MDACC Study Summary 2007-0187 (Archived)

Study Summary
No. 2007-0187:.......Advanced Cancers; Lymphoma......Razelle Kurzrock......Investigational Cancer Therapeutics

Study Summary Title



Study Summary Number:	2007-0187

Study Title:	A Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL844 Administered as a Single Agent and in Combination with Gemcitabine in 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:	713-563-1930 Contact us about clinical trials

General Information



Disease Group:	Advanced Cancers Lymphoma	Supported By:	Exelixis, Inc.

Phase of Study:	Phase I	Return Visit:	Participants will return on Days 1, 2, 3, 4, and 8 during the single-agent Study Treatment Period; Days 1, 2, 8, and 15 of the Combination Study Treatment Period; Days 1, 8 and 15 of Treatment Extension Period.

Treatment Agents:	Gemcitabine XL844	Home Care:	Participants may self-administer XL844 on Day 9 of Study Treatment Period and on Days 2, 9 and 16 or each Treatment Extension Period.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

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 XL844 that can be given in combination with gemcitabine to patients with
advanced cancer. The safety of XL844 will also be studied.

Researchers will also do pharmacokinetic (PK) and pharmacodynamic (PD) testing
of XL844. PK testing measures the amount of a drug in the body at different
time points. PD testing is used to look at how the level of study drug in your
body may affect the disease.

Study Objectives / Outcomes

The primary objectives of this study are as follows:

To evaluate the safety and tolerability of XL844 as a single agent when orally administered on Days 1, 2, 8, and 9 or Weeks 1 and 2 of Cycle 1A of the Overall Study Treatment Period (Cycle 1) in subjects with advanced malignancies
To evaluate the safety and tolerability of the combination of XL844 and gemcitabine in subjects with advanced malignancies
To determine the combination maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) for XL844 when given daily on two consecutive days alone and in combination with gemcitabine for a 6-week period in subjects with advanced malignancies
To determine the plasma PK and estimate renal elimination of XL844 orally administered daily for two consecutive days as a single agent and in combination with gemcitabine (at up to fifteen different dose levels) in subjects with advanced malignancies.

The exploratory objectives of this study are as follows:

To assess tumor response (preliminary antitumor activity) after repeated administration of XL844 in combination with gemcitabine in subjects with advanced malignancies
To evaluate the pharmacodynamic correlates of XL844 activity in blood (plasma), tumor tissue and hair.
To analyze archival tissue samples for tumor mutation status.

Study Status Information



Study Activation / Registration Date:

IRB Review and Approval Date:	05/21/2007

Study Type:	Phase I

Recruitment Status:	Terminated

Projected Accrual:	63

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 advanced malignancy (solid tumor or lymphoma) 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.

2) The subject has disease that is assessable by tumor marker, physical, or radiologic means.

3) The subject is >/= 18 years old.

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

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; alanine aminotransferase (ALT) and aspartate aminotransferase (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) The subject is capable of understanding the informed consent document and has signed the informed consent document.

7) Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study.

8) Female subjects of childbearing potential must have a negative pregnancy test at screening.

9) If a subject has received more than three prior regimens of cytotoxic chemotherapy, more than two biologic regimens, or more than 3000 cGy to > 25% of his or her bone marrow, the investigator must discuss with the sponsor regarding subject suitability before enrollment.

10) The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer, in situ carcinoma 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).

11) Subjects in the expanded MTD cohort with accessible tumor tissue are agreeable to pre- and post-treatment biopsies. If tumor tissure is not accessible, then archival tissues will be obtained.

Exclusion Criteria:

1) The subject has received anticancer treatment (eg, chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agent, or hormones) within 14 days prior to first dose of study drug.

2) The subject has not recovered to Grade </= 1 from AEs due to investigational agents or other medications administered more than 14 days prior to the first dose of study drug.

3) The subject has received radiation to > 25% of his or her bone marrow within 30 days of XL844 treatment.

4) The subject has a primary brain tumor of known brain metastases.

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

6) The subject is pregnant or breastfeeding.

7) The subject is known to be positive for the human immunodeficiency virus (HIV).

8) The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

9) The subject has a known allergy or hypersensitivity to any of the components of the XL844 formulation or gemcitabine.

Links

Registration Number: NCT00475917
Study Information on Clinical Trials Registry (clinicaltrials.gov)