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Study of XL281 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: NCT00451880
Recruitment Status : Completed
First Posted : March 26, 2007
Last Update Posted : October 13, 2011
Information provided by:

Brief Summary:
The purpose of this study is to determine the safest dose of the multiple Raf kinase inhibitor (including c-Raf, B-Raf, and the activated mutant B-RafV600E) XL281, how often it should be taken, and how well subjects with cancer tolerate XL281. This study will also determine how the body reacts to XL281 when it is taken with and without food, and with and without Pepcid (famotidine), a drug that inhibits stomach acid production.

Condition or disease Intervention/treatment Phase
Cancer Non-small-cell Lung Cancer Colorectal Cancer Papillary Thyroid Cancer Melanoma Drug: XL281 Drug: famotidine Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 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 XL281 Administered Orally to Subjects With Solid Tumors
Study Start Date : February 2007
Actual Primary Completion Date : October 2011
Actual Study Completion Date : October 2011

Arm Intervention/treatment
Experimental: Arm 1
XL281 administered once a day
Drug: XL281
Gelatin capsules supplied as 5-, 25-, and 100-mg strengths

Experimental: Arm 2
XL281 administered twice a day
Drug: XL281
Gelatin capsules supplied as 5-, 25-, and 100-mg strengths

Experimental: Arm 3
XL281 administered once a day. Subjects in this arm will be dosed under fed conditions, fasted conditions, and with a concomitant single dose of 40 mg famotidine, during the second, third, and fourth week of the first cycle.
Drug: XL281
Gelatin capsules supplied as 5-, 25-, and 100-mg strengths

Drug: famotidine
single dose, supplied as 20-mg or 40-mg tablets
Other Name: Pepcid®

Primary Outcome Measures :
  1. Safety, tolerability, and maximum tolerated dose (MTD) of once daily or twice daily oral administration of XL281 [ Time Frame: Assessed at periodic visits ]
  2. To assess the pharmacokinetic/pharmacodynamic/preliminary clinical activity relationship following XL281 administration in different tumor types from subjects treated at the MTD [ Time Frame: Assessed at periodic visits ]
  3. To determine the bioavailability of XL281 under fed and fasted conditions, and with or without the concomitant use of a single dose of famotidine in subjects with solid tumors [ Time Frame: Assessed during the second, third, and fourth week of the first cycle of dosing ]

Secondary Outcome Measures :
  1. Plasma pharmacokinetics of once daily or twice daily oral administration of XL281 [ Time Frame: Assessed at periodic visits ]

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

Key Inclusion Criteria:

  • The subject has a histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no therapies known to prolong survival. Subjects treated at the MTD (once- or twice- daily) must have a diagnosis of colorectal cancer, non-small-cell lung cancer (no longer recruiting), melanoma, or papillary thyroid cancer. Certain other eligibility requirements must also be met.
  • The subject is ≥18 years old.
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  • The subject has adequate organ and marrow function.
  • The subject is capable of understanding the protocol and has signed the informed consent document.
  • Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study and for 3 months after study drug discontinuation.
  • Female subjects of childbearing potential must have a negative pregnancy test at screening.
  • The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer, carcinoma in situ of the cervix, or a malignancy diagnosed ≥5 years ago, and has had no evidence of disease for 5 years prior to screening for this study).
  • The subject must meet certain other eligibility requirements.

Key Exclusion Criteria:

  • The subject has received anticancer treatment (eg, chemotherapy, radiotherapy, cytokines, or hormones) within 28 days (6 weeks for nitrosoureas or mitomycin C) before the first dose of study drug.
  • The subject has received treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within a certain amount of time before the first dose of study drug.
  • The subject has received any other investigational agent within 28 days of first dose of XL281.
  • The subject has not recovered to Grade ≤1 from adverse events (AEs) or to within 10% of baseline values due to investigational or other agents administered more than 30 days prior to study enrollment. Some irreversible toxicities from previous treatment may be allowed.
  • The subject requires treatment with antacids (continual treatment), proton pump inhibitors, or H2 receptor antagonists.
  • The subject has a primary brain tumor or known brain metastases.
  • The subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • The subject is pregnant or breastfeeding.
  • The subject is known to be positive for the human immunodeficiency virus (HIV).
  • The subject has an allergy or hypersensitivity to components of the XL281 formulation or to famotidine.
  • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
  • The subject is receiving anticoagulation with warfarin or coumarin-related compounds (low-dose warfarin ≤ 1 mg/day, heparin, and low-molecular weight heparin are permitted)
  • The subject must meet certain other eligibility requirements.

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): NCT00451880

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United States, Arizona
Premiere Oncology of Arizona
Scottsdale, Arizona, United States, 85260
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Cancer Research Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
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Responsible Party: Kanya Rajangam, MD/Senior Manager, Clinical Research, Exelixis, Inc. Identifier: NCT00451880    
Other Study ID Numbers: XL281-001
First Posted: March 26, 2007    Key Record Dates
Last Update Posted: October 13, 2011
Last Verified: October 2011
Keywords provided by Exelixis:
Solid Tumors
Additional relevant MeSH terms:
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Thyroid Neoplasms
Thyroid Cancer, Papillary
Neoplasms by Site
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases
Adenocarcinoma, Papillary
Neoplasms, Glandular and Epithelial
Anti-Ulcer Agents
Gastrointestinal Agents
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs