A Study Of PF-04449913 In Select Hematologic Malignancies Or With Dasatinib In Chronic Myeloid Leukemia (CML) - Full Text View

Sponsor:	Pfizer
Information provided by:	Pfizer
ClinicalTrials.gov Identifier:	NCT00953758

Purpose

This study examines the effect of a small molecule inhibitor to the Sonic Hedgehog pathway on select hematologic malignancies. Part two of the study will examine the effect of this inhibitor in combination with dasatinib.

Condition	Intervention	Phase
Hematologic Malignancies	Drug: PF-04449913 Drug: dasatinib	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety Study
Official Title:	A Phase 1 Study To Evaluate The Safety, Pharmacokinetics, And Pharmacodynamics Of PF-04449913, An Oral Hedgehog Inhibitor, Administered As Single Agent In Select Hematologic Malignancies Or In Combination With Dasatinib In Chronic Myeloid Leukemia (CML)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Dasatinib

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

To determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose of PF-04449913 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
To determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose of PF-04449913 when administered in combination with dasatinib [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Type, incidence, severity graded by NCI Common Terminology Criteria for Adverse Events [CTCAE], timing, seriousness, and relatedness of adverse events; vital signs and laboratory test abnormalities (Phase 1a). [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Pharmacodynamic biomarker modulation (Phase 1a). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Pharmacokinetic parameters of PF-04449913 (Phase 1a). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Overall response (OR), time to progression (TTP), duration of response and progression-free survival (PFS) as defined by disease specific clinical practice guidelines (Phase 1a). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
QTc interval (Phase 1a). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Variations in genes and/or gene products which influence Hedgehog signaling pathways in patient samples in response to treatment with PF-04449913 (Phase 1a). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Type, incidence, severity graded by the NCI Common Terminology Criteria for Adverse Events, timing, seriousness, and relatedness of adverse events; vital signs and laboratory test abnormalities of PF-04449913 in combination with dasatinib (Phase 1b) [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
Pharmacodynamic biomarker modulation (Phase 1b). [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Pharmacokinetic parameters of PF-04449913 and dasatinib (Phase 1b). [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Overall Response, TTP, duration of response and PFS, as defined by clinical practice guidelines for CML (Phase 1b). [ Time Frame: 9 months ] [ Designated as safety issue: No ]
QTc interval (Phase 1b). [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Variations in genes and/or gene products which influence Hedgehog signaling pathways in patient samples in response to treatment with PF-04449913 (Phase 1b). [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	94
Study Start Date:	January 2010
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: PF-04449913 Escalating doses of PF-04449913 administered as tablets PO QD (or BID depending on pharmacokinetics) on Day-11 and from Cycle1/Day1 onwards continuously in 28 day cycles Drug: dasatinib The doses to be evaluated are 100mg and 80 mg once daily in combination with PF-04449913. Dasatinib will be administered as a tablet, orally and continuously for 28 day cycles. Intra-patient dose escalations to 140 mg PO QD are permitted after cycle 1.

Arms

Assigned Interventions

1: Experimental

Drug: PF-04449913

Escalating doses of PF-04449913 administered as tablets PO QD (or BID depending on pharmacokinetics) on Day-11 and from Cycle1/Day1 onwards continuously in 28 day cycles

Drug: dasatinib

The doses to be evaluated are 100mg and 80 mg once daily in combination with PF-04449913. Dasatinib will be administered as a tablet, orally and continuously for 28 day cycles. Intra-patient dose escalations to 140 mg PO QD are permitted after cycle 1.

Eligibility

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

Criteria

Inclusion Criteria:

CML (any phase) is resistant or intolerant to two tyrosine kinase Inhibitors
CML T315I mutations
Bone marrow or peripheral blood must contain <40% blasts

Exclusion Criteria:

History of bone marrow, cord blood or peripheral blood stem cell transplant
Cardiac History
Known malabsorption syndrome

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00953758

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, California
Pfizer Investigational Site
La Jolla, California, United States, 92037
Pfizer Investigational Site
La Jolla, California, United States, 92093
Pfizer Investigational Site
San Diego, California, United States, 92103
United States, Washington
Pfizer Investigational Site
Seattle, Washington, United States, 98109-1023
Italy
Pfizer Investigational Site
Bologna, Italy, 40138

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, Inc. ( Director, Clinical Trial Disclosure Group )
Study ID Numbers:	B1371001
Study First Received:	August 4, 2009
Last Updated:	January 14, 2010
ClinicalTrials.gov Identifier:	NCT00953758 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Myelofibrosis Myelodysplastic Syndrome Acute myeloid Leukemia dasatinib Hedgehog inhibitor

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Hematologic Neoplasms
Hematologic Diseases
Myeloproliferative Disorders
Enzyme Inhibitors
Leukemia, Myeloid
Protein Kinase Inhibitors

Pharmacologic Actions
Leukemia
Neoplasms
Neoplasms by Site
Dasatinib
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bone Marrow Diseases

ClinicalTrials.gov processed this record on February 08, 2010