Safety and Pharmacokinetics of XL647 Administered Orally to Subjects With Solid Tumors - Full Text View

Purpose

The primary objective of this study is as follows:

To evaluate the safety and tolerability of XL647 administered orally as a single dose and as repeat doses in subjects with solid tumors.

The secondary objectives of this study are as follows:

To evaluate the plasma pharmacokinetics of XL647 administered orally as a single dose and as repeat doses in subjects with solid tumors,
To estimate renal elimination of XL647 administered orally as a single dose in subjects with solid tumors.

The exploratory objective of this study is as follows:

To assess the pharmacodynamic effects of XL647 administration in plasma and peripheral blood cells.

In addition, subjects may be eligible to enter a Treatment Extension Period. The following information will be obtained from this part of the study:

Long-term safety and tolerability of XL647 after repeat administration,
Tumor response after repeat administration of XL647.

Condition	Intervention	Phase
Cancer	Drug: XL647	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL647 Administered Orally to Subjects With Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Kadmon Corporation, LLC:

Primary Outcome Measures:

To evaluate the safety and tolerability of XL647 administered orally as a single dose and as repeat doses [ Time Frame: First treatment until 30 days post last treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate the plasma pharmacokinetics of XL647 administered orally as a single dose and as repeat dose [ Time Frame: At various time points between pre-treatment and post last treatment ] [ Designated as safety issue: Yes ]
To estimate renal elimination of XL647 administered orally as a single dose in subjects with solid tumors [ Time Frame: At various time points between pre-treatment and post last treatment ] [ Designated as safety issue: Yes ]

Enrollment:	41
Study Start Date:	June 2004
Study Completion Date:	November 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Intervention Details:

Administered orally as a solution with mass-based dosing in early cohorts or as 50-mg tablets at a fixed dose at the MTD. A minimum of 3 subjects was planned for each dosing cohort with dose escalation dependent on subject tolerance of the prior dose. During the Treatment Period, subjects in each cohort were administered a single dose of XL647 on Day 1 followed by a 72-hour period of observation. If there were no XL647-related dose limiting toxicities, subjects received 5 daily doses of XL647 on Days 4-8. Twenty-one days after the initial dose, in the absence of unacceptable toxicity or disease progression, subjects could enter a Treatment Extension Period that consisted of repeated 2-week cycles of five oral doses of XL647 followed by a 9-day observation period.

Other Name: KD019

Eligibility

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

Criteria

Inclusion Criteria:

The subject has a histologically confirmed malignancy that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective,
The subject has disease that is assessable by tumor marker, physical, or radiologic means,
The subject is ≥18 years old,
There have been at least 4 weeks since prior chemotherapy or radiation therapy (6 weeks if the last treatment regimen included BCNU or mitomycin C),
The subject has an ECOG performance status ≤2 (Karnofsky >60%),
The subject has a life expectancy of ≥3 months,
The subject has normal organ and marrow function (hemoglobin >10g/dL, leukocytes >3,000/mL, absolute neutrophil count >1,500/µL, platelets >100,000/µL, total bilirubin within normal institutional limits of normal,AST (SGOT)/ALT(SGPT) <2.5 times the upper limit of normal, and creatinine within normal limits,
The subject is capable of understanding and complying with the protocol and has signed the informed consent document,
Sexually active subjects (both male and female) must use an accepted method of contraception during the course of the study,
Female subjects of childbearing potential (pre-menopausal) must have a negative pregnancy test.

Exclusion Criteria:

The subject has had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or has not recovered from AEs due to agents administered more than 4 weeks earlier,
The subject has received another investigational agent within 30 days (or 5.5 half-lives) of the first dose of study drug,
The subject has known brain metastases,
The subject has a corrected QT interval (QTc) of >0.44 seconds,
The subject has a history of allergic reactions attributed to aspartame or to any other component in the formulation vehicle,
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 nursing,
The subject is known to be positive for the human immunodeficiency virus (HIV).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086528

Locations

United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Kadmon Corporation, LLC

Investigators

Study Director:

Harold Keer, M.D., Ph.D.

Exelixis, Inc. (Study Sponsor)

More Information

No publications provided

Responsible Party:	Kadmon Corporation, LLC
ClinicalTrials.gov Identifier:	NCT00086528 History of Changes
Other Study ID Numbers:	XL647-001
Study First Received:	July 2, 2004
Last Updated:	October 17, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Kadmon Corporation, LLC:

Solid Tumors

ClinicalTrials.gov processed this record on May 23, 2013