Study of XL281 in Adults With Solid Tumors

This study has been completed.
Sponsor:
Information provided by:
Exelixis
ClinicalTrials.gov Identifier:
NCT00451880
First received: March 23, 2007
Last updated: October 11, 2011
Last verified: October 2011
  Purpose

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 Intervention Phase
Cancer
Non-small-cell Lung Cancer
Colorectal Cancer
Papillary Thyroid Cancer
Melanoma
Drug: XL281
Drug: famotidine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • Safety, tolerability, and maximum tolerated dose (MTD) of once daily or twice daily oral administration of XL281 [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma pharmacokinetics of once daily or twice daily oral administration of XL281 [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: February 2007
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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®

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00451880

Locations
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
Exelixis
  More Information

No publications provided

Responsible Party: Kanya Rajangam, MD/Senior Manager, Clinical Research, Exelixis, Inc.
ClinicalTrials.gov Identifier: NCT00451880     History of Changes
Other Study ID Numbers: XL281-001
Study First Received: March 23, 2007
Last Updated: October 11, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Exelixis:
Cancer
Solid Tumors
NSCLC

Additional relevant MeSH terms:
Thyroid Neoplasms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Lung Neoplasms
Melanoma
Carcinoma
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on August 26, 2014