MDACC Study Summary 2006-0014

Study Summary
No. 2006-0014:.......Bladder......Arlene Siefker-Radtke......Genitourinary Medical Oncology

Study Summary Title



Study Summary Number:	2006-0014

Study Title:	Phase I Two-Dimensional Dose-Finding Study of Bortezomib in Combination with Gemcitabine/Doxorubicin in Metastatic Surgically Unresectable Urothelial Cancer or Other Solid Tumors.

Physician

New Patient Referral



Name:	Arlene Siefker-Radtke	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Genitourinary Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2830 Contact us about clinical trials

General Information



Disease Group:	Bladder	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:	Approximately every 2 weeks while on chemotherapy.

Treatment Agents:	Bortezomib Doxorubicin Gemcitabine	Home Care:	None

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	Chemotherapy will be given as an outpatient.


Description/ Intervention:	The goal of this clinical research study is to find the highest tolerable dose of Gemzar® (gemcitabine) and Adriamycin® (doxorubicin) that can be given together with Velcade® (bortezomib) in patients with urothelial cancer or other solid tumors.

Study Objectives / Outcomes

Primary Objective
· Find dose pairs of Bortezomib & Gemcitabine/Doxorubicin that have acceptable posterior probability of toxicity (target 30%).

Secondary Objectives

· Define the dose limiting toxicities of the dose pairs found.
· Choose a dose pair (an "MTD") for a future phase II expansion with patients having locally advanced or metastatic urothelial cancer.
· Correlate extent of 20S inhibition with pharmacodynamic markers of p53 pathway activation, including p21 and TRAIL receptor DR5, in peripheral blood mononuclear cells (PBMCs).

Study Status Information



Study Activation / Registration Date:	09/28/2006

IRB Review and Approval Date:	03/01/2006

Study Type:	Phase I

Recruitment Status:	Closed

Projected Accrual:	N/A

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) Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

2) Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie: a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.

3) All patients must: Have biopsy proven cancer (i.e. solid tumor) for which there is no standard therapy available. If prior history of ischemic heart disease or exposure to > 200 mg/m^2 of doxorubicin, patients must have a measured ejection fraction (either by MUGA, ECHO or ventriculography) of at least 45%. Have preserved hepatic function as shown by AST (SGOT) levels < 2 x the upper limit of normal and an INR (for patients NOT on anticoagulant therapy) of < 1.4. Have normal serum creatinine (<=1.5) or creatinine clearance (measured by Cockroft-Gault formula) of >= 20 ml/min.

4) All patients must have measurable or evaluable disease. In general, liver and lung lesions should be at least 1 cm, and patients with node-only disease should have lesions of >/= 1.5 cm in greatest dimension. Patients with disease confined to bone may be eligible of a measurable lytic defect is present or a serum marker is elevated (>4 x ULN). The Study Chairman is the final arbiter in questions related to measurability. Patients with a three-dimensional mass or pelvic sidewall fixation on bladder examination under anesthesia are considered to have measurable disease.

5) For the second stage of the Phase I trial, all patients must have histologic demonstration of metastatic or locally unresectable transitional cell carcinoma of the urothelium. Minor components (<50% overall) of variant such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or small cell change are acceptable. However, when these atypical histologies are dominant, other treatment approaches may be more appropriate, and such patients are not eligible.

6) Zubrod performance status </= 2.

7) Patients must have had at least one prior therapy to be eligible for either the first or second stage a) Patients are eligible with any number of prior regimens regardless of what those regimens contained (i.e. prior Bortezomib or combination gemcitabine and adriamycin is acceptable).

Exclusion Criteria:

1) Patient has a platelet count of < 100 x 10^9/L.

2) Patient has an absolute neutrophil count of < 1.2 x 10^9/L.

3) Patient has >/= Grade 2 peripheral neuropathy within 14 days before enrollment.

4) Patient has total bilirubin > 2.5 mg/dL.

5) Patient has hypersensitivity to bortezomib, boron, mannitol, gemcitabine, or doxorubicin. Gemcitabine skin rash that be controlled by short course steroids is allowed.

6) Female subject is pregnant or breast-feeding.

7) Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test (Unless there is reasonable certainty that beta-hCG is coming from the tumor). Pregnancy testing is not required for post-menopausal or surgically sterilized women.

8) Patient has received other investigational drugs with 14 days before enrollment.

9) Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

10) Patients with significant atherosclerotic disease, as defined by: a) Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia or active conduction system abnormalities. Any prior ECG abnormality at Screening has to be documented by the investigator as not medically relevant. b) Symptomic congestive heart failure. c) Claudication limiting activity and d) History of cerebrovascular events within the last year (including TIA).

11) Patient have uncontrolled brain metastases or central nervous system disease.

12) Patients with an active, or likely to become active second malignancy.

13) Patients must be at least 6 weeks out from pelvic irradiation, and must not have more than 10% of bone marrow irradiated.

Links

Registration Number: NCT00479128
Study Information on Clinical Trials Registry (clinicaltrials.gov)