Bortezomib With Gemcitabine/Doxorubicin in Patients With Urothelial Cancer and Other Solid Tumors

NCT00479128 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2006-0014NCI-2019-06147
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor; Urethral Cancer

Keywords

Solid Tumor; Bladder Cancer; Ureteral Cancer; Urothelial Cancer; Urethral Cancer; Renal Pelvis Tumor; Bortezomib; Gemcitabine; Doxorubicin; Gemzar; Adriamycin; Velcade; LDP-341; MLN341; PS-341; Gemcitabine Hydrochloride; AD; Hydroxydaunomycin hydrochloride

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Gemzar + Adriamycin Given with Velcade

  Prior to each 2 week cycle

Secondary Outcomes (1)

• Response of Gemzar + Adriamycin Given with Velcade

  42 days

Study Arms (1)

Bortezomib + Gemcitabine + Doxorubicin

EXPERIMENTAL

Starting dose of Bortezomib 0.8 mg/m\^2 IV Over 3-5 Seconds. Starting dose of Gemcitabine 225 mg/m\^2 IV Up to 90 Minutes. Starting dose of Doxorubicin 12.5 mg/m\^2 IV Over 15-30 minutes.

Drug: Bortezomib; Drug: Gemcitabine; Drug: Doxorubicin

Interventions

Bortezomib DRUG

Starting dose: 0.8 mg/m\^2 IV Over 3-5 Seconds

Also known as: Velcade, LDP-341, MLN341, PS-341

Bortezomib + Gemcitabine + Doxorubicin

Gemcitabine DRUG

Starting dose: 225 mg/m\^2 IV Up to 90 Minutes

Also known as: Gemzar, Gemcitabine Hydrochloride

Bortezomib + Gemcitabine + Doxorubicin

Doxorubicin DRUG

Starting dose: 12.5 mg/m\^2 IV Over 15-30 minutes

Also known as: Adriamycin, AD, Hydroxydaunomycin hydrochloride

Bortezomib + Gemcitabine + Doxorubicin

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• 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.
• 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 Cockcroft -Gault formula) of \>= 20 ml/min.
• 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.
• 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.
• Zubrod performance status \</= 2.
• 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).

You may not qualify if:

• Patient has a platelet count of \< 100 x 10\^9/L.
• Patient has an absolute neutrophil count of \< 1.2 x 10\^9/L.
• Patient has \>/= Grade 2 peripheral neuropathy within 14 days before enrollment.
• Patient has total bilirubin \> 2.5 mg/dL.
• Patient has hypersensitivity to bortezomib, boron, mannitol, gemcitabine, or doxorubicin. Gemcitabine skin rash that be controlled by short course steroids is allowed.
• Female subject is pregnant or breast-feeding.
• 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.
• Patient has received other investigational drugs with 14 days before enrollment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• 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) Symptomatic congestive heart failure. c) Claudication limiting activity and d) History of cerebrovascular events within the last year (including TIA).
• Patient have uncontrolled brain metastases or central nervous system disease.
• Patients with an active, or likely to become active second malignancy.
• Patients must be at least 6 weeks out from pelvic irradiation, and must not have more than 10% of bone marrow irradiated.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Urethral Neoplasms; Urinary Bladder Neoplasms; Ureteral Neoplasms

Interventions

Bortezomib; Gemcitabine; Doxorubicin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urethral Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases; Ureteral Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Arlene Siefker-Radtke, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2007
• First Posted: May 25, 2007
• Study Start: September 28, 2006
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)