MDACC Study Summary 2005-0396

Study Summary
No. 2005-0396:.......Advanced Cancers......Razelle Kurzrock......Investigational Cancer Therapeutics

Study Summary Title



Study Summary Number:	2005-0396

Study Title:	Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of XL184 Administered Orally to Subjects with Advanced Malignancies

Physician

New Patient Referral



Name:	Razelle Kurzrock	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Investigational Cancer Therapeutics	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-794-1226 Contact us about clinical trials

General Information



Disease Group:	Advanced Cancers	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:	After completion of the first cycle, patients will return to the clinic approximately every 8 weeks for tumor assessment, on Day 1 of each subsequent cycle, and 30, 90 and 180 days after the last dose of XL184.

Treatment Agents:	XL184	Home Care:	For dosing days 2 - 5 of each repeated treatment cycle, XL184 will be provided for self-administration at home.

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	N/A

Description/
Intervention:

The goal of this clinical research study is to find the highest tolerable dose
of XL184 and the safest and most effective schedule on which it can be given.

You will also be asked to give some additional blood samples that will be used
for pharmacodynamic (PD) and pharmacokinetic (PK) testing. PD and PK testing
are used to look at how the level of study drug in your body may affect the
disease.

If you are enrolled in the maximum tolerated dose part of the study (MTD
Group), the following research tests will also be performed:
Extra blood will be drawn for pharmacogenetic (PGx) testing. PGx testing looks
at how someone's genes may predict whether the study drug can be taken over
long periods of time without unpleasant or dangerous side effects.
Extra blood will be drawn for circulating tumor cell (CTC) testing.
Extra blood will be drawn for biomarker testing. Biomarkers are chemical
"markers" (such as proteins) in the blood/tissue that may be related to your
reaction to the study drug.
DNA from the blood and a leftover tissue from a previous biopsy tissue will be
tested for changes in genes that are believed to be causing the cancer such as
for 2 genes called RET and MET.

These tests may help researchers better understand how cancer responds to
XL184.

Study Objectives / Outcomes

The primary objectives of this study are as follows:

To evaluate the safety and tolerability of oral administration of XL184 to subjects with advanced malignancies
To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of oral administration of XL184.
To evaluate plasma pharmacokinetics (PK) and estimate renal elimination of oral administration of XL184 in subjects with advanced malignancies.

The secondary objectives of this study are as follows:

To evaluate the long-term safety and tolerability of XL184 after oral administration for up to 1 year in subjects with advanced malignancies.
To evaluate tumor response (preliminary antitumor activity) after repeat administration of XL184
To evaluate the pharmacodynamic correlates of XL184 activity

Additional second objectives in the MTD Expanded Cohort are as follows:

To assess the progression-free survival and duration of response in subjects with advanced or recurrent medullary thyroid cancer (MTC)
To further characterize the PK and PD parameters of XL184
To correlate the potential pathway dysfunction of thyroid tumor relevant genes such as RET and BRAF and relevant downstream signaling molecules with clinical outcome.

Exploratory objective of this study is as follows:

To assess the pharmacodynamic effect of XL184 in biological samples

Study Status Information



Study Activation / Registration Date:	09/19/2005

IRB Review and Approval Date:	07/20/2005

Study Type:	Therapeutic

Recruitment Status:	Closed

Projected Accrual:	85

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) The subject has a histologically confirmed solid tumor that is metastatic or unresectable and is no longer responding to therapies known to prolong survival or to other standard therapies, or has disease for which no standard therapy exists.

2) The subject is at least 18 years old.

3) The subject has an ECOG performance status </= 2.

4) The subject has a life expectancy of greater than 3 months.

5) The subject has organ and marrow function as follows: absolute neutrophil count >/= 1500/mm^3, platelets >/= 100,000/mm^3, hemoglobin >/= 9 g/dL, bilirubin </= 1.5 mg/dL, serum creatinine </= 1.5 mg/dL or calculated creatinine clearance >/= 60 mL/min, and ALT and AST </= 2.5 times the upper limit of normal if no liver involvement or </= 5 times the upper limit of normal with liver involvement.

6) In the ACTH stimulation test, the subject has a serum cortisol level >/= 20 micrograms/dL (552 nmol/L) 30 - 90 minutes after injection of ACTH.

7) The subject is capable of understanding and complying with the protocol and has signed the informed consent document.

8) Sexually active subjects (male and femaile) must use acceptable methods of contraception during the course of the study and for 3 months after completion of the study.

9) Female patients of childbearing potential must have a negative pregnancy test at screening. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. Amenorrhea for 12 months must be in the absence of chemotherapy, antiestrogens, or ovarian suppression.

10) In addition to complying with the above criteria, subjects in the daily dose capsule MTD Expanded Cohort: i) include at least 20 subjects with metastatic and/or locally advanced or locally recurrent MTC not appropriate for surgical resection; ii) have measurable disease as defined by RECIST criteria; and iii) provide 15 unstained slides of archival tumor tissue or paraffin block. If 15 unstained slides are not available, the subject may be enrolled following a discussion with the sponsor.

Exclusion Criteria:

1) The subject has received chemotherapy or immunotherapy within 4 weeks or has received nitrosoureas or mitomycin C within 6 weeks before the scheduled first dose of XL184 and has not recovered from toxicity (i.e back to baseline or Grade </= 1).

2) The subject has received radiation within 4 weeks of XL184 treatment.

3) The subject has received an investigational drug within 30 days of the first dose of XL184.

4) The subject has not recovered to grade </= 1 from AEs due to investigational drugs or other medications that were administered more than 4 weeks before study enrollment.

5) The subject has known brain metastases.

6) The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

7) The subject is pregnant or breastfeeding.

8) The subject is known to be positive for the human immunodeficiency virus.

9) The subject has an inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.

10) The subject has a known allergy or hypersensitivity to any of the components of the XL184 formulation.

Links

Registration Number: NCT00215605
Study Information on Clinical Trials Registry (clinicaltrials.gov)