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

Stage IV Bladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00072150
• Other study ID #: NCI-2012-02787
• Secondary ID: CALGB-90207U10CA
• Status: Completed
• Phase: Phase 2
• First received: November 4, 2003
• Last updated: June 4, 2013
• Start date: October 2003

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• 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
• Ureteral Neoplasms
• Urethral Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• bortezomib
Given IV

Locations

Country	Name	City	State
United States	UCSF-Mount Zion	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rates (CR+PR) determined according to the RECIST criteria	95% confidence intervals will be computed using the binomial distribution.	Up to 6 years	No
Secondary	Duration of objective response	The Kaplan-Meier product-limit method will be used to estimate.	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	No
Secondary	Toxicity by type, frequency, and severity	95% confidence intervals for the toxicity rates will be computed using the binomial distribution.	Up to 6 years	Yes
Secondary	Progression free survival	The Kaplan-Meier product-limit method will be used to estimate.	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	No
Secondary	Overall survival	The Kaplan-Meier product-limit method will be used to estimate.	From the date of initiation of treatment to date of death due to any cause, assessed up to 6 years	No