Phase II Trial Of PS-341 (Bortezomib) In Patients With Previously Treated Advanced Urothelial Tract Transitional Cell Carcinoma

NCT ID: NCT00072150

Last Updated: 2013-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-31

Brief Summary

Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. This phase II trial is studying how well bortezomib works in treating patients with advanced transitional cell carcinoma of the urothelium.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the efficacy of PS-341 in patients with measurable advanced urothelial transitional cell carcinoma who have not responded to, or have relapsed after one prior conventional chemotherapy.

II. To determine the safety and toxicity of PS-341 administered in this group of patients.

III. To estimate duration of objective response, progression-free survival and overall survival in this group of patients.

OUTLINE: This is a multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients with a solitary site of disease (i.e., lung or nodal metastases) and who have a partial response (PR) may be considered for surgical resection. Patients with a PR with residual disease after salvage surgery are eligible to continue study therapy. Patients who achieve a complete response, either through resection or bortezomib therapy, receive 2 additional courses of study therapy.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 15-40 patients will be accrued for this study within 13-17 months.

Conditions

Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Stage IV Urethral Cancer; Transitional Cell Carcinoma of the Bladder; Ureter Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (bortezomib)

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients with a solitary site of disease (i.e., lung or nodal metastases) and who have a partial response (PR) may be considered for surgical resection. Patients with a PR with residual disease after salvage surgery are eligible to continue study therapy. Patients who achieve a complete response, either through resection or bortezomib therapy, receive 2 additional courses of study therapy.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

Given IV

Interventions

bortezomib

Given IV

Intervention Type: DRUG

Other Intervention Names

LDP 341; MLN341; VELCADE

Eligibility Criteria

Inclusion Criteria

• Histologic diagnosis of transitional cell carcinoma (TCC) of the bladder, urethra, ureter or renal pelvis; histologic documentation of metastatic/recurrent disease is not required; clinical staging, but not pathological staging, is required
• All patients must have received only one prior systemic chemotherapy regimen for advanced or metastatic disease (which must have included at least one of the following chemotherapy agents: cisplatin, carboplatin, paclitaxel, docetaxel or gemcitabine), with progression documented during or after that treatment; neoadjuvant as well as adjuvant combination chemotherapy is considered a systemic chemotherapy; radiosensitizing single agent chemotherapy is not considered prior systemic therapy
• Patients must have completed radiotherapy (RT) or chemotherapy >= 4 weeks prior to registration on this trial; patients must have recovered from previous treatments or returned to their baseline in the judgment of the enrolling physician
• No Prior treatment with PS-341 or other proteasome inhibitors
• No prior treatment with investigational agents as single agent therapy; however, the incorporation of an investigational agent into the prior systemic chemotherapy regimen is allowed
• Patients must have measurable disease;

• Measurable Disease is defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as >10 mm with spiral CT scan
• Non-measurable disease: Patients with ONLY non-measurable disease are not eligible for this trial

• Nonmeasurable disease is defined as all other lesions, including small lesions (longest diameter <20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions, which include the following:

• Bone lesions;
• Leptomeningeal disease;
• Ascites;
• Pleural/pericardial effusion;
• Inflammatory breast disease;
• Lymphangitis cutis/pulmonis;
• Abdominal masses that are not confirmed and followed by imaging techniques;
• Cystic lesions
• Primary bladder masses
• CTC (ECOG) performance status =< 2
• Patients must have =< grade 1 peripheral neuropathy at baseline
• No known active brain metastases; patients may not have evidence of active brain metastases; screening CT or MRI is not required, unless there is clinical suspicion of brain metastases
• Pregnant and/or nursing women are not eligible for this trial as chemotherapy is thought to present substantial risk to the fetus/infant; men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while in this study; pregnant and/or nursing women are not eligible for this trial as chemotherapy is thought to present substantial risk to the fetus/infant; men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while in this study
• Creatinine =< 2.5 mg/dl or measured or calculated creatinine clearance > 30 ml/min)
• ALT and AST =< 2.5 x ULN
• Total bilirubin =< 1.8 mg/dL
• Granulocytes >= 1500/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 8 g/dl

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan Rosenberg

Role: PRINCIPAL_INVESTIGATOR

Cancer and Leukemia Group B

Locations

UCSF-Mount Zion

San Francisco, California, United States

Countries

United States

Other Identifiers

CALGB-90207

Identifier Type: -

Identifier Source: secondary_id

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02787

Identifier Type: -

Identifier Source: org_study_id