Safety Study of Pharmacokinetics of XL888 in Adults With Solid Tumors - Full Text View

Sponsor:	Exelixis
Information provided by:	Exelixis
ClinicalTrials.gov Identifier:	NCT00796484

Purpose

The purpose of this study is to evaluate the safety and tolerability of XL888 in subjects with solid tumors. XL888 is a potent and selective inhibitor of HSP90, a key component of a molecular chaperone complex that promotes the conformational maturation and stabilization of diverse client proteins. Many HSP90 client proteins play critical roles in signaling pathways implicated in tumor cell growth, proliferation, and survival.

Condition	Intervention	Phase
Cancer	Drug: XL888	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL888 in Subjects With Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Exelixis:

Primary Outcome Measures:

Safety, tolerability, and maximum tolerated dose of oral administration of XL888 when administered on an intermittent schedule to adults with solid tumors [ Time Frame: Assessed at several visits during weeks 1 through 4 of the first cycle and approximately every other week each cycle thereafter ] [ Designated as safety issue: Yes ]
Plasma pharmacokinetics of oral administration of XL888 when administered on an intermittent schedule [ Time Frame: Assessed at several visits during weeks 1 through 4 of the first cycle and approximately once every four weeks each cycle thereafter ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacodynamic effects of XL888 on both tumor tissue and non-tumor tissue [ Time Frame: Assessed at specific visits during the first cycle; mandatory blood samples collected once every four weeks every cycle thereafter with optional tissue samples ] [ Designated as safety issue: No ]
Estimate renal elimination of XL888 [ Time Frame: Assessed during the first cycle after three weeks of dosing ] [ Designated as safety issue: No ]
Exploratory: To evaluate preliminary antitumor activity of XL888 [ Time Frame: Assessed every eight weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	November 2008
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: XL888 Administered orally

Eligibility

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

Criteria

Inclusion Criteria:

Subject has a histologically-confirmed tumor that is metastatic or unresectable and is no longer responding to therapies known to prolong survival or to other standard therapies, or has disease for which no effective therapy exists.
For subjects enrolling in the maximum tolerated dose expansion cohorts:
- Subject has documented evidence of Her2-overexpressing tumor; OR
- Subject has NSCLC that has progressed after a prior response to erlotinib or gefitinib; OR
- Subject has histologically-confirmed, metastatic melanoma.
- For subjects in the expansion cohorts A and C: tumor tissue must be accessible for biopsy and subjects must be willing to undergo tumor biopsy.
The subject is ≥ 18 years old.
The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
The subject's weight is ≥ 40 kg.
The subject has adequate organ and marrow function.
The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
Sexually active subjects (male and female) must use accepted methods of contraception during the course of the study and for 3 months after the last dose of XL888.
Female subjects of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic therapy (cytokines, antibodies) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first dose of XL888.
The subject has received prior treatment with a small molecule kinase inhibitor (including an investigational kinase inhibitor) or hormonal therapy within 14 days before the first dose of XL888.
The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation.
The subject has not recovered from clinically-meaningful toxicity due to prior therapy.
The subject has been previously treated with an HSP90 inhibitor
The subject has untreated or uncontrolled brain metastases or evidence of leptomeningeal involvement of disease.
The subject is currently receiving anticoagulation with therapeutic dose of warfarin.
The subject has uncontrolled intercurrent illness including, but not limited to: ongoing or active infection; diabetes mellitus; hypertension; symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months.
The subject has a baseline corrected QT interval (QTc) > 460 ms.
The subject is pregnant or breastfeeding.
The subject is known to be positive for the human immunodeficiency virus (HIV).
The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00796484

Contacts

Contact: PRA Contact Line

1-800-251-8124

Locations

United States, Pennsylvania
Hospital of the University of Pennsylvania Abramson Cancer Center	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Amy Kramer 215-662-7013 kramera@uphs.upenn.edu
Principal Investigator: Peter O'Dwyer, MD
United States, Texas
South Texas Accelerated Research Therapeutics	Recruiting
San Antonio, Texas, United States, 78229
Contact: Tracy Dufresne, BSN, RN, OCN, CCRP 210-593-5265 tracy.dufresne@start.stoh.com
Principal Investigator: Kyriakos P. Papadopoulos, MD

Sponsors and Collaborators

Exelixis

More Information

No publications provided

Responsible Party:	Exelixis, Inc. ( Richard Buller, MD/Vice President, Translational Medicine )
Study ID Numbers:	XL888-001
Study First Received:	November 20, 2008
Last Updated:	April 15, 2009
ClinicalTrials.gov Identifier:	NCT00796484 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Exelixis:

Cancer
Solid Tumors

ClinicalTrials.gov processed this record on November 05, 2009