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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00072150

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: bortezomib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2003

Actual Primary Completion Date :

Mar 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: bortezomib Given IV Other Names: LDP 341 MLN341 VELCADE

Arm

Intervention/Treatment

Experimental: 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.

Drug: bortezomib

Given IV

Other Names:

LDP 341

MLN341

VELCADE

Outcome Measures

Primary Outcome Measures

Response rates (CR+PR) determined according to the RECIST criteria [Up to 6 years]
95% confidence intervals will be computed using the binomial distribution.

Secondary Outcome Measures

Duration of objective response [From the date of the first CR or PR to the date that the patient had disease progression (or death), assessed up to 6 years]
The Kaplan-Meier product-limit method will be used to estimate.
Toxicity by type, frequency, and severity [Up to 6 years]
95% confidence intervals for the toxicity rates will be computed using the binomial distribution.
Progression free survival [From the date of initiation of treatment to date of progression or death due to any cause, whichever occurs first, assessed up to 6 years]
The Kaplan-Meier product-limit method will be used to estimate.
Overall survival [From the date of initiation of treatment to date of death due to any cause, assessed up to 6 years]
The Kaplan-Meier product-limit method will be used to estimate.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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