clinical activity of combined PF 02341066 plus PF 00299804 including objective response (OR) and stable disease (SD) as defined by RECIST version 1.1, duration of response (DR) and progression free survival (PFS). [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Biomarkers in tumor and blood that are potentially predictive for drug activity: for example, KRAS mutations, EGFR mutations (eg, T790M), EGFR and HER2 amplifications, c Met amplification and mutations, ALK, PTEN and PIK3A status in tumor biopsies. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Pharmacodynamic biomarkers in tumor biopsies (e.g., phospho c Met, c Met, EGFR, phospho EGFR) and in blood (e.g., HGF and s Met) that are modulated following drug exposure. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Plasma concentrations and pharmacokinetic (PK) parameters of PF 02341066 and PF 00299804 including AUCtau, Cmax, Ctrough, Tmax, and CLss/F. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Clinical activity of combined PF 02341066 plus PF 00299804 including objective response (OR) and stable disease (SD) as defined by RECIST version 1.1, duration of response (DR) and progression free survival (PFS). [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Biomarkers in tumor and blood that are potentially predictive for drug activity: for example, KRAS mutations, EGFR mutations (eg, T790M), EGFR and HER2 amplifications, c Met amplification and mutations, ALK, PTEN and PIK3A status in tumor biopsies. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Pharmacodynamic biomarkers in tumor biopsies (for example, phospho c Met, c Met, caspase 3, Ki67, ERBB3 (HER3), phospho ERBB3, EGFR, phospho EGFR, AKT, phospho AKT, S6, and phospho S6) and in blood (for example, HGF and s Met) that are potentially [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • modulated following drug exposure. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer
A Phase 1, Open Label, Dose Escalation Study To Evaluate Safety, Pharmacokinetics And Pharmacodynamics Of Combined Oral C- MET/ALK Inhibitor (PF- 02341066) And PAN-HER Inhibitor (PF- 00299804) In Patients With Advanced Non-Small Cell Lung Cancer

Lung cancer tumors become resistant to the first generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib by changing and increasing the activity of two cell signaling pathways: the cMET pathway and the EGFR pathway. Both resistance mechanisms can occur at the same time, in the same patient and even in the same tumor. This study combines a second generation EGFR inhibitor and a cMET inhibitor to block both these pathways in order to overcome resistance and treat this disease.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Non Small Cell Lung Cancer
  • Drug: COMBINED PF-02341066 AND PF-00299804
    The starting doses will be 200 mg by mouth, twice a day of PF 02341066 in tablet form and 30 mg by mouth once a day of PF 0029804 in tablet form. The dose of each drug in the combination will be escalated or de-escalated until the maximum tolerated combined dose is reached. Patients will then be treated with the maximum tolerated combined dose.
    Other Name: cMET inhibitor AND panHER inhibitor
  • Drug: PF-00299804 FOLLOWED BY COMBINED PF-02341066 AND PF-00299804
    45 mg by mouth once a day of PF-00299804 in tablet form until progressive disease and then the maximum tolerated combined dose of PF-02341066 (given by mouth twice a day in tablet form) and PF-00299804 (given by mouth once a day in tablet form).
    Other Name: panHER inhibitor FOLLOWED BY COMBINED cMET inhibitor AND panHER inhibitor.
  • Experimental: Arm 1
    Patients will be treated with combined cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804).
    Intervention: Drug: COMBINED PF-02341066 AND PF-00299804
  • Experimental: Arm 2
    Patients will be treated with single agent panHER inhibitor (PF-00299804) until disease progression and then with the maximum tolerated combined dose of cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804).
    Intervention: Drug: PF-00299804 FOLLOWED BY COMBINED PF-02341066 AND PF-00299804
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
70
February 2014
February 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • advanced non small cell lung cancer (dose escalation phase)
  • acquired resistance to erlotinib or gefitinib (expansion phase)
  • mandatory entrance biopsy (expansion phase)

Exclusion Criteria:

  • interstitial lung disease
  • unstable brain metastases
  • leptomeningeal disease
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia
 
NCT01121575
A8081006
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP