Clinical trial NCT00086528: Safety and Pharmacokinetics of XL647 Administered Orally to Subjects With Solid Tumors
Official title: A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL647 Administered Orally to Subjects With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Solid Tumors
Lead sponsor: Kadmon Corporation, LLC
Sponsor class: INDUSTRY
First posted: 2004-07-07
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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).

Primary outcomes:
measure: To evaluate the safety and tolerability of XL647 administered orally as a single dose and as repeat doses
timeFrame: First treatment until 30 days post last treatment
Secondary outcomes:
measure: To evaluate the plasma pharmacokinetics of XL647 administered orally as a single dose and as repeat dose
timeFrame: At various time points between pre-treatment and post last treatment
measure: To estimate renal elimination of XL647 administered orally as a single dose in subjects with solid tumors
timeFrame: At various time points between pre-treatment and post last treatment
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Exelixis, Inc. (Study Sponsor)
name: Harold Keer, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: 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.