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 is currently recruiting participants.

Verified May 2013 by Pfizer

Sponsor:

Information provided by (Responsible Party):

Pfizer

ClinicalTrials.gov Identifier:

NCT01121575

First received: May 10, 2010

Last updated: May 3, 2013

Last verified: May 2013

History of Changes

Tracking Information

First Received Date ^ICMJE

May 10, 2010

Last Updated Date

May 3, 2013

Start Date ^ICMJE

August 2010

Estimated Primary Completion Date

August 2013 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]

Original Primary Outcome Measures ^ICMJE

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 ]

Change History

Complete list of historical versions of study NCT01121575 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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 ]

Original Secondary Outcome Measures ^ICMJE

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 ]

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

Brief Summary

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.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 1

Study Design ^ICMJE

Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Non Small Cell Lung Cancer

Intervention ^ICMJE

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.

Study Arm (s)

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

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

August 2013

Estimated Primary Completion Date

August 2013 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Pfizer CT.gov Call Center	1-800-718-1021
Contact: Pfizer Oncology Clinical Trial Information Service	1-877-369-9753	PfizerCancerTrials@emergingmed.com

Location Countries ^ICMJE

United States, Australia

Administrative Information

NCT Number ^ICMJE

NCT01121575

Other Study ID Numbers ^ICMJE

A8081006

Has Data Monitoring Committee

Responsible Party

Pfizer

Study Sponsor ^ICMJE

Pfizer

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Pfizer CT.gov Call Center

Pfizer

Information Provided By

Pfizer

Verification Date

May 2013

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

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