Study of XL281 in Adults With Solid Tumors

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00451880
• Other study ID #: XL281-001
• Status: Completed
• Phase: Phase 1
• First received: March 23, 2007
• Last updated: October 11, 2011
• Start date: February 2007
• Est. completion date: October 2011

Study information

• Verified date: October 2011
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Melanoma
• Non-small-cell Lung Cancer
• Papillary Thyroid Cancer
• Thyroid Neoplasms

Intervention

Drug:
• XL281
Gelatin capsules supplied as 5-, 25-, and 100-mg strengths
• famotidine
single dose, supplied as 20-mg or 40-mg tablets

Locations

Country	Name	City	State
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Premiere Oncology of Arizona	Scottsdale	Arizona
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety, tolerability, and maximum tolerated dose (MTD) of once daily or twice daily oral administration of XL281		Assessed at periodic visits	Yes
Primary	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	No
Primary	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	No
Secondary	Plasma pharmacokinetics of once daily or twice daily oral administration of XL281		Assessed at periodic visits	No