A Study Of Oral PF-02341066, A c-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer - Full Text View

Sponsor:	Pfizer
Information provided by (Responsible Party):	Pfizer
ClinicalTrials.gov Identifier:	NCT00585195

Purpose

PF-02341066 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-02341066 is a new class of drugs called c-Met/Hepatocyte growth factor receptor tyrosine kinase inhibitors. This compound is also an inhibitor of the anaplastic lymphoma kinase (called ALK) tyrosine kinase and ROS receptor tyrosine kinases. This research study is the first time PF-02341066 will be given to people. PF-02341066 is taken by mouth daily.

Condition	Intervention	Phase
Systemic Anaplastic Large-Cell Lymphoma Neoplasms Anaplastic Lymphoma Kinase, Human NSCLC	Drug: PF-02341066 Drug: Rifampin Drug: Ketoconazole	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 1 Safety, Pharmacokinetic And Pharmacodynamic Study Of PF-02341066, A c-Met/HGFR Selective Tyrosine Kinase Inhibitor, Administered Orally To Patients With Advanced Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Tyrosine Rifampin Ketoconazole Crizotinib

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

To test the safety of PF-02341066 when taken by people who have cancer [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]
To assess how the body handles blood concentrations of PF-02341066 [ Time Frame: 2.0 years ] [ Designated as safety issue: No ]
To find the dose of PF-02341066 that should be used in future clinical trials [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Anti-tumor activity [ Time Frame: 4.0 years ] [ Designated as safety issue: No ]
To assess how the body handles blood concentrations of PF-02341066 in the presence of another drug, rifampin [ Time Frame: 2.0 years ] [ Designated as safety issue: No ]
To assess how the body handles blood concentrations of PF-02341066 in the presence of another drug, ketoconazole [ Time Frame: 3.0 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	475
Study Start Date:	April 2006
Estimated Study Completion Date:	July 2015
Estimated Primary Completion Date:	July 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: PF-02341066 Escalating doses of PF-02341066 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg to 2000 mg/day administered either once or twice a day. A treatment cycle is considered to be 28 days (or 21 days depending on the cohort). Drug: Rifampin 600 mg QD administered from Cycle 1, Day 16 to Cycle 2, Day 1 (14 days of dosing) in combination with PF-02341066. Drug: Ketoconazole 200 mg BID administered from Cycle 1, Day 16 to Cycle 2, Day 1 (Cycle 2, Day 1 morning dose only; 13.5 days of dosing) in combination with PF-02341066.

Arms

Assigned Interventions

Experimental: 1

Drug: PF-02341066

Escalating doses of PF-02341066 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg to 2000 mg/day administered either once or twice a day. A treatment cycle is considered to be 28 days (or 21 days depending on the cohort).

Drug: Rifampin

600 mg QD administered from Cycle 1, Day 16 to Cycle 2, Day 1 (14 days of dosing) in combination with PF-02341066.

Drug: Ketoconazole

200 mg BID administered from Cycle 1, Day 16 to Cycle 2, Day 1 (Cycle 2, Day 1 morning dose only; 13.5 days of dosing) in combination with PF-02341066.

Eligibility

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

Criteria

Inclusion Criteria:

Advanced malignancies (except leukemias), histologically proven at diagnosis; Histologically confirmed advanced malignancies that are known to be sensitive to PF-03241066 inhibition, e.g. ALK, c-MET and ROS
Solid tumors must have measurable disease (Recommended Phase 2 Dose Cohort patients with non-measurable disease may enter on a case-by-case basis); not required for DDI sub-studies.
Adequate blood cell counts, kidney function, liver function and Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (for the Recommended Phase 2 Cohort, a ECOG score of 2 may be allowed on a case-by-case basis)

Exclusion Criteria:

Major surgery, radiation therapy or anti-cancer therapy within 2 to 4 weeks of starting study treatment, depending on the patient cohort
Prior stem cell transplant except of patients with neuroblastoma, lymphoma or myeloma
Active or unstable cardiac disease or heart attack within 6 months of starting study treatment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00585195

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	Recruiting
Orange, California, United States, 92868
United States, Colorado
Pfizer Investigational Site	Recruiting
Aurora, Colorado, United States, 80045
United States, Illinois
Pfizer Investigational Site	Recruiting
Chicago, Illinois, United States, 60637
United States, Massachusetts
Pfizer Investigational Site	Recruiting
Boston, Massachusetts, United States, 02115
Pfizer Investigational Site	Recruiting
Boston, Massachusetts, United States, 02114
United States, Michigan
Pfizer Investigational Site	Recruiting
Dearborn, Michigan, United States, 48124
Pfizer Investigational Site	Recruiting
Detroit, Michigan, United States, 48201
Pfizer Investigational Site	Recruiting
Southfield, Michigan, United States, 48034
Pfizer Investigational Site	Recruiting
Warren, Michigan, United States, 48093
United States, New York
Pfizer Investigational Site	Active, not recruiting
New York, New York, United States, 10021
Pfizer Investigational Site	Active, not recruiting
New York, New York, United States, 10022
Australia, Victoria
Pfizer Investigational Site	Recruiting
East Melbourne, Victoria, Australia, 3002
Korea, Republic of
Pfizer Investigational Site	Recruiting
Seoul, Korea, Republic of, 110-744

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 by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ou SH, Azada M, Dy J, Stiber JA. Asymptomatic profound sinus bradycardia (heart rate ?45) in non-small cell lung cancer patients treated with crizotinib. J Thorac Oncol. 2011 Dec;6(12):2135-7.

Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct;12(11):1004-12. Epub 2011 Sep 18.

Kijima T, Takeuchi K, Tetsumoto S, Shimada K, Takahashi R, Hirata H, Nagatomo I, Hoshino S, Takeda Y, Kida H, Goya S, Tachibana I, Kawase I. Favorable response to crizotinib in three patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion-type oncogene-positive non-small cell lung cancer. Cancer Sci. 2011 Aug;102(8):1602-4.

Ou SH, Kwak EL, Siwak-Tapp C, Dy J, Bergethon K, Clark JW, Camidge DR, Solomon BJ, Maki RG, Bang YJ, Kim DW, Christensen J, Tan W, Wilner KD, Salgia R, Iafrate AJ. Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J Thorac Oncol. 2011 May;6(5):942-6.

Costa DB, Kobayashi S, Pandya SS, Yeo WL, Shen Z, Tan W, Wilner KD. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol. 2011 May 20;29(15):e443-5. Epub 2011 Mar 21. No abstract available.

Butrynski JE, D'Adamo DR, Hornick JL, Dal Cin P, Antonescu CR, Jhanwar SC, Ladanyi M, Capelletti M, Rodig SJ, Ramaiya N, Kwak EL, Clark JW, Wilner KD, Christensen JG, Jänne PA, Maki RG, Demetri GD, Shapiro GI. Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med. 2010 Oct 28;363(18):1727-33.

Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703.

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00585195 History of Changes
Other Study ID Numbers:	A8081001
Study First Received:	December 29, 2007
Last Updated:	May 8, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

Crizotinib
Tumors positive for ALK/c-Met/ rearrangements
mutations or amplifications
Tumors with chromosomal translocations at the ROS gene

Additional relevant MeSH terms:

Neoplasms
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, T-Cell
Ketoconazole

Rifampin
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 22, 2012