Study of XL281 in Adults With Solid Tumors

A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL281 Administered Orally to Subjects With Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Cancer; Colorectal Cancer; Non-small-cell Lung Cancer; Papillary Thyroid Cancer
• Intervention / Treatment: Drug: XL281; Drug: famotidine

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Premiere Oncology of Arizona
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75246
      • Mary Crowley Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: Pepcid®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety, tolerability, and maximum tolerated dose (MTD) of once daily or twice daily oral administration of XL281	Assessed at periodic visits
To assess the pharmacokinetic/pharmacodynamic/preliminary clinical activity relationship following XL281 administration in different tumor types from subjects treated at the MTD	Assessed at periodic visits
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	Assessed during the second, third, and fourth week of the first cycle of dosing

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma pharmacokinetics of once daily or twice daily oral administration of XL281	Assessed at periodic visits

Collaborators and Investigators

• Sponsor: Exelixis

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: March 23, 2007
• First Submitted That Met QC Criteria: March 23, 2007
• First Posted (Estimate): March 26, 2007

Study Record Updates

• Last Update Posted (Estimate): October 13, 2011
• Last Update Submitted That Met QC Criteria: October 11, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Cancer; NSCLC; Solid Tumors
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Thyroid Diseases; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Thyroid Neoplasms; Thyroid Cancer, Papillary; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Histamine H2 Antagonists; Famotidine
• Other Study ID Numbers: XL281-001