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

Purpose

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.

Condition	Intervention	Phase
Non Small Cell Lung Cancer	Drug: COMBINED PF-02341066 AND PF-00299804 Drug: PF-00299804 FOLLOWED BY COMBINED PF-02341066 AND PF-00299804	Phase 1

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Crizotinib

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	70
Study Start Date:	August 2010
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1 Patients will be treated with combined cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804).	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
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).	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.

Arms

Assigned Interventions

Experimental: Arm 1

Patients will be treated with combined cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804).

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

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).

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01121575

Contacts

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

Locations

United States, Colorado
Pfizer Investigational Site	Recruiting
Aurora, Colorado, United States, 80045
United States, Maryland
Pfizer Investigational Site	Recruiting
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Pfizer Investigational Site	Recruiting
Boston, Massachusetts, United States, 02114
Pfizer Investigational Site	Recruiting
Boston, Massachusetts, United States, 02215
Pfizer Investigational Site	Recruiting
Boston, Massachusetts, United States, 02115
Australia, Victoria
Pfizer Investigational Site	Recruiting
East Melbourne, Victoria, Australia, 3002

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01121575 History of Changes
Other Study ID Numbers:	A8081006
Study First Received:	May 10, 2010
Last Updated:	May 3, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

Phase 1 acquired resistance to erlotinib or gefitinib cMET inhibitor EGFR inhibitor panHER inhibitor combination trial Crizotinib

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms

Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 21, 2013