Safety and Pharmacokinetics of XL647 Administered Orally to Subjects With Solid Tumors

A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL647 Administered Orally to Subjects With Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: XL647

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

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

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

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).

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and tolerability of XL647 administered orally as a single dose and as repeat doses	First treatment until 30 days post last treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the plasma pharmacokinetics of XL647 administered orally as a single dose and as repeat dose	At various time points between pre-treatment and post last treatment
To estimate renal elimination of XL647 administered orally as a single dose in subjects with solid tumors	At various time points between pre-treatment and post last treatment

Collaborators and Investigators

• Sponsor: Kadmon Corporation, LLC
• Investigators: Study Director: Harold Keer, M.D., Ph.D., Exelixis, Inc. (Study Sponsor)

Publications and helpful links

General Publications

• Das M, Padda SK, Frymoyer A, Molina J, Adjei A, Lensing JL, Miles D, Sikic BI, Wakelee HA. A safety, tolerability, and pharmacokinetic analysis of two phase I studies of multitargeted small molecule tyrosine kinase inhibitor XL647 with an intermittent and continuous dosing schedule in patients with advanced solid malignancies. Cancer Chemother Pharmacol. 2018 Sep;82(3):541-550. doi: 10.1007/s00280-018-3646-0. Epub 2018 Jul 20.

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: July 2, 2004
• First Submitted That Met QC Criteria: July 6, 2004
• First Posted (Estimate): July 7, 2004

Study Record Updates

• Last Update Posted (Actual): May 13, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Solid Tumors
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; XL647
• Other Study ID Numbers: XL647-001