A Study of XL184 With or Without Erlotinib in Adults With Non-Small Cell Lung Cancer - Full Text View

Sponsored by:	Exelixis
Information provided by:	Exelixis
ClinicalTrials.gov Identifier:	NCT00596648

Purpose

In Phase 1 of this study, the purpose is to evaluate the safety, tolerability, and highest safe dose of the multiple receptor tyrosine kinase inhibitor (including VEGFR2, MET, and RET) XL184 in combination with the EGFR inhibitor erlotinib administered to adults with Non-Small-Cell Lung Cancer (NSCLC). In Phase 2 of this study, the purpose is to evaluate the objective response rate of daily oral administration of XL184 with or without erlotinib in subjects with NSCLC who have progressed after responding to treatment with erlotinib. Target enrollment of Phase 1 is approximately 18 subjects, and target enrollment in Phase 2 is up to 68 subjects (34 subjects in each arm).

Condition	Intervention	Phase
Carcinoma, Non-Small-Cell Lung	Drug: XL184 Drug: erlotinib	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase 1/2 Study of XL184 With or Without Erlotinib in Subjects With Non-Small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by Exelixis:

Primary Outcome Measures:

In Phase 1 of the study: evaluate safety, tolerability, and maximum tolerated dose of daily oral administration of XL184 in combination with erlotinib to subjects with NSCLC [ Time Frame: Assessed at each visit ] [ Designated as safety issue: Yes ]
In Phase 1 of the study, to evaluate pharmacodynamic effects of XL184 administration either alone or in combination with erlotinib [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]
In Phase 1 of the study, to characterize pharmacokinetic parameters of single agent erlotinib, and of XL184 in combination with erlotinib [ Time Frame: Assessed at periodic visits (approx. every 8 weeks) ] [ Designated as safety issue: No ]
In Phase 2 of the study, to estimate the objective response rate of XL184 with or without erlotinib in adults with NSCLC who have progressed after responding to erlotinib [ Time Frame: Assessed approx. every 8 weeks ] [ Designated as safety issue: No ]
In Phase 2 of the study, to assess pharmacodynamic effects of XL184 administration either alone or with erlotinib [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]
In Phase 2 of the study, to characterize pharmacokinetic parameters of XL184 as a single agent and XL184 in combination with erlotinib in subjects with NSCLC [ Time Frame: Assessed at periodic visits (approx. every 8 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

In Phase 1 of the study, to assess response rate, progression-free survival, duration of response, and overall survival in subjects with NSCLC following treatment with XL184 either alone or in combination with erlotinib [ Time Frame: Assessed approx. every 8 weeks ] [ Designated as safety issue: No ]
In Phase 2 of the study, to evaluate the long-term safety and tolerability of XL184 administered either alone or in combination with erlotinib [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: Yes ]
In Phase 2 of the study, to assess progression-free survival, duration of response, and overall survival following treatment with XL184 either alone or in combination with erlotinib [ Time Frame: Assessed at periodic visits (approx. every 8 weeks) ] [ Designated as safety issue: No ]

Estimated Enrollment:	86
Study Start Date:	December 2007
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Phase 1 Arm: Experimental Escalating doses of XL184 + erlotinib	Drug: XL184 Capsules administered orally daily Drug: erlotinib Capsules administered orally daily.
Phase 2 Arm 1: Experimental XL184 + erlotinib (dose determined from Phase 1 portion of study)	Drug: XL184 Capsules administered orally daily Drug: erlotinib Capsules administered orally daily.
Phase 2 Arm 2: Experimental XL184 administered as a single agent 175 mg	Drug: XL184 Capsules administered orally daily

Eligibility

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

Criteria

Inclusion Criteria:

Histologically confirmed NSCLC and Stage 3b or 4 NSCLC (Phase 1 only) or Stage 3a with pleural effusion, Stage 3b or 4 NSCLC (Phase 2 only)
Documented progressive disease following a prior RECIST response to monotherapy with erlotinib OR documented progressive disease following stable disease of at least 6 months on monotherapy with erlotinib (Phase 2 only)
Measurable disease per RECIST (Phase 2 only)
At least 18 years old
Life expectancy greater than 3 months
ECOG performance status of 0 or 1
Adequate organ and marrow function
Capable of understanding and complying with the protocol, and written informed consent
Female subjects of childbearing potential must have a negative pregnancy test at enrollment

Exclusion Criteria:

Received anti-cancer treatment within 4 weeks, except erlotinib, prior to first dose (Phase 1 only)
In Phase 2 only: the subject has received:
- Radiation to ≥25% of his or her bone marrow within 4 weeks of the first dose of study drug OR
- Small molecule inhibitors of VEGFR2/KDR OR
- An investigational anti-cancer agent within 4 weeks of the first dose of study drug OR
- An investigational agent that targets EGF or EGFR at any time OR
- An approved agent that targets EGF or EGFR (with the exception of erlotinib and gefitinib) at any time unless approved by Exelixis OR
- Anti-cancer therapy within 4 weeks (with the exception of gefitinib and erlotinib) of the first dose of study drug OR
- Concurrent radiation treatment
Not recovered to NCI CTCAE v.3 Grade ≤1 from significant adverse events due to antineoplastic agents, investigational drugs, or other medications administered prior to study enrollment
Symptomatic or uncontrolled brain metastases requiring current treatment
History of significant hematemesis or recent history of hemoptysis
Presence of cavitation, central lesion, or lesion abutting a major blood vessel
Intercurrent illness such as hypertension or cardiac arrhythmias or recent history of significant disease such as congestive heart failure
Pregnant or breastfeeding
Active bacterial or viral infection requiring systemic treatment
Allergy or hypersensitivity to components of either the XL184 or erlotinib formulations
Incapable of understanding and complying with the protocol or unable to provide informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00596648

Contacts

Contact: Exelixis Contact Line

1-866-939-4041

Locations

United States, Alaska
Katmai Oncology Group	Recruiting
Anchorage, Alaska, United States, 99508
Contact: Ericka Kramer 907-868-8009
Principal Investigator: Jeanne Anderson, MD
United States, California
Stanford University Medical Center	Recruiting
Palo Alto, California, United States, 94305
Contact: Lisa Zhou 650-724-6259 yaya@stanford.edu
Principal Investigator: Heather Wakelee, MD
University of California, Davis	Recruiting
Sacramento, California, United States, 95817
Contact: Corinne Turrell corinne.turrell@ucdmc.ucdavis.edu
Principal Investigator: Primo Lara, MD
United States, Connecticut
Yale University School of Medicine	Recruiting
New Haven, Connecticut, United States, 06520
Contact: Janice Napoletano 203-785-7562 Janice.napoletano@yale.edu
Principal Investigator: Scott Gettinger, MD
United States, District of Columbia
Georgetown University/Lombardi Comprehensive Cancer Center	Recruiting
Washington, District of Columbia, United States, 20007
Contact: Lisa Ley 202-687-6653 leyl@georgetown.edu
Principal Investigator: Deepa Subramaniam, MD
United States, Illinois
University of Chicago Medical Center	Recruiting
Chicago, Illinois, United States, 60637
Contact: Lisa Szeto 773-834-0783 lszeto@medicine.bsd.uchicago.edu
Principal Investigator: Ravi Salgia, MD
United States, Massachusetts
Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Linda Morse 617-632-6949
Principal Investigator: Pasi Janne, MD, PhD
United States, Minnesota
Park Nicollet Institute	Recruiting
St. Louis Park, Minnesota, United States, 55416
Contact: Laura Maybon 952-993-3240 laura.maybon@parknicollet.com
Principal Investigator: Joseph W. Leach, MD
United States, New Jersey
Summit Medical Group	Active, not recruiting
Berkeley Heights, New Jersey, United States, 07922
United States, Ohio
Case Western Reserve University	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Kristi Beatty 216-844-5546
Principal Investigator: Patrick Ma, MD
United States, Texas
MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Deandra (Dee-Dee) Sandles 713-794-1549
Principal Investigator: George Blumenschein, Jr., MD
United States, Washington
Swedish Cancer Institute	Recruiting
Seattle, Washington, United States, 98104
Contact: Heather Reid 206-386-2445 heather.reid@swedish.org
Principal Investigator: Howard West, MD

Sponsors and Collaborators

Exelixis

More Information

No publications provided

Responsible Party:	Exelixis ( John Frye, PharmD )
Study ID Numbers:	XL184-202
Study First Received:	January 8, 2008
Last Updated:	July 22, 2009
ClinicalTrials.gov Identifier:	NCT00596648 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Exelixis:

Lung Cancer
Non-Small-Cell Lung Cancer
NSCLC

Study placed in the following topic categories:

Erlotinib
Thoracic Neoplasms
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases

Non-small Cell Lung Cancer
Protein Kinase Inhibitors
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Thoracic Neoplasms
Erlotinib
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

Carcinoma
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 11, 2009