Safety Study of Pharmacokinetics of XL888 in Adults With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00796484
Recruitment Status : Terminated (Sponsor decision)
First Posted : November 24, 2008
Last Update Posted : August 21, 2015
Information provided by (Responsible Party):

Brief Summary:
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 or disease Intervention/treatment Phase
Cancer Drug: XL888 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL888 in Subjects With Solid Tumors
Study Start Date : November 2008
Actual Primary Completion Date : November 2010
Actual Study Completion Date : November 2010

Arm Intervention/treatment
Experimental: 1 Drug: XL888
Administered orally

Primary Outcome Measures :
  1. 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 ]
  2. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Estimate renal elimination of XL888 [ Time Frame: Assessed during the first cycle after three weeks of dosing ]
  3. Exploratory: To evaluate preliminary antitumor activity of XL888 [ Time Frame: Assessed every eight weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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.
  2. 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.
  3. The subject is ≥ 18 years old.
  4. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  5. The subject's weight is ≥ 40 kg.
  6. The subject has adequate organ and marrow function.
  7. The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  8. 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.
  9. Female subjects of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
  4. The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation.
  5. The subject has not recovered from clinically-meaningful toxicity due to prior therapy.
  6. The subject has been previously treated with an HSP90 inhibitor
  7. The subject has untreated or uncontrolled brain metastases or evidence of leptomeningeal involvement of disease.
  8. The subject is currently receiving anticoagulation with therapeutic dose of warfarin.
  9. 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.
  10. The subject has a baseline corrected QT interval (QTc) > 460 ms.
  11. The subject is pregnant or breastfeeding.
  12. The subject is known to be positive for the human immunodeficiency virus (HIV).
  13. The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00796484

United States, Pennsylvania
Hospital of the University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States, 78229
Sponsors and Collaborators

Responsible Party: Exelixis Identifier: NCT00796484     History of Changes
Other Study ID Numbers: XL888-001
First Posted: November 24, 2008    Key Record Dates
Last Update Posted: August 21, 2015
Last Verified: August 2015

Keywords provided by Exelixis:
Solid Tumors