PS-341 in Treating Patients With Metastatic Kidney Cancer

The University of Chicago

Status and phase: Completed; Phase 2

Conditions: Kidney Cancer

Treatments: Drug: PS-341; Procedure: Tumor Biopsy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00025376

NCI-3291

UCCRC-11049A

11049A

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which regimen of PS-341 is more effective in treating metastatic kidney cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of PS-341 in treating patients who have metastatic kidney cancer.

Full description

OBJECTIVES:

• Determine the objective response rate in patients with metastatic renal cell cancer treated with bortezomib.
• Determine the time to tumor progression and 1-year survival of patients treated with this drug.
• Determine the toxicity profile of this drug in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive bortezomib IV over 3-5 seconds twice weekly on weeks 1 and 2. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo core biopsy.
• Arm II: Patients undergo core biopsy. Patients then receive bortezomib IV as in arm I.

Patients undergo radiologic re-evaluation of measurable lesions. Patients with stable disease or a partial or complete response continue to receive bortezomib in the absence of disease progression or unacceptable toxicity.

Patients are followed for 2 years.

PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 9-14 months.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic renal cell cancer

• Measurable disease

  • At least 2.0 cm in at least 1 dimension by physical exam OR at least 1.0 cm in at least 1 dimension by radiologic exam
  • Single measurable lesion must not be within prior radiotherapy portal

• Tumor lesion amenable to core biopsy

  • At least 1 cm of tumor obtainable

• No active CNS metastatic disease

  • Single previously resected CNS metastasis allowed provided no disease progression 8 weeks after therapy and no longer requiring steroids or antiseizure medications

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Not specified

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• No other uncontrolled concurrent illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier-method contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior immunotherapy or biotherapy allowed

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to 25% or more of bone marrow (i.e., whole pelvis)

Surgery:

• See Disease Characteristics

Other:

• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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23 participants in 2 patient groups

Pre-Treatment biopsy followed by PS-341 administration

Experimental group

Description:

Pre-treatment tumor biopsy followed by 3 cycles of PS-341 given by IV infusion. Each cycle will last 3 weeks. PS-341 will be given 2 times a week for 2 weeks followed by a 'rest' week with no drug. After the 3rd cycle, subjects can continue to receive another 3 cycles of the study drug if their disease has not worsened.

Treatment:

Drug: PS-341

Procedure: Tumor Biopsy

PS-341 administration followed by biopsy

Experimental group

Description:

3 cycles of PS-341 given by IV infusion. Each cycle will last 3 weeks. PS-341 will be given 2 times a week for 2 weeks followed by a 'rest' week with no drug. After the 3rd cycle, subjects will have a tumor biopsy and can continue to receive another 3 cycles of the study drug if their disease has not worsened.

Treatment:

Drug: PS-341

Procedure: Tumor Biopsy